Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.

PubMed

Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P

2017-06-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report

PubMed Central

Pottipati, Bhaswanth; Arakeri, Surekha U.; Javalgi, Anita P.

2017-01-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast. PMID:28764176

Male ductal carcinoma in situ presenting as bloody nipple discharge: a case report and literature review.

PubMed

Simmons, Rache M

2002-01-01

Male breast carcinoma accounts for 1% of all diagnosed breast carcinoma. Pure ductal carcinoma in situ in men is extremely rare. Unfortunately, male breast cancer is often diagnosed at a late stage because of the minimal awareness of presenting symptoms by the patient and sometimes by the health care provider. Because of this late presentation, the overall prognosis is less favorable. This case is presented to emphasize the importance of recognizing bloody nipple discharge as a clinical sign of male ductal carcinoma in situ and an opportunity for early diagnosis.

Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ.

PubMed

Obeng-Gyasi, Samilia; Ong, Cecilia; Hwang, E Shelley

2016-06-01

The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.

[A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

PubMed

Yamashita, Yamato; Ishiba, Toshiyuki; Oda, Goshi; Nakagawa, Tsuyoshi; Aburatani, Tomoki; Ogo, Taiichi; Nakashima, Yutaka; Baba, Hironobu; Hoshino, Naoaki; Nishioka, Yoshinobu; Kawano, Tatsuyuki; Itoh, Takashi; Kirimura, Susumu; Kobayashi, Hirotoshi

2017-11-01

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

Ductal Carcinoma In Situ: The Whole Truth.

PubMed

Parikh, Ujas; Chhor, Chloe M; Mercado, Cecilia L

2018-02-01

Ductal carcinoma in situ (DCIS) is a noninvasive malignant breast disease traditionally described as a precursor lesion to invasive breast cancer. With screening mammography, DCIS now accounts for approximately 20% of newly diagnosed cancer cases. DCIS is not well understood because of its heterogeneous nature. Studies have aimed to assess prognostic factors to characterize its risk of invasive potential; however, there still remains a lack of uniformity in workup and treatment. We summarize current knowledge of DCIS and the ongoing controversies.

Mixed ductal‐lobular carcinomas: evidence for progression from ductal to lobular morphology

PubMed Central

McCart Reed, Amy E; Kutasovic, Jamie R; Nones, Katia; Saunus, Jodi M; Da Silva, Leonard; Newell, Felicity; Kazakoff, Stephen; Melville, Lewis; Jayanthan, Janani; Vargas, Ana Cristina; Reid, Lynne E; Beesley, Jonathan; Chen, Xiao Qing; Patch, Anne-Marie; Clouston, David; Porter, Alan; Evans, Elizabeth; Pearson, John V; Chenevix‐Trench, Georgia; Cummings, Margaret C; Waddell, Nicola; Lakhani, Sunil R

2018-01-01

Abstract Mixed ductal–lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent ‘collision’ of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E‐cadherin–catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E‐cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E‐cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E‐cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E‐cadherin. The mechanisms driving the phenotypic change may involve E�

Radiotherapy of Ductal Carcinoma In Situ

PubMed Central

Krug, David; Souchon, Rainer

2015-01-01

Summary Ductal carcinoma in situ (DCIS) is a heterogeneous disease in both its biology and clinical course. In the past, recurrence rates after breast-conserving surgery have been as high as 30% after 10 years. The introduction of mammography screening and advances in imaging have led to an increase in the detection of DCIS. The focus of this review is on the role of radiotherapy in the multidisciplinary treatment, including current developments in hypofractionation and boost delivery, and attempts to define low-risk subsets of DCIS for which the need for adjuvant radiation is repeatedly questioned. PMID:26600762

Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.

PubMed

Sugiyama, Michiko; Hasebe, Takahiro; Shimada, Hiroko; Takeuchi, Hideki; Shimizu, Kyoko; Shimizu, Michio; Yasuda, Masanori; Ueda, Shigeto; Shigekawa, Takashi; Osaki, Akihiko; Saeki, Toshiaki

2015-06-01

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. Copyright © 2015 Elsevier Inc. All rights reserved.

Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.

PubMed

Ricciuti, Biagio; Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

2016-09-01

Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.

Development of ipsilateral chest wall spindle cell carcinoma in a patient with invasive ductal breast carcinoma during postoperative adjuvant therapy: A case report.

PubMed

Li, Kaifu; Kang, Hua; Wang, Yajun; Hai, Tao; Wang, Bixiao

2018-05-01

Metaplastic breast carcinoma (MBC) is rare subtype of breast carcinoma and is regarded as ductal carcinoma that undergoes metaplasia into a glandular growth pattern. Spindle cell carcinoma (SPC) is a subtype of MBC with a predominant spindle cell component. The patient was a 52-year-old female with invasive ductal breast carcinoma who underwent a modified radical mastectomy and an axillary node dissection. A new lump was observed underneath the surgical site between the pectoralis major and pectoralis minor muscles 45 days after the patient underwent sequential postoperative chemotherapy and radiotherapy. It was speculated that the new lesion had developed during postoperative adjuvant therapy. And the new lesion was regarded as a recurrence. We performed a wide dissection of the tumor with negative margins. The pathology of the tumor indicated SPC. Then, the patient received chemotherapy and demonstrated a poor response. Local recurrence and pulmonary metastasis developed shortly afterwards, and the patient succumbed to the disease within 5 months. Local recurrence with metaplastic SPC transformed from invasive ductal breast carcinoma during postoperative chemotherapy and radiotherapy is rare. The failure of subsequent chemotherapy and the progression of disease indicate the aggressive nature of SPC and its decreased sensitivity to chemotherapy and radiotherapy. Further studies must be performed to improve the prognosis of these patients.

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

PubMed

Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

2018-01-01

Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.

PubMed

Rahmani, Maryam; Nili, Fatemeh; Tabibian, Elnaz

2018-04-27

BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.

Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

PubMed

Grimm, Lars J; Ghate, Sujata V; Hwang, E Shelley; Soo, Mary Scott

2017-11-01

The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS). We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded. In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications. Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

PubMed

Zhao, Huan-Yu; Han, Yang; Wang, Jian; Yang, Lian-He; Zheng, Xiao-Ying; Du, Jiang; Wu, Guang-Ping; Wang, En-Hua

2017-06-01

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

Myiasis associated with an invasive ductal carcinoma of the left breast: case study

PubMed Central

Rodrigues, Felipe Tavares; Klemig, Larissa Raquel; Cardozo, Marcos Roberto Pereira; Alves, Paulo Cesar; Aguiar, Valéria Magalhães; Lessa, Claudia Soares

2017-01-01

ABSTRACT Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis. PMID:28591263

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

PubMed Central

Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

2018-01-01

Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor (β 1.566, P 0.0001). The masses with abrupt interface boundary are more likely grade 3 (β 1.524, P 0.001) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade (β 1.146, P 0.04) as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited. PMID:29692540

[Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women].

PubMed

Karpinska-Kaczmarczyk, Katarzyna

2009-01-01

The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node-negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas.

Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast.

PubMed

Serce, Nuran; Gnatzy, Annette; Steiner, Susanne; Lorenzen, Henning; Kirfel, Jutta; Buettner, Reinhard

2012-08-24

Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC). Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis. LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

Determining the roles of the three alcohol dehydrogenases (AdhA, AdhB and AdhE) in Thermoanaerobacter ethanolicus during ethanol formation.

PubMed

Zhou, Jilai; Shao, Xiongjun; Olson, Daniel G; Murphy, Sean Jean-Loup; Tian, Liang; Lynd, Lee R

2017-05-01

Thermoanaerobacter ethanolicus is a promising candidate for biofuel production due to the broad range of substrates it can utilize and its high ethanol yield compared to other thermophilic bacteria, such as Clostridium thermocellum. Three alcohol dehydrogenases, AdhA, AdhB and AdhE, play key roles in ethanol formation. To study their physiological roles during ethanol formation, we deleted them separately and in combination. Previously, it has been thought that both AdhB and AdhE were bifunctional alcohol dehydrogenases. Here we show that AdhE has primarily acetyl-CoA reduction activity (ALDH) and almost no acetaldehyde reduction (ADH) activity, whereas AdhB has no ALDH activity and but high ADH activity. We found that AdhA and AdhB have similar patterns of activity. Interestingly, although deletion of both adhA and adhB reduced ethanol production, a single deletion of either one actually increased ethanol yields by 60-70%.

Apparent diffusion coefficient value of diffusion-weighted imaging for differential diagnosis of ductal carcinoma in situ and infiltrating ductal carcinoma.

PubMed

Ding, Jian-Rong; Wang, Dong-Nv; Pan, Jing-Li

2016-01-01

The present meta-analysis investigated the clinical value of apparent diffusion coefficient (ADC) values in diffusion-weighted imaging (DWI) for differential diagnosis of ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Electronic databases searches were employed to identify relevant scientific literature, and the search results were screened to selected high-quality studies for this meta-analysis. Methodological quality of the enrolled studies was evaluated by quality evaluation of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and its corresponding 95% confidence interval (95% CI) were calculated for DCIS versus IDC category of ADC value using Z test. Our meta-analysis contained a combined total of 1,097 subjects (928 patients with IDC and 169 patients with DCIS) from 9 relevant high-quality cohort studies. Pooled ORs demonstrated that ADC value in IDC patients was significantly lower than DCIS patients. Subgroup analysis stratified by ethnicity indicated a higher ADC value in DCIS patients compared to IDC, in Asian population, but not in Caucasians. Magnetic resonance imaging (MRI) machine type-stratified analysis revealed that the ADC value of DWI obtained from both non- General Electric Company (GE) 1.5T and GE 1.5T machines were highly reliable in the differential diagnosis of DCIS and IDC. Our meta-analysis provides evidence that ADC values in DWI accurately conveys the differences in tumor architecture between IDC and DCIS, which has high clinical value in differentiatal diagnosis of IDC and DCIS. This may lead to improved BC prediction and treatment.

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2006-02-01

will comprise the retrospective study. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability...DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study found that 25% of women had in situ carcinomas, including...DCIS, at their death, although the lifetime risk of developing breast cancer during the same period was only 1% (7). Similarly, only 32% of women

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2007-02-01

DCIS tissues, (ii) TC is associated with tumor stage and (iii) TC in DCIS is associated with breast cancer -free survival. 15. SUBJECT TERMS Ductal...carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study found that 25% of women had in situ carcinomas

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in situ of the Breast

DTIC Science & Technology

2009-02-01

breast cancer -free survival. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16...in 2003 (2,3). However, the fraction of women with DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study...found that 25% of women had in situ carcinomas, including DCIS, at their death, although the lifetime risk of developing breast cancer during the same

Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

PubMed Central

2012-01-01

Background Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC). Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event. PMID:22920283

Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy.

PubMed

Menes, Tehillah S; Kerlikowske, Karla; Lange, Jane; Jaffer, Shabnam; Rosenberg, Robert; Miglioretti, Diana L

2017-01-01

Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. Published risk estimates are based on cohorts that included women whose ADH was diagnosed before widespread use of screening mammograms and did not differentiate between the methods used to diagnose ADH, which may be related to the size of the ADH focus. These risks may overestimate the risk in women with presently diagnosed ADH. To examine the risk of invasive cancer associated with ADH diagnosed using core needle biopsy vs excisional biopsy. A cohort study was conducted comparing the 10-year cumulative risk of invasive breast cancer in 955 331 women undergoing mammography with and without a diagnosis of ADH. Data were obtained from 5 breast imaging registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium. Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Ten-year cumulative risk of invasive breast cancer. The sample included 955 331 women with 1727 diagnoses of ADH, 1058 (61.3%) of which were diagnosed by core biopsy and 635 (36.8%) by excisional biopsy. The mean (interquartile range) age of the women at diagnosis was 52.6 (46.9-60.4) years. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI, 2.0-3.4) times higher than the risk in women with no ADH. Atypical ductal hyperplasia diagnosed via excisional biopsy was associated with an adjusted hazard ratio (HR) of 3.0 (95% CI, 2-4.5) and, via core needle biopsy, with an adjusted HR of 2.2 (95% CI, 1.5-3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI, 4.3%-10.1%) of the women had a diagnosis of invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7%; 95% CI, 3.0%-12.8%) compared with those with ADH diagnosed via core needle biopsy (5%; 95% CI, 2

Expression of EGF and EGFR strongly correlates with metastasis of pancreatic ductal carcinoma.

PubMed

Pryczynicz, Anna; Guzińska-Ustymowicz, Katarzyna; Kemona, Andrzej; Czyzewska, Jolanta

2008-01-01

The epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) gene product have been found to play a role in carcinomas of the stomach, liver, breast, ovary and lungs. Recent reports have indicated that they are also involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastasis. Thirty-six patients with pancreatic ductal carcinoma were analysed with respect to sex, age, histological type, malignancy grade (G), pTN status (pTN), local lymph node involvement and distant metastasis. The tumor levels of EGF, EGFR and c-erbB-2 expression were determined immunohistochemically. Expression of c-erbB-2 was observed in 24/36 cases, EGF in 13/36 cases and EGFR in 18/36 cases. Overexpression of EGF and EGFR was associated with metastasis to lymph nodes and other organs. A correlation was also found between EGF expression and the presence of EGFR in the tumour. The expression of c-erbB-2 protein was not found to correlate with any parameters. EGF and EGFR play a key role in neoplastic spread through lymph node involvement and metastasis to other organs.

Flat epithelial atypia on breast needle core biopsy: a retrospective study with clinical-pathological correlation.

PubMed

Lee, Tsu-Yee Joseph; Macintosh, Rebecca F; Rayson, Daniel; Barnes, Penny J

2010-01-01

There are limited data to guide clinical management when flat epithelial atypia (FEA) is identified in breast needle core biopsies (NCBs). Our objectives were to determine the frequency of malignancy in subsequent breast excisions following NCB diagnosis of FEA, and to characterize the pathological and clinical features of associated tumors. Two hundred and fifty-six breast NCBs from a retrospective search (January 1999-July 2007) were blindly reviewed for FEA/other columnar cell lesions (CCLs). NCBs with co-existing carcinoma were excluded. The study included 211 NCBs: 116 (55%) with CCLs without atypia; 40 (19%) with CCLs with atypical ductal hyperplasia (ADH), 15 (7%) with FEA and 40 (19%) with FEA and ADH; 94 cases had follow-up excisions. Ductal carcinoma in situ and/or invasive carcinoma were present in: 4/26 (15%) excisions with CCLs on NCB, 11/30 (37%) with CCLs + ADH, 1/7 (14%) with FEA alone, and 9/31 (29%) with FEA + ADH. (a) FEA was more frequently seen with ADH, than without ADH in NCBs, (b) FEA and CCLs were more frequently associated with malignancy when with ADH, and (c) tumors excised following NCB diagnosis of FEA+/-ADH had favorable prognostic factors. A conservative excision is warranted following a NCB diagnosis of FEA and ADH, and may be warranted for FEA alone.

Ductal Carcinoma in Situ: Clinical Perspective.

PubMed

Kühn, Thorsten

2010-08-01

Ductal carcinoma is situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of improved screening activities. In contrast to invasive disease, DCIS is a local process with excellent survival rates. Current treatment strategies include surgery, radiotherapy (RT) and anti-hormonal treatment. The selection of an individual risk-adapted therapeutic approach remains controversial. This relates especially to the extent of surgery and the therapeutic index of adjuvant RT and tamoxifen. Several new trials have been published or updated recently that address important clinical issues. There is an urgent need to get more insight into the biological behaviour of different subtypes of DCIS, and develop more targeted and individualized treatment strategies. So far, surgery appears to be the most effective treatment modality. A morphology-based treatment model that allows complete resection of certain DCIS lesions without further adjuvant measures has not been evaluated prospectively and deserves further evaluation.

Dietary patterns and risk of ductal carcinoma of the breast: a factor analysis in Uruguay.

PubMed

Ronco, Alvaro L; De Stefani, Eduardo; Deneo-Pellegrini, Hugo; Boffetta, Paolo; Aune, Dagfinn; Silva, Cecilia; Landó, Gabriel; Luaces, María E; Acosta, Gisele; Mendilaharsu, María

2010-01-01

Breast cancer (BC) shows very high incidence rates in Uruguayan women. The present factor analysis of ductal carcinoma of the breast, the most frequent histological type of this malignancy both in Uruguay and in the World, was conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases with ductal BC and 222 controls with normal mammograms. A factor analysis was conducted using 39 food groups, allowing retention of six factors analyzed through logistic regression in order to obtain odds ratios (OR) associated with ductal BC. The low fat and non-alcoholic beverage patterns were inversely associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty cheese pattern was positively associated (OR=4.17) as well as the fried white meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary risk patterns as those identified by studies not discriminating between histologic type of breast cancer.

Comparison of Microvessel Density with Prognostic Factors in Invasive Ductal Carcinomas of the Breast.

PubMed

Şener, Ebru; Şipal, Sare; Gündoğdu, Cemal

2016-01-01

Angiogenesis plays a key role in tumor growth and metastasis. Determination of microvessel density is the most common technique used to evaluate the amount of the intratumoral angiogenesis in breast cancer. We have aimed to investigate the relationship with tumor angiogenesis and prognostic parameters in breast invasive ductal carcinomas. In this study, a total of 100 invasive ductal carcinoma patients, who were diagnosed at the Department of Pathology, Ataturk University Faculty of Medicine between the years 2003-2008, were re-evaluated. Patient characteristics and clinicopathological findings were obtained from archival records. In the present study, microvessel density was determined by immunohistochemical staining by using anti-CD34 monoclonal antibody in the paraffin blocks. First, the most vascular area was selected in the tumor under a low magnification (40x) by a light microscope and then microvessels were counted under a higher magnification (200x). Patients were classified as low and high microvessel density depending on their microvessel counts. Chi-square test and multivariate linear regression analysis were used for statistical analysis (p≤0.05). We have determined that microvessel density increases as tumor size increases (p=0.001). Microvessel density was higher in patients with at least 10 lymph node metastases compared to those with no metastasis (p=0.05). However, there was no statistically significant difference between microvessel density and other prognostic factors such as histological grade, nuclear grade, patient age, vascular invasion, estrogen, progesterone receptor status, HER2/neu expression. In our study, we have found that microvessel density is associated with tumor size and lymph node metastasis in patients with invasive ductal carcinoma.

Quantitatively characterizing the microstructural features of breast ductal carcinoma tissues in different progression stages by Mueller matrix microscope.

PubMed

Dong, Yang; Qi, Ji; He, Honghui; He, Chao; Liu, Shaoxiong; Wu, Jian; Elson, Daniel S; Ma, Hui

2017-08-01

Polarization imaging has been recognized as a potentially powerful technique for probing the microstructural information and optical properties of complex biological specimens. Recently, we have reported a Mueller matrix microscope by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission-light microscope, and applied it to differentiate human liver and cervical cancerous tissues with fibrosis. In this paper, we apply the Mueller matrix microscope for quantitative detection of human breast ductal carcinoma samples at different stages. The Mueller matrix polar decomposition and transformation parameters of the breast ductal tissues in different regions and at different stages are calculated and analyzed. For more quantitative comparisons, several widely-used image texture feature parameters are also calculated to characterize the difference in the polarimetric images. The experimental results indicate that the Mueller matrix microscope and the polarization parameters can facilitate the quantitative detection of breast ductal carcinoma tissues at different stages.

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

PubMed Central

Mahoney, M. Ellen; Gordon, Eva J.; Rao, Jian Yu; Jin, Yusheng; Hylton, Nola; Love, Susan M.

2014-01-01

Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions Intraductal therapy offers

US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey

PubMed Central

Schwartz, Lisa M; Woloshin, Steven; Sox, Harold C; Fischhoff, Baruch; Welch, H Gilbert

2000-01-01

Objective To determine women's attitudes to and knowledge of both false positive mammography results and the detection of ductal carcinoma in situ after screening mammography. Design Cross sectional survey. Setting United States. Participants 479 women aged 18-97 years who did not report a history of breast cancer. Main outcome measures Attitudes to and knowledge of false positive results and the detection of ductal carcinoma in situ after screening mammography. Results Women were aware that false positive results do occur. Their median estimate of the false positive rate for 10 years of annual screening was 20% (25th percentile estimate, 10%; 75th percentile estimate, 45%). The women were highly tolerant of false positives: 63% thought that 500 or more false positives per life saved was reasonable and 37% would tolerate 10 000 or more. Women who had had a false positive result (n=76) expressed the same high tolerance: 39% would tolerate 10 000 or more false positives. 62% of women did not want to take false positive results into account when deciding about screening. Only 8% of women thought that mammography could harm a woman without breast cancer, and 94% doubted the possibility of non-progressive breast cancers. Few had heard about ductal carcinoma in situ, a cancer that may not progress, but when informed, 60% of women wanted to take into account the possibility of it being detected when deciding about screening. Conclusions Women are aware of false positives and seem to view them as an acceptable consequence of screening mammography. In contrast, most women are unaware that screening can detect cancers that may never progress but feel that such information would be relevant. Education should perhaps focus less on false positives and more on the less familiar outcome of detection of ductal carcinoma in situ. PMID:10856064

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanlioglu, Ahter D.; Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya; Korcum, Aylin F.

2007-11-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, thismore » study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.« less

Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy.

PubMed

Graesslin, O; Antoine, M; Chopier, J; Seror, J Y; Flahault, A; Callard, P; Daraï, E; Uzan, S

2010-02-01

Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery. From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought. VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH). ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Angiogenesis in the Progression of Breast Ductal Proliferations

PubMed Central

Carpenter, Philip M.; Chen, Wen-Pin; Mendez, Aaron; McLaren, Christine E.; Su, Min-Ying

2013-01-01

Angiogenesis, the formation of blood vessels, is necessary for a tumor to grow, but when angiogenesis first appears in the progression of breast ductal carcinomas is unknown. To determine when this occurs, the authors examined microvessel density (MVD) by CD31 and CD105 immunostaining in normal ducts, 32 cases of usual hyperplasia, 19 cases of atypical hyperplasia, and 29 cases of ductal carcinoma in situ (DCIS). Simple hyperplasia had a 22-fold greater MVD than normal ducts (P < .0001). An increase during the progression of ductal changes was highly significant (P < .0001). To determine a possible mechanism, immunohistochemistry for vascular endothelial growth factor (VEGF) was evaluated. VEGF staining intensity of ductal epithelium increased during the progression from normal to hyperplastic to DCIS. This study shows that the first significant increase in angiogenesis occurs very early in the evolution of ductal proliferations as ductal cells become hyperplastic. PMID:19403546

Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.

PubMed

Luong, Truc Thanh; Kim, Eun-Hye; Bak, Jong Phil; Nguyen, Cuong Thach; Choi, Sangdun; Briles, David E; Pyo, Suhkneung; Rhee, Dong-Kwon

2015-01-01

Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ΔadhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ΔadhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma

PubMed Central

Logullo, Angela Flavia; Stiepcich, Mônica Maria Ágata; de Toledo Osório, Cintia Aparecida Bueno; Nonogaki, Sueli; Pasini, Fátima Solange; Rocha, Rafael Malagoli; Soares, Fernando Augusto; Brentani, Maria M

2011-01-01

Aims Fos-related antigen 1 (Fra-1) is a member of the activator protein 1 (AP-1) transcription factor family. Our objective was to evaluate the role of Fra-1 expression in breast carcinoma progression and prognosis. Methods and results Fra-1 expression was investigated by immunohistochemistry in two tissue microarrays containing, respectively, 85 ductal carcinoma in situ (DCIS) and 771 invasive ductal carcinoma (IDC) samples. Staining was observed in the nucleus and cytoplasm of the carcinomas, but only nuclear staining was considered to be positive. Fibroblasts associated with IDC were also Fra-1-positive. The frequency of Fra-1 positivity in IDC (22.8%) was lower than that in DCIS (42.2%). No association was found between Fra-1 and clinico-pathological variables in DCIS. In IDC, Fra-1 expression correlated with aggressive phenotype markers, including: high grade, oestrogen receptor negativity and human epidermal growth factor receptor 2 (HER-2) positivity (P = 0.001, 0.015 and 0.004, respectively), and marginally with the presence of metastasis (P = 0.07). Fra-1 was more frequently positive in basal-like (34%) and in HER-2-positive (38.5%) subtypes than in luminal subtypes. Fra-1 presence did not correlate with survival. Conclusions A high frequency of Fra-1 in DCIS tumours may be associated with early events in breast carcinogenesis. Although Fra-1 expression correlated with features of a more aggressive phenotype in IDC, no relationship with overall survival was found. PMID:21371080

Multiphoton microscopic imaging of fibrotic focus in invasive ductal carcinoma of the breast

NASA Astrophysics Data System (ADS)

Chen, Sijia; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

2014-11-01

During the proliferation of breast cancer, the desmoplastic can evoke a fibrosis response by invading healthy tissue. Fibrotic focus (FF) in invasive ductal carcinoma (IDC) of the breast had been reported to be associated with significantly poorer survival rate than IDC without FF. As an important prognosis indicator, it's difficult to obtain the exact fibrotic information from traditional detection method such as mammography. Multiphoton imaging based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) has been recently employed for microscopic examination of unstained tissue. In this study, multiphoton microscopy (MPM) was used to image the fibrotic focus in invasive ductal carcinoma tissue. The morphology and distribution of collagen in fibrotic focus can be demonstrated by the SHG signal. Variation of collagen between IDC with and without FF will be examined and further characterized, which may be greatly related to the metastasis of breast cancer. Our result suggested that the MPM can be efficient in identifying and locating the fibrotic focus in IDC. Combining with the pathology analysis and other detecting methods, MPM owns potential in becoming an advanced histological tool for detecting the fibrotic focus in IDC and collecting prognosis information, which may guide the subsequent surgery option and therapy procedure for patients.

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

PubMed

Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

2011-10-01

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2008-02-01

developing breast cancer during the same period was only 1% (7). Similarly, only 32% of women whose DCIS was misdiagnosed as normal, and so did not receive... breast cancer -free survival. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16...tumors in women 40-49 years of age in 2003 (2,3). However, the fraction of women with DCIS who eventually progress to invasive breast cancer is small

Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ.

PubMed

Bankhead, Armand; Magnuson, Nancy S; Heckendorn, Robert B

2007-06-07

A computer simulation is used to model ductal carcinoma in situ, a form of non-invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time.

A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

PubMed

Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

2016-04-01

A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

Large palpable ductal carcinoma in situ is Her-2 positive with high nuclear grade.

PubMed

Monabati, Ahmad; Sokouti, Ali-Reza; Noori, Sadat Noori; Safaei, Akbar; Talei, Abd-Rasul; Omidvari, Shapoor; Azarpira, Negar

2015-01-01

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group with variable clinical presentation. The exact molecular mechanism is not known why some ductal carcinomas may reach to such a large size but still remains in situ. Although, molecular classification of DCIS lesions and nuclear grading are important for identification of more aggressive lesions but it is not sufficient. Our aim was to examine the expression pattern of immunohistochemical (IHC) markers of ER, PR, HER-2 in palpable DCIS lesions and compare with clinicopathological findings. Our center is referral hospital from South of Iran. Samples were obtained from fifty four patients with a diagnosis of palpable DCIS. Equivocal (2+) case in HER-2 IHC testing was more characterized by chromogenic in situ hybridization. The positive frequency of HER2, ER, and PR was 92%, 48%, and 37% respectively. Palpable DCIS lesions were significantly more HER-2 positive (92%). The DCIS cases were more likely to be of high nuclear grade (grade III) and Her-2 positive cases were more likely to be of high nuclear grade than intermediate grade. All ER negative tumors had high nuclear grade. The Her-2 positivity is suggested as the most important factor responsible for marked in situ proliferation and production of palpable mass.

Large palpable ductal carcinoma in situ is Her-2 positive with high nuclear grade

PubMed Central

Monabati, Ahmad; Sokouti, Ali-Reza; Noori, Sadat Noori; Safaei, Akbar; Talei, Abd-Rasul; Omidvari, Shapoor; Azarpira, Negar

2015-01-01

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group with variable clinical presentation. The exact molecular mechanism is not known why some ductal carcinomas may reach to such a large size but still remains in situ. Although, molecular classification of DCIS lesions and nuclear grading are important for identification of more aggressive lesions but it is not sufficient. Our aim was to examine the expression pattern of immunohistochemical (IHC) markers of ER, PR, HER-2 in palpable DCIS lesions and compare with clinicopathological findings. Our center is referral hospital from South of Iran. Samples were obtained from fifty four patients with a diagnosis of palpable DCIS. Equivocal (2+) case in HER-2 IHC testing was more characterized by chromogenic in situ hybridization. The positive frequency of HER2, ER, and PR was 92%, 48%, and 37% respectively. Palpable DCIS lesions were significantly more HER-2 positive (92%). The DCIS cases were more likely to be of high nuclear grade (grade III) and Her-2 positive cases were more likely to be of high nuclear grade than intermediate grade. All ER negative tumors had high nuclear grade. The Her-2 positivity is suggested as the most important factor responsible for marked in situ proliferation and production of palpable mass. PMID:26097582

Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics.

PubMed

Weinfurtner, R Jared; Patel, Bhavika; Laronga, Christine; Lee, Marie C; Falcon, Shannon L; Mooney, Blaise P; Yue, Binglin; Drukteinis, Jennifer S

2015-06-01

Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk histopathologic features at a single institution found an overall upstage rate to malignancy of 14% at surgical excision. All upstaged lesions were associated with atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular hyperplasia alone or with lobular carcinoma in situ were not associated with an upstage to malignancy. The purpose of the present study w as to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS). A retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed. A total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis. MRI-guided breast biopsies yielding high-risk histopathologic features were associated with

Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study

PubMed Central

Catanzaro, Daniele; Schäffer, Alejandro A.; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with Synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID:26353381

Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

PubMed

Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy

PubMed Central

Menes, Tehillah S; Kerlikowske, Karla; Lange, Jane; Jaffer, Shabnam; Rosenberg, Robert; Miglioretti, Diana L.

2017-01-01

Background Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Published risk estimates are based on cohorts that included women diagnosed prior to the widespread use of screening mammograms and do not differentiate between the methods used to diagnose ADH, which may be related to size of the ADH focus. These risks may overestimate the risk of women currently diagnosed with ADH. We sought to examine the risk of invasive cancer associated with ADH diagnosed on core needle biopsy versus excisional biopsy. Design Cohort study comparing ten-year cumulative risk of invasive breast cancer in women undergoing mammography with and without a diagnosis of ADH. Setting Five breast imaging registries that participate in the National Cancer Institute–funded Breast Cancer Surveillance Consortium (BCSC). Participants Women undergoing mammography in the BCSC. Exposure Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Main outcome Ten-year cumulative risk of invasive breast cancer risk. Results The sample included 955,331 women with 1,727 diagnoses of ADH. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI 2.0, 3.4) times higher than risk in women with no ADH. ADH diagnosed via excisional biopsy was associated with an adjusted HR of 3.0 (95% CI 2.0, 4.5), and via core needle biopsy, with an HR of 2.2 (95% CI 1.5, 3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI 4.3, 10.1) of women were diagnosed with invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7 %; 95% CI 3.0, 12.8) compared to those with ADH diagnosed via core needle biopsy (5.0%; 95% CI 2.2, 8.9). Conclusions Current 10-year risks of invasive breast cancer after a diagnosis of ADH may be lower than previously reported. The risk associated

Pathological criteria and practical issues in papillary lesions of the breast - a review.

PubMed

Ni, Yun-Bi; Tse, Gary M

2016-01-01

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized. © 2015 John Wiley & Sons Ltd.

A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma

PubMed Central

Kwag, Hye Rin; Serbo, Janna V.; Korangath, Preethi; Sukumar, Saraswati

2016-01-01

A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma. PMID:26831041

Early Dysregulation of Cell Adhesion and Extracellular Matrix Pathways in Breast Cancer Progression

PubMed Central

Emery, Lyndsey A.; Tripathi, Anusri; King, Chialin; Kavanah, Maureen; Mendez, Jane; Stone, Michael D.; de las Morenas, Antonio; Sebastiani, Paola; Rosenberg, Carol L.

2009-01-01

Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by quantitative real-time PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and extracellular matrix pathways, are dysregulated before invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches. PMID:19700746

Hyperspectral Imaging and K-Means Classification for Histologic Evaluation of Ductal Carcinoma In Situ.

PubMed

Khouj, Yasser; Dawson, Jeremy; Coad, James; Vona-Davis, Linda

2018-01-01

Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spectral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated that wavelengths near 550 nm showed the best differentiation between tissue types. This information was used to train image processing algorithms using supervised and unsupervised data. The K-means method was applied to the hyperspectral data cubes, and successfully detected spectral tissue differences with sensitivity of 85.45%, and specificity of 94.64% with true negative rate of 95.8%, and false positive rate of 4.2%. These results were verified by ground-truth marking of the tissue samples by a pathologist. In the hyperspectral image analysis, the image processing algorithm, K-means, shows the greatest potential for building a semi-automated system that could identify and sort between normal and ductal carcinoma in situ tissues.

Eliminating "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) terminology in clinical breast practice: The cognitive psychology point of view.

PubMed

Pravettoni, Gabriella; Yoder, Whitney R; Riva, Silvia; Mazzocco, Ketti; Arnaboldi, Paola; Galimberti, Viviana

2016-02-01

There is evidence from the literature that the terms "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) should be eliminated in clinical breast cancer practice and replaced with the new "ductal intraepithelial neoplasia" (DIN) and "lobular intraepithelial neoplasia" (LIN) terminology. The main purpose of the present article is to expand on this argument from a cognitive psychology perspective and offer suggestions for further research, emphasizing how the elimination of the term "carcinoma" in "in situ" breast cancer diagnoses has the potential to reduce both patient and health care professional confusion and misperceptions that are often associated with the DCIS and LCIS diagnoses, as well as limit the adverse psychological effects of women receiving a DCIS or LCIS diagnosis. We comment on the recent peer-reviewed literature on the clinical implications and psychological consequences for breast cancer patients receiving a DCIS or LCIS diagnosis and we use a cognitive perspective to offer new insight into the benefits of embracing the new DIN and LIN terminology. Using cognitive psychology and cognitive science in general, as a foundation, further research is advocated in order to yield data in support of changing the terminology and therefore, offer a chance to significantly improve the lives and psychological sequelae of women facing such a diagnosis. Typology: Controversies/Short Commentary. Copyright © 2015 Elsevier Ltd. All rights reserved.

INACTIVATION OF E. COLI PYRUVATE FORMATE-LYASE: ROLE OF AdhE AND SMALL MOLECULES

PubMed Central

Nnyepi, Mbako R.; Peng, Yi; Broderick, Joan B.

2007-01-01

E. coli AdhE has been reported to harbor three distinct enzymatic activities: alcohol dehydrogenase, acetaldehyde-CoA dehydrogenase, and pyruvate formate-lyase (PFL) deactivase. Herein we report on the cloning, expression, and purification of E. coli AdhE, and the re-investigation of its purported enzymatic activities. While both the alcohol dehydrogenase and acetaldehyde-CoA dehydrogenase activities were readily detectible, we were unable to obtain any evidence for catalytic deactivation of PFL by AdhE, regardless of whether the reported cofactors for deactivation (Fe(II), NAD, and CoA) were present. Our results demonstrate that AdhE is not a PFL deactivating enzyme. We have also examined the potential for deactivation of active PFL by small-molecule thiols. Both β-mercaptoethanol and dithiothreitol deactivate PFL efficiently, with the former providing quite rapid deactivation. PFL deactivated by these thiols can be reactivated, suggesting that this deactivation is non-destructive transfer of an H atom equivalent to quench the glycyl radical. PMID:17280641

Impact of microinvasion on breast cancer mortality in women with ductal carcinoma in situ.

PubMed

Sopik, Victoria; Sun, Ping; Narod, Steven A

2018-02-01

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of epithelial cells which is confined within the basement membrane of the mammary ductal-lobular system. It is of interest to determine to what extent the potential to metastasize increases for DCIS patients when the basement membrane is breached (i.e. microinvasion is present). We retrieved the records of 525,395 women who had either first primary DCIS or small (≤ 2.0 cm) node-negative invasive breast cancer in the Surveillance, Epidemiology and End Results (SEER) registries database (1990-2013). For each patient, we extracted information on year of diagnosis, age at diagnosis, tumour size, tumour grade, oestrogen receptor status, use of radiotherapy, type of surgery, cause of death and follow-up time. We classified patients into four groups, according to the size of the invasive component of the primary tumour. We estimated the actuarial rate of breast cancer-specific mortality at ten and 20 years for women in each size category. We identified 161,394 women with pure DCIS, 13,489 women with microinvasive carcinoma (≤ 0.1 cm of invasion), 153,856 women with invasive cancer 0.2-1.0 cm in size and 196,656 women with invasive cancer 1.1-2.0 cm in size. The 20-year actuarial breast cancer-specific mortality rate was 3.8% for women with pure DCIS, was 6.9% for women with microinvasive carcinoma, was 6.8% for women with invasive cancer 0.2-1.0 cm in size and was 12.1% for women with invasive cancer 1.1-2.0 cm in size. The adjusted hazard ratio for death associated with microinvasive carcinoma (vs. pure DCIS) was 2.00 (95% CI 1.76-2.26; p < 0.0001). In terms of prognosis, microinvasive cancer more closely resembles small invasive cancer 0.2-1.0 cm) than pure DCIS. For invasive cancers under 1.0 cm, size has little impact on mortality.

Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast.

PubMed

Catalano, Onofrio Antonio; Daye, Dania; Signore, Alberto; Iannace, Carlo; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Filomena, Mazzeo; Mansi, Luigi; Soricelli, Andrea; Salvatore, Marco; Fuin, Niccolo; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

2017-07-01

The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invasive ductal carcinoma of the breast. Fifty-one women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET/CT and WB-PET/MRI before treatment. A radiologist and a nuclear medicine physician reviewed in consensus the images from the three modalities and searched for occurrence, number and location of metastases. Final staging, according to each technique, was compared. Pathology and imaging follow-up were used as the reference. WB-DWI, WB-PET/CT and WB-PET/MRI correctly and concordantly staged 33/51 patients: stage IIA in 7 patients, stage IIB in 8 patients, stage IIIC in 4 patients and stage IV in 14 patients. WB-DWI, WB-PET/CT and WB-PET/MRI incorrectly and concordantly staged 1/51 patient as stage IV instead of IIIA. Discordant staging was reported in 17/51 patients. WB-PET/MRI resulted in improved staging when compared to WB-PET/CT (50 correctly staged on WB-PET/MRI vs. 38 correctly staged on WB-PET/CT; McNemar's test; p<0.01). Comparing the performance of WB-PET/MRI and WB-DWI (43 correct) did not reveal a statistically significant difference (McNemar test, p=0.14). WB-PET/MRI is more accurate in the initial staging of breast cancer than WB-DWI and WB-PET/CT, however, the discrepancies between WB-PET/MRI and WB-DWI were not statistically significant. When available, WB-PET/MRI should be considered for staging patient with invasive ductal breast carcinoma.

Classification of ductal carcinoma in situ by gene expression profiling.

PubMed

Hannemann, Juliane; Velds, Arno; Halfwerk, Johannes B G; Kreike, Bas; Peterse, Johannes L; van de Vijver, Marc J

2006-01-01

Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples.

Classification of ductal carcinoma in situ by gene expression profiling

PubMed Central

Hannemann, Juliane; Velds, Arno; Halfwerk, Johannes BG; Kreike, Bas; Peterse, Johannes L; van de Vijver, Marc J

2006-01-01

Introduction Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. Methods Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. Results DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. Conclusion Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples. PMID:17069663

Sentinel lymph node biopsy in clinically detected ductal carcinoma in situ.

PubMed

Al-Ameer, Ahmed Yahia; Al Nefaie, Sahar; Al Johani, Badria; Anwar, Ihab; Al Tweigeri, Taher; Tulbah, Asma; Alshabanah, Mohmmed; Al Malik, Osama

2016-04-10

To study the indications for sentinel lymph node biopsy (SLNB) in clinically-detected ductal carcinoma in situ (CD-DCIS). A retrospective analysis of 20 patients with an initial diagnosis of pure DCIS by an image-guided core needle biopsy (CNB) between June 2006 and June 2012 was conducted at King Faisal Specialist Hospital. The accuracy of performing SLNB in CD-DCIS, the rate of sentinel and non-sentinel nodal metastasis, and the histologic underestimation rate of invasive cancer at initial diagnosis were analyzed. The inclusion criteria were a preoperative diagnosis of pure DCIS with no evidence of invasion. We excluded any patient with evidence of microinvasion or invasion. There were two cases of mammographically detected DCIS and 18 cases of CD-DCIS. All our patients were diagnosed by an image-guided CNB except two patients who were diagnosed by fine needle aspiration (FNA). All patients underwent breast surgery, SLNB, and axillary lymph node dissection (ALND) if the SLN was positive. Twenty patients with an initial diagnosis of pure DCIS underwent SLNB, 2 of whom had an ALND. The mean age of the patients was 49.7 years (range, 35-70). Twelve patients (60%) were premenopausal and 8 (40%) were postmenopausal. CNB was the diagnostic procedure for 18 patients, and 2 who were diagnosed by FNA were excluded from the calculation of the underestimation rate. Two out of 20 had a positive SLNB and underwent an ALND and neither had additional non sentinel lymph node metastasis. Both the sentinel visualization rate and the intraoperative sentinel identification rate were 100%. The false negative rate was 0%. Only 2 patients had a positive SLNB (10%) and neither had additional metastasis following an ALND. After definitive surgery, 3 patients were upstaged to invasive ductal carcinoma (3/18 = 16.6%) and 3 other patients were upstaged to DCIS with microinvasion (3/18 = 16.6%). Therefore the histologic underestimation rate of invasive disease was 33%. SLNB in CD-DCIS is

Ductal carcinoma of breast: nuclear grade as a predictor of S-phase fraction.

PubMed

Dabbs, D J

1993-06-01

Nuclear grade (NG) and S-phase fraction (SPF) are established independent prognostic variables for ductal breast carcinomas. Nuclear grade can be assigned by a pathologist in a simple fashion during histopathologic evaluation of the tumor, while SPF requires flow cytometric evaluation of tumor samples. This prospective study was undertaken to determine whether elevated SPF could be predicted from NG alone and how NG and SPF correlate with c-erbB-2 expression. Eighty-two breast carcinomas of ductal type were assigned an NG of low (grade 1 or grade 2) or high (grade 3). S-phase fraction was recorded initially from fresh-frozen tissue samples and was designated as either low SPF (below the value designated as the cutoff for elevated SPF) or high SPF (a value at or greater than the cutoff value). On fresh tissue the NG predicted the range of SPF (low or high) in 89% of cases. Four percent of the cases that did not correlate could definitely be attributed to sample error. The remaining 7% that did not correlate could have been due to sample error, specimen quality, or tumor heterogeneity, as demonstrated by reversal of SPF range as performed on paraffin blocks of tumor. Eighty-eight percent of the tumors positive for c-erbB-2 were NG 3 and 12% were NG 2. All c-erbB-2 tumors were aneuploid. This study demonstrates the importance of carefully assigning NGs on tissue and indicates the importance of reviewing flow cytometric data side by side with histopathologic parameters to detect discrepancies between these two modalities. Careful nuclear grading assignment can accurately predict the range of SPF.

Culturing primary mouse pancreatic ductal cells.

PubMed

Reichert, Maximilian; Rhim, Andrew D; Rustgi, Anil K

2015-06-01

The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). PDAC resembles ductal cells morphologically. To study pancreatic ductal cell (PDC) and pancreatic intraepithelial neoplasia (PanIN)/PDAC biology, it is essential to have reliable in vitro culture conditions. Here we describe a methodology to isolate, culture, and passage PDCs and duct-like cells from the mouse pancreas. It can be used to isolate cells from genetically engineered mouse models (GEMMs), providing a valuable tool to study disease models in vitro to complement in vivo findings. The culture conditions allow epithelial cells to outgrow fibroblast and other "contaminating" cell types within a few passages. However, the resulting cultures, although mostly epithelial, are not completely devoid of fibroblasts. Regardless, this protocol provides guidelines for a robust in vitro culture system to isolate, maintain, and expand primary pancreatic ductal epithelial cells. It can be applied to virtually all GEMMs of pancreatic disease and other diseases and cancers that arise from ductal structures. Because most carcinomas resemble ductal structures, this protocol has utility in the study of other cancers in addition to PDAC, such as breast and prostate cancers. © 2015 Cold Spring Harbor Laboratory Press.

The bifunctional alcohol and aldehyde dehydrogenase gene, adhE, is necessary for ethanol production in Clostridium thermocellum and Thermoanaerobacterium saccharolyticum.

PubMed

Lo, Jonathan; Zheng, Tianyong; Hon, Shuen; Olson, Daniel G; Lynd, Lee R

2015-04-01

Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are anaerobic thermophilic bacteria being investigated for their ability to produce biofuels from plant biomass. The bifunctional alcohol and aldehyde dehydrogenase gene, adhE, is present in these bacteria and has been known to be important for ethanol formation in other anaerobic alcohol producers. This study explores the inactivation of the adhE gene in C. thermocellum and T. saccharolyticum. Deletion of adhE reduced ethanol production by >95% in both T. saccharolyticum and C. thermocellum, confirming that adhE is necessary for ethanol formation in both organisms. In both adhE deletion strains, fermentation products shifted from ethanol to lactate production and resulted in lower cell density and longer time to reach maximal cell density. In T. saccharolyticum, the adhE deletion strain lost >85% of alcohol dehydrogenase (ADH) activity. Aldehyde dehydrogenase (ALDH) activity did not appear to be affected, although ALDH activity was low in cell extracts. Adding ubiquinone-0 to the ALDH assay increased activity in the T. saccharolyticum parent strain but did not increase activity in the adhE deletion strain, suggesting that ALDH activity was inhibited. In C. thermocellum, the adhE deletion strain lost >90% of ALDH and ADH activity in cell extracts. The C. thermocellum adhE deletion strain contained a point mutation in the lactate dehydrogenase gene, which appears to deregulate its activation by fructose 1,6-bisphosphate, leading to constitutive activation of lactate dehydrogenase. Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are bacteria that have been investigated for their ability to produce biofuels from plant biomass. They have been engineered to produce higher yields of ethanol, yet questions remain about the enzymes responsible for ethanol formation in these bacteria. The genomes of these bacteria encode multiple predicted aldehyde and alcohol dehydrogenases which could be

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma

PubMed Central

Murakami, Eriko; Nakanishi, Yoko; Hirotani, Yukari; Ohni, Sumie; Tang, Xiaoyan; Masuda, Shinobu; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao; Yamada, Tsutomu; Nemoto, Norimichi

2016-01-01

Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC. PMID:27917007

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.

PubMed

Murakami, Eriko; Nakanishi, Yoko; Hirotani, Yukari; Ohni, Sumie; Tang, Xiaoyan; Masuda, Shinobu; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao; Yamada, Tsutomu; Nemoto, Norimichi

2016-11-01

Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA , ROCK , mTOR , AKT1 , and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center ( P <0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC ( P <0.05). In IDCs co-expressing RhoA and ROCK , F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK -negative IDCs ( P <0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.

Metastatic prostate adenocarcinoma to the penis: a series of 29 cases with predilection for ductal adenocarcinoma.

PubMed

Ellis, Carla L; Epstein, Jonathan I

2015-01-01

Twenty-nine men with metastatic prostate adenocarcinoma to the penis were identified at our institution between 1993 and 2013. Of the 29 patients, 19 had a prior history of adenocarcinoma of the prostate, and 8 of those had ductal features in the primary lesion. Sixteen of 29 revealed ductal features in the metastasis. Seven of the 8 cases with ductal features in the primary had ductal features in the penile metastasis. Seven penile metastases were proven to be of prostatic origin solely by immunohistochemistry. Three cases were originally misdiagnosed as urothelial carcinoma upon review of the penile lesion. Other variant morphologies in the metastases included sarcomatoid carcinoma, small cell carcinoma, and adenosquamous carcinoma. In summary, prostate carcinoma involving the penis displays ductal features considerably more often than prostate cancer in general. Features that can cause difficulty in recognizing metastatic prostate adenocarcinoma to the penis include the unusual anatomic site for prostate cancer, poor differentiation, an increased prevalence of variant morphology, a long interval from the primary lesion, and, in some cases, no documented history of a primary prostatic lesion. Immunohistochemical analysis should be performed to rule out prostate carcinoma in penile/penile urethral tumors with morphology that differs from typical squamous or urothelial carcinoma. Even in the setting of metastatic disease, there is a critical need for an accurate diagnosis so that the appropriate therapy can be initiated, symptomatic relief can be provided, and long-term survival achieved in some cases, while at the same time avoiding penectomy for a misdiagnosis of a primary penile cancer.

Anal metastasis as the sentinel and isolated presentation of invasive ductal breast carcinoma.

PubMed

Rengifo, C; Titi, S; Walls, J

2016-05-01

Breast cancer currently affects 1 in 8 women in the UK during their lifetime. Common sites for breast cancer metastasis include the axillary lymph nodes, bones, lung, liver, brain, soft tissue and adrenal glands. There is well documented evidence detailing breast metastasis to the gastrointestinal tract but anal metastasis is exceptionally rare. We present the case of a 78-year-old woman with an anal metastasis as the sentinel and isolated presentation of an invasive ductal breast carcinoma. As advances in the treatment of breast cancer improve, and with an ageing and expanding population, there will be an increasing number of cancer survivors, and more of these unusual presentations may be encountered in the future.

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

PubMed

Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

2016-06-02

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. 2016 BMJ Publishing Group Ltd.

MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer.

PubMed

Johnson, Jennifer M; Cotzia, Paolo; Fratamico, Roberto; Mikkilineni, Lekha; Chen, Jason; Colombo, Daniele; Mollaee, Mehri; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Lin, Zhao; Zhan, Tingting; Tuluc, Madalina; Palazzo, Juan; Birbe, Ruth C; Martinez-Outschoorn, Ubaldo E

2017-01-01

Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ ( p < 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 ( p < 0.05). High nuclear grade was associated with higher MCT1 staining ( p < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 ( p < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status ( p < 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using

MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer

PubMed Central

Johnson, Jennifer M.; Cotzia, Paolo; Fratamico, Roberto; Mikkilineni, Lekha; Chen, Jason; Colombo, Daniele; Mollaee, Mehri; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Lin, Zhao; Zhan, Tingting; Tuluc, Madalina; Palazzo, Juan; Birbe, Ruth C.; Martinez-Outschoorn, Ubaldo E.

2017-01-01

Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ (p < 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 (p < 0.05). High nuclear grade was associated with higher MCT1 staining (p < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 (p < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status (p < 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using MCT1

Towards a proteome signature for invasive ductal breast carcinoma derived from label-free nanoscale LC-MS protein expression profiling of tumorous and glandular tissue.

PubMed

Röwer, Claudia; Vissers, Johannes P C; Koy, Cornelia; Kipping, Marc; Hecker, Michael; Reimer, Toralf; Gerber, Bernd; Thiesen, Hans-Jürgen; Glocker, Michael O

2009-12-01

As more and more alternative treatments become available for breast carcinoma, there is a need to stratify patients and individual molecular information seems to be suitable for this purpose. In this study, we applied label-free protein quantitation by nanoscale LC-MS and investigated whether this approach could be used for defining a proteome signature for invasive ductal breast carcinoma. Tissue samples from healthy breast and tumor were collected from three patients. Protein identifications were based on LC-MS peptide fragmentation data which were obtained simultaneously to the quantitative information. Hereby, an invasive ductal breast carcinoma proteome signature was generated which contains 60 protein entries. The on-column concentrations for osteoinductive factor, vimentin, GAP-DH, and NDKA are provided as examples. These proteins represent distinctive gene ontology groups of differentially expressed proteins and are discussed as risk markers for primary tumor pathogenesis. The developed methodology has been found well applicable in a clinical environment in which standard operating procedures can be kept; a prerequisite for the definition of molecular parameter sets that shall be capable for stratification of patients.

Patient age and breast resection weight affect immediate postmastectomy breast reconstruction in ductal carcinoma in situ.

PubMed

Burnier, Pierre; Hudry, Delphine; See, Leslie-Ann; Duvernay, Alain; Roche, Matthieu; Loustalot, Catherine; Zwetyenga, Narcisse; Coutant, Charles

2016-01-01

Mastectomy is necessary for 40% of the ductal carcinoma in situ. If immediate breast reconstruction (IBR) is systematically proposed, 81% of the patients would choose immediate versus delayed breast reconstruction, but the actual IBR rate is only approximately 50% of them. Therefore, the aim of this study was to identify objective characteristics that distinguish the patients who actually underwent IBR from those who did not. Several criteria of 248 patients who have undergone mastectomy for ductal carcinoma were analyzed. Factors studied were age, body mass index, diabetes, tobacco use, and weight of the specimen of resection. The rate of IBR was 43%. An increase in age and weight of the resection specimen, irrespective of the body mass index, was associated with a lower rate of IBR. Thus, an increase of 100 g in the weight of the breast induces a significant reduction of the IBR (33%). In our series, older patients or patients with larger breasts (irrespective of the body mass index) were less likely to undergo IBR. In order to be in line with the patient's desire, the surgeons of our unit should broaden their indications of IBR. The lack of reconstruction of large breasts should certainly be compensated in part with the recent development of free tissue transfers in our unit. 3. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma.

PubMed

Adachi, Yayoi; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Gondo, Noami; Kotani, Haruru; Iwase, Madoka; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Terada, Mitsuo; Horisawa, Nanae; Mori, Makiko; Oze, Isao; Iwata, Hiroji

2018-03-13

Recent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment. A total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group. SLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis. ILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.

Ascidian and amphioxus Adh genes correlate functional and molecular features of the ADH family expansion during vertebrate evolution.

PubMed

Cañestro, Cristian; Albalat, Ricard; Hjelmqvist, Lars; Godoy, Laura; Jörnvall, Hans; Gonzàlez-Duarte, Roser

2002-01-01

The alcohol dehydrogenase (ADH) family has evolved into at least eight ADH classes during vertebrate evolution. We have characterized three prevertebrate forms of the parent enzyme of this family, including one from an urochordate (Ciona intestinalis) and two from cephalochordates (Branchiostoma floridae and Branchiostoma lanceolatum). An evolutionary analysis of the family was performed gathering data from protein and gene structures, exon-intron distribution, and functional features through chordate lines. Our data strongly support that the ADH family expansion occurred 500 million years ago, after the cephalochordate/vertebrate split, probably in the gnathostome subphylum line of the vertebrates. Evolutionary rates differ between the ancestral, ADH3 (glutathione-dependent formaldehyde dehydrogenase), and the emerging forms, including the classical alcohol dehydrogenase, ADH1, which has an evolutionary rate 3.6-fold that of the ADH3 form. Phylogenetic analysis and chromosomal mapping of the vertebrate Adh gene cluster suggest that family expansion took place by tandem duplications, probably concurrent with the extensive isoform burst observed before the fish/tetrapode split, rather than through the large-scale genome duplications also postulated in early vertebrate evolution. The absence of multifunctionality in lower chordate ADHs and the structures compared argue in favor of the acquisition of new functions in vertebrate ADH classes. Finally, comparison between B. floridae and B. lanceolatum Adhs provides the first estimate for a cephalochordate speciation, 190 million years ago, probably concomitant with the beginning of the drifting of major land masses from the Pangea.

Sonographic findings of high-grade and non-high-grade ductal carcinoma in situ of the breast.

PubMed

Park, Ji-Sung; Park, Young-Mi; Kim, Eun-Kyung; Kim, Suk-Jung; Han, Sang-Suk; Lee, Sun-Joo; In, Hyun-Sin; Ryu, Ji-Hwa

2010-12-01

The purpose of this study was to differentiate between high-grade and non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography. From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. Of the 76 lesions, 44 were classified as high--grade and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false-negative findings on sonography (n = 19) showed microcalcifications on mammography. On sonography, masses were more frequently found in non-high-grade (62.5%) than high-grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high-grade and non-high-grade DCIS. Microcalcifications were more common in high-grade (43.2%) than non-high-grade (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P = .023). Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high-grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non-high-grade DCIS.

Enhanced robustness in acetone-butanol-ethanol fermentation with engineered Clostridium beijerinckii overexpressing adhE2 and ctfAB.

PubMed

Lu, Congcong; Yu, Le; Varghese, Saju; Yu, Mingrui; Yang, Shang-Tian

2017-11-01

Clostridium beijerinckii CC101 was engineered to overexpress aldehyde/alcohol dehydrogenase (adhE2) and CoA-transferase (ctfAB). Solvent production and acid assimilation were compared between the parental and engineered strains expressing only adhE2 (CC101-SV4) and expressing adhE2, ald and ctfAB (CC101-SV6). CC101-SV4 showed an early butanol production from glucose but stopped pre-maturely at a low butanol concentration of ∼6g/L. Compared to CC101, CC101-SV6 produced more butanol (∼12g/L) from glucose and was able to re-assimilate more acids, which prevented "acid crash" and increased butanol production, under all conditions studied. CC101-SV6 also showed better ability in using glucose and xylose present in sugarcane bagasse hydrolysate, and produced 9.4g/L solvents (acetone, butanol and ethanol) compared to only 2.6g/L by CC101, confirming its robustness and better tolerance to hydrolysate inhibitors. The engineered strain of C. beijerinckii overexpressing adhE2 and ctfAB should have good potential for producing butanol from lignocellulosic biomass hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

PubMed

Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S

2001-08-01

Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

Rare ADH Variant Constellations are Specific for Alcohol Dependence

PubMed Central

Zuo, Lingjun; Zhang, Heping; Malison, Robert T.; Li, Chiang-Shan R.; Zhang, Xiang-Yang; Wang, Fei; Lu, Lingeng; Lu, Lin; Wang, Xiaoping; Krystal, John H.; Zhang, Fengyu; Deng, Hong-Wen; Luo, Xingguang

2013-01-01

Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7–ADH1C–ADH1B–ADH1A–ADH6–ADH4–ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence. PMID:23019235

Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3

PubMed Central

Turner-Ivey, Brittany; Smith, Ericka L.; Rutkovsky, Alex C.; Spruill, Laura S.; Mills, Jamie N.

2018-01-01

Purpose NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo. Methods We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin. Results Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50 weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ. Conclusions Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene. PMID:28484924

Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.

PubMed

Lee, Sheng-Huang; Chaung, Chen-Rong

2008-09-01

Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.

Upgrade of high-risk breast lesions detected on mammography in the Breast Cancer Surveillance Consortium

PubMed Central

Menes, Tehillah S.; Rosenberg, Robert; Balch, Steven; Jaffer, Shabnam; Kerlikowske, Karla; Miglioretti, Diana L.

2013-01-01

Background Upgrade rates of high-risk breast lesions after screening mammography were examined. Study design The Breast Cancer Surveillance Consortium registry was used to identify all BI-RADS 4 assessments followed by needle biopsies with high-risk lesions. Follow-up was performed for all women. Results High-risk lesions were found in 957 needle biopsies, with excision documented in 53%. Most (N=685) were atypical ductal hyperplasia (ADH), 173 were lobular neoplasia, and 99 were papillary lesions. Upgrade to cancer varied with type of lesion (18% in ADH, 10% in lobular neoplasia and 2% in papillary). In premenopausal women with ADH, upgrade was associated with family history. Cancers associated with ADH were mostly (82%) ductal carcinoma in situ, those associated with lobular neoplasia were mostly (56%) invasive. During further 2 years of follow-up, cancer was documented in 1% of women with follow-up surgery and in 3% with no surgery. Conclusion Despite low rates of surgery, low rates of cancer were documented during follow-up. Benign papillary lesions diagnosed on BI-RADS 4 mammograms among asymptomatic women do not justify surgical excision. PMID:24112677

Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas.

PubMed

Karpińska-Kaczmarczyk, Katarzyna; Kram, Andrzej; Kaczmarczyk, Mariusz; Domagała, Wenancjusz

2009-01-01

The aim of this study was to evaluate associations between seven morphometric parameters of the nucleoli and nuclei of methyl green and pyronin Y (MG-PY) stained tumour cells of invasive ductal breast carcinoma with relapse-free survival (RFS) and overall survival (OS) time. Histological sections from 150 invasive ductal breast cancers were stained with MG-PY and the following parameters were evaluated by computer image analysis: the nucleolar area, long to short nucleolar axis ratio, nucleolar shape parameter assessing the degree of nucleolar roundness, long to short nuclear axis ratio, number of nucleoli in the nucleus and the percentage of the nuclear cross-section surface area occupied by the nucleoli. A statistically significant association between a nucleolar shape polymorphism and the number of nucleoli in the nuclei of tumour cells and the RFS but not OS was found in the entire group of patients as well as patients with axillary lymph node metastases. A higher polymorphism of nucleolar shape and a higher number of nucleoli in the nuclei of breast cancer cells were associated with decreased relapse-free survival (p < 0.05). The remaining morphometric parameters showed no statistically significant association with RFS or OS. The results indicate that morphometry of nucleoli in MG-PY stained histological sections can be useful in the analysis of associations between nucleolar parameters and prognosis of patients with invasive breast cancer.

Incidental unilateral and bilateral ductal carcinoma in situ encountered in the surgical management of young male gynecomastia.

PubMed

Shirah, Bader Hamza; Shirah, Hamza Assad

2016-07-28

The increased risk for malignant tumors associated with male gynecomastia has been well established and many authors have reported cases of concurrent gynecomastia and ductal carcinoma in situ (DCIS) in the same breast. Synchronous bilateral breast cancer in association with gynecomastia is exceptionally rare. We aim to report and evaluate the management outcome of 5 cases of gynecomastia associated with DCIS (1 bilateral and 4 unilateral). A retrospective database analysis of the surgical treatment outcome of 74 male patients who had gynecomastia was done. A bilateral subcutaneous nipple-preserving mastectomy approach was done to all. Histopathology reports were reviewed. 74 patients diagnosed and treated for gynecomastia were included. The incidence rate of gynecomastia in our hospital male patients was 0.17%. The mean age was 22 years, range 17-29 years. Five (6.76%) patients were found in histopathology specimens to have DCIS, 1 patient (23 years old) had bilateral DCIS of low grade, 4 patients had unilateral positive involvement, 3 had right breast DCIS, and 1 had left breast DCIS, and all were of low-grade papillary subtype. The incidence of ductal carcinoma in situ among our series gynecomastia patients was 6.76%. We conclude that gynecomastia is a benign breast disease but recent reports had described malignant variants, mostly DCIS, including 5 young males in our series. Therefore, regardless of the age group, histopathological examination of the resected gynecomastia tissue should be carefully done in all patients. Further evidence-based studies are needed to investigate the optimum management of incidental DCIS in gynecomastia specimens.

Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status.

PubMed

Silverstein, Melvin J; Buchanan, Claire

2003-12-01

As our knowledge of ductal carcinoma in situ (DCIS) continues to evolve, treatment decision-making has become increasingly complex and controversial for both patients and physicians. Treatment options include mastectomy, and breast conservation with or without radiation therapy. Data produced from the randomized clinical trials for DCIS has provided the basis for important treatment recommendations, but are not without limitations. In this article, we review our prospectively collected database consisting of 1036 patients with DCIS treated at the Van Nuys Breast Center and the USC/Norris Comprehensive Cancer Center. We review the use of the USC/Van Nuys Prognostic Index, a clinical algorithm designed to assist physicians in selection of appropriate treatments, and examine the impact of margin status as a sole predictor of local recurrence.

Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

PubMed

Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

2015-05-17

No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study.

PubMed

Allison, Kimberly H; Rendi, Mara H; Peacock, Sue; Morgan, Tom; Elmore, Joann G; Weaver, Donald L

2016-12-01

This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. © 2016 John Wiley & Sons Ltd.

Histologic Features associated with Diagnostic Agreement in Atypical Ductal Hyperplasia of the Breast: Illustrative Cases from the B-Path Study

PubMed Central

Allison, Kimberly H.; Rendi, Mara H.; Peacock, Sue; Morgan, Tom; Elmore, Joann G.; Weaver, Donald L.

2016-01-01

Background Case specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast are poorly understood. Methods Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histologic features which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists’ perceptions of case difficulty, borderline features, or if they would obtain a second opinion were also examined for associations with agreement. Results Of the 2,070 participant interpretations on the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (p < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (p < 0.001). Diagnostic agreement ranged from 10–89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytologic monotony were associated with higher agreement. Lower agreement rates were associated with solid or micro-papillary architecture, borderline cytologic monotony or cases without a diagnostic area that was obvious on low power. Conclusions The results of this study suggest that pathologists frequently recognize the challenge of ADH cases with some cases more prone to diagnostic variability. In addition, there are specific histologic features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID:27398812

Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review.

PubMed

Demoor-Goldschmidt, C; Mahé, M-A; Supiot, S

2018-04-01

Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

PubMed

Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

2013-07-01

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Development of a plasmid-based expression system in Clostridium thermocellum and its use to screen heterologous expression of bifunctional alcohol dehydrogenases (adhEs)

DOE PAGES

Hon, Shuen; Lanahan, Anthony; Tian, Liang; ...

2016-04-22

Clostridium thermocellum is a promising candidate for ethanol production from cellulosic biomass, but requires metabolic engineering to improve ethanol yield. A key gene in the ethanol production pathway is the bifunctional aldehyde and alcohol dehydrogenase, adhE. To explore the effects of overexpressing wild-type, mutant, and exogenous adhEs, we developed a new expression plasmid, pDGO144, that exhibited improved transformation efficiency and better gene expression than its predecessor, pDGO-66. This new expression plasmid will allow for many other metabolic engineering and basic research efforts in C. thermocellum. As proof of concept, we used this plasmid to express 12 different adhE genes (bothmore » wild type and mutant) from several organisms. Ethanol production varied between clones immediately after transformation, but tended to converge to a single value after several rounds of serial transfer. The previously described mutant C. thermocellum D494G adhE gave the best ethanol production, which is consistent with previously published results.« less

Development of a plasmid-based expression system in Clostridium thermocellum and its use to screen heterologous expression of bifunctional alcohol dehydrogenases (adhEs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hon, Shuen; Lanahan, Anthony; Tian, Liang

Clostridium thermocellum is a promising candidate for ethanol production from cellulosic biomass, but requires metabolic engineering to improve ethanol yield. A key gene in the ethanol production pathway is the bifunctional aldehyde and alcohol dehydrogenase, adhE. To explore the effects of overexpressing wild-type, mutant, and exogenous adhEs, we developed a new expression plasmid, pDGO144, that exhibited improved transformation efficiency and better gene expression than its predecessor, pDGO-66. This new expression plasmid will allow for many other metabolic engineering and basic research efforts in C. thermocellum. As proof of concept, we used this plasmid to express 12 different adhE genes (bothmore » wild type and mutant) from several organisms. Ethanol production varied between clones immediately after transformation, but tended to converge to a single value after several rounds of serial transfer. The previously described mutant C. thermocellum D494G adhE gave the best ethanol production, which is consistent with previously published results.« less

Development of a plasmid-based expression system in Clostridium thermocellum and its use to screen heterologous expression of bifunctional alcohol dehydrogenases (adhEs).

PubMed

Hon, Shuen; Lanahan, Anthony A; Tian, Liang; Giannone, Richard J; Hettich, Robert L; Olson, Daniel G; Lynd, Lee R

2016-12-01

Clostridium thermocellum is a promising candidate for ethanol production from cellulosic biomass, but requires metabolic engineering to improve ethanol yield. A key gene in the ethanol production pathway is the bifunctional aldehyde and alcohol dehydrogenase, adhE . To explore the effects of overexpressing wild-type, mutant, and exogenous adhE s, we developed a new expression plasmid, pDGO144, that exhibited improved transformation efficiency and better gene expression than its predecessor, pDGO-66. This new expression plasmid will allow for many other metabolic engineering and basic research efforts in C. thermocellum . As proof of concept, we used this plasmid to express 12 different adhE genes (both wild type and mutant) from several organisms. Ethanol production varied between clones immediately after transformation, but tended to converge to a single value after several rounds of serial transfer. The previously described mutant C. thermocellum D494G adhE gave the best ethanol production, which is consistent with previously published results.

Expression of adhA from different organisms in Clostridium thermocellum.

PubMed

Zheng, Tianyong; Cui, Jingxuan; Bae, Hye Ri; Lynd, Lee R; Olson, Daniel G

2017-01-01

Clostridium thermocellum is a cellulolytic anaerobic thermophile that is a promising candidate for consolidated bioprocessing of lignocellulosic biomass into biofuels such as ethanol. It was previously shown that expressing Thermoanaerobacterium saccharolyticum adhA in C. thermocellum increases ethanol yield.In this study, we investigated expression of adhA genes from different organisms in Clostridium thermocellum . Based on sequence identity to T. saccharolyticum adhA , we chose adhA genes from 10 other organisms: Clostridium botulinum , Methanocaldococcus bathoardescens , Thermoanaerobacterium ethanolicus , Thermoanaerobacter mathranii , Thermococcus strain AN1, Thermoanaerobacterium thermosaccharolyticum , Caldicellulosiruptor saccharolyticus , Fervidobacterium nodosum , Marinitoga piezophila , and Thermotoga petrophila . All 11 adhA genes (including T. saccharolyticum adhA ) were expressed in C. thermocellum and fermentation end products were analyzed. All 11 adhA genes increased C. thermocellum ethanol yield compared to the empty-vector control. C. botulinum and T. ethanolicus adhA genes generated significantly higher ethanol yield than T. saccharolyticum adhA . Our results indicated that expressing adhA is an effective method of increasing ethanol yield in wild-type C. thermocellum , and that this appears to be a general property of adhA genes.

Ductal carcinoma in situ diagnosed using an ultrasound-guided 14-gauge core needle biopsy of breast masses: can underestimation be predicted preoperatively?

PubMed Central

2014-01-01

Purpose: This study was designed to determine the rate of ductal carcinoma in situ (DCIS)underestimation diagnosed after an ultrasound-guided 14-gauge core needle biopsy (US-14G-CNB) of breast masses and to compare the clinical and imaging characteristics between trueDCIS and underestimated DCIS identified following surgical excision. Methods: Among 3,124 US-14G-CNBs performed for breast masses, 69 lesions in 60 patients were pathologically-determined to be pure DCIS. We classified these patients according to the final pathology after surgical excision as those with invasive ductal carcinoma (underestimated group) and those with DCIS (non-underestimated group). We retrospectively reviewed and compared the clinical and imaging characteristics between the two groups. Results: Of the 69 lesions, 21 were shown after surgery to be invasive carcinomas; the rateof DCIS underestimation was 30.4%. There were no statistically significant differences withrespect to the clinical symptoms, age, lesion size, mammographic findings, and ultrasonographic findings except for the presence of abnormal axillary lymph nodes as detected on ultrasound. The lesions in 2 patients in the non-underestimated group (2/41, 4.9%) and 5 patients in the underestimated group (5/19, 26.3%) were associated with abnormal lymph nodes on axillary ultrasound, and the presence of abnormal axillary lymph nodes on ultrasound was tatistically significant (P=0.016). Conclusion: We found a 30.4% rate of DCIS underestimation in breast masses based on a US-14G-CNB. The presence of abnormal lymph nodes as detected on axillary ultrasound may be useful to preoperatively predict underestimation. PMID:24936506

Alcohol dehydrogenase ADH2-1 and ADH2-2 allelic isoforms in the Russian population correlate with type of alcoholic disease.

PubMed

Ogurtsov, Pavel P.; Garmash, Irina V.; Miandina, Galina I.; Guschin, Alexander E.; Itkes, Alexander V.; Moiseev, Valentin S.

2001-09-01

The frequency ADH2-2 allele in the Moscow urban population and a correlation between the ADH2-2 allele, alcoholic dependence without cirrhosis, symptomatic alcoholic cirrhosis and status on hepatitis B and C infection have been studied. One hundred and twenty-three inhabitants of Moscow (50 healthy donors, 36 patients with alcoholic cirrhosis (subdivided into infected and uninfected by HBV and/or HCV) and 37 patients with alcoholic dependence) of a similar age/sex and drinking pattern have been analysed. The frequency of 41% for ADH2-2 allele is characteristic for an urban Moscow population. This value is intermediate between that found for Asian peoples and for Central and Western Europe. There is a negative correlation between the ADH2-2 allele and alcohol misuse (both alcoholic dependence and alcoholic cirrhosis). This correlation is expressed more in alcoholic dependence. In spite of the possession of the ADH2-2 allele (or genotype ADH2-1/2), alcohol misuse increases the risk of cirrhosis. At the same time, positive status for active hepatitis B, C or combined infection B + C (replication markers HBV-DNA or HCV-RNA) increases the risk for symptomatic alcoholic cirrhosis in alcohol abusing patients, independently of ADH2 genotype.

[ADH/D and impulsiveness: Prevalence of impulse control disorders and other comorbidities, in 81 adults with attention deficit/hyperactivity disorder (ADH/D)].

PubMed

Porteret, R; Bouchez, J; Baylé, F J; Varescon, I

2016-04-01

Attention deficit hyperactivity disorder (ADH/D) is a neuropsychological developmental disorder characterized by pervasive and impairing symptoms of inattention, hyperactivity, and impulsivity. Whereas it is well known in children, there is still little information about ADH/D in adults, including prevalence. Indeed, there are actually no epidemiological studies in France, despite the considerable impact of this disorder in a patient's professional and affective life. Moreover, ADH/D rarely stays isolated, and many comorbidities often complicate the diagnostic investigation. It is well known that the so-called ADH/D is composed of two main categories of symptoms (Attentional Disorder/Hyperactiviy Disorder), but Impulsiveness also remains a major symptom. The aim of this study was to evaluate not only the prevalence of Impulse Control Disorders (ICD) but also psychological and addictive comorbidities among adult patients with ADH/D. A total of 100 patients from specialized consultations of adult ADH/D were evaluated in this study, but only 81 were included after presenting all the clinical criteria of ADH/D. We used the DSM IV-T-R for ADH/D, the Minnesota Impulsive Disorders Interview a semi-structured clinical interview assessing impulse control disorders (ICD) (compulsive buying, trichotillomania, compulsive sexual behaviour, kleptomania, pyromania and intermittent explosive disorder), and the Mini International Neuropsychiatric Interview in order to evaluate psychiatric and addictive comorbidities. More than 90 % of the patients met the early apparition criteria of ADH/D (before 7years). More than half of the patients presented a mixed type of ADH/D (both inattentive and hyperactive-impulsive forms): 55.6 % vs 44.4 % for the inattentive type. The vast majority of patients showed a complete form (with a total of 6 or more symptoms out of 9, of inattentive and/or impulsive-hyperactivity category): 93.8 % and only 6.2 % presented a sub-syndromic form of ADH/D (with

Histologic work-up of non-palpable breast lesions classified as probably benign at initial mammography and/or ultrasound (BI-RADS category 3).

PubMed

Gruber, R; Jaromi, S; Rudas, M; Pfarl, G; Riedl, C C; Flöry, D; Graf, O; Sickles, E A; Helbich, T H

2013-03-01

To determine the accuracy of a probably benign assessment of non-palpable breast lesions (BI-RADS category 3) at mammography and/or ultrasound with immediate histological work-up. Stereotactic or ultrasound guided core needle breast biopsy (NBB) was performed to evaluate 288 lesions, which were prospectively assessed as BI-RADS category 3. Imaging findings included 195 masses, 73 calcification cases, 16 focal asymmetries, and four architectural distortion cases. After NBB, patients underwent either open surgical biopsy (OSB) (n=204) or mammographic follow-up (n=84) for at least 24 months. Histological results of NBB were compared with those of OSB. Three of the 288 lesions (1.0%) proved to be malignant at histological work-up, two of them were ductal carcinoma in situ (DCIS) and one of them was an invasive carcinoma. NBB revealed invasive carcinoma in 1/288 (0.35%) and atypical ductal hyperplasia (ADH) in 13/288 (4.5%) lesions. OSB revealed DCIS in 2/204 (1%) and invasive carcinoma in 1/204 (0.5%) lesions. The two DCIS were underestimated as ADH by NBB. The remaining 285 (99%) lesions proved to be benign at OSB or remained stable during follow-up. Confirmed by tissue diagnosis, the low likelihood of malignancy of prospectively assessed probably benign lesions is below the 2% threshold established for BI-RADS category 3. Imaging follow-up is a safe and effective alternative to immediate histological work-up for such lesions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China.

PubMed

Zhang, Guo-Hong; Mai, Rui-Qin; Huang, Bo

2010-12-21

To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the gene-alcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence interval (CI): 2.76-5.67]. Significant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00, 95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

A novel RNase G mutant that is defective in degradation of adhE mRNA but proficient in the processing of 16S rRNA precursor.

PubMed

Wachi, M; Kaga, N; Umitsuki, G; Clark, D P; Nagai, K

2001-12-21

Escherichia coli RNase G, encoded by the rng gene, is involved in both the processing of 16S rRNA precursor and the degradation of adhE mRNA. Consequently, defects in RNase G result in elevation of AdhE levels. Furthermore, the adhR430 mutant strain, DC430, is reported to overproduce the AdhE protein in a manner dependent on the adhC81 mutation. We found that overproduction of AdhE by DC430 was reversed to wild-type levels by introduction of a plasmid carrying the wild-type allele of rng. Mapping by P1-phage-mediated transduction also indicated that a mutation involved in AdhE overproduction was located around the rng region in DC430. DNA sequencing of the rng region revealed that DC430 indeed had a mutation in the rng gene: a G1022 to A transition that caused substitution of Gly341 with Ser and which was named rng430. This lies in the highly conserved region of the RNase E/RNase G family, called high similarity region 2 (HSR2). However, very interestingly, rng430 mutant strains did not accumulate the 16.3S precursor of 16S rRNA unlike rng::cat mutants. We also found that the Rng1 mutant protein, which is truncated in its C-terminal domain encompassing HSR2, exhibited a residual processing activity against the 16S rRNA precursor, when overproduced. These results indicate that the HSR2 of RNase G plays an important role in substrate recognition and/or ribonucleolytic action.

[A case of mucinous noncystic carcinoma of the pancreas].

PubMed

Jung, Jun Young; Song, Moon Hee; Park, Young Sook; Jo, Yun Ju; Kim, Seong Hwan; Jun, Dae-Won; Kim, Dong Hee; Lee, Won Mi

2008-03-01

Mucinous (colloid) carcinoma is defined as pools of stromal extracellular mucin containing scanty, floating carcinoma cells. It is a well-defined entity in breast or large bowel. However, mucinous noncystic carcinoma of the pancreas (MNCC) is uncommon, comprising between 1% and 3% of all carcinomas of the pancreas. In the past, MNCC generally had been categorized together with ordinary ductal adenocarcinoma or misdiagnosed as mucinous cystadenocarcinoma or signet-ring cell carcinoma. The new WHO classification lists MNCC as a variant of ductal adenocarcinoma. Herein, we report a 32-year-old woman with incidentally found pancreatic body mass who underwent subtotal pancreatectomy. She was diagnosed as MNCC histologically.

Ductal carcinoma of the breast in the pacemaker generator's pocket.

PubMed

Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

2009-01-01

Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

ADH1B promotes mesothelial clearance and ovarian cancer infiltration.

PubMed

Gharpure, Kshipra M; Lara, Olivia D; Wen, Yunfei; Pradeep, Sunila; LaFargue, Chris; Ivan, Cristina; Rupaimoole, Rajesha; Hu, Wei; Mangala, Lingegowda S; Wu, Sherry Y; Nagaraja, Archana S; Baggerly, Keith; Sood, Anil K

2018-05-18

Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.

Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery.

PubMed

Langhans, Linnea; Jensen, Maj-Britt; Talman, Maj-Lis M; Vejborg, Ilse; Kroman, Niels; Tvedskov, Tove F

2017-04-01

New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) and to examine whether the risk of reoperation is associated with DCIS or histologic type of the IBC. This nationwide study including women with histologically verified IBC or DCIS having wire-guided BCS performed between January 1, 2010, and December 31, 2013, used data from the Danish National Patient Registry that were cross-checked with the Danish Breast Cancer Group database and the Danish Pathology Register. Reoperation rate after wire-guided BCS in patients with IBC or DCIS. Wire-guided BCS was performed in 4118 women (mean [SD] age, 60.9 [8.7] years). A total of 725 patients (17.6%) underwent a reoperation: 593 were reexcisions (14.4%) and 132 were mastectomies (3.2%). Significantly more patients with DCIS (271 of 727 [37.3%]) than with IBC (454 of 3391 [13.4%]) underwent a reoperation (adjusted odds ratio, 3.82; 95% CI, 3.19-4.58; P < .001). After the first reexcision, positive margins were still present in 97 patients (16.4%). The risk of repeated positive margins was significantly higher in patients with DCIS vs those with IBC (unadjusted odds ratio, 2.21; 95% CI, 1.42-3.43; P < .001). The risk of reoperation was significantly increased in patients with lobular carcinoma vs those with ductal carcinoma (adjusted odds ratio, 1.44; 95% CI 1.06-1.95; P = .02). A total of 202 patients (4.9%) had a subsequent completion mastectomy, but no difference was found in the type of

Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hathout, Lara; Hijal, Tarek; Théberge, Valérie

2013-12-01

Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. Methods and Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. Results: Between 2003 and 2010, 440 patients with DCISmore » underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.« less

Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

PubMed

Hamada, Yoshihiro; Nakayama, Yoshifuku

Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2 cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years. The small-tumor group (n = 20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n = 5) and 15 patients (non-LM group, n = 15) were either alive without recurrence (n = 11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n = 1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group. Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations.

PubMed

Barreau, Béatrice; de Mascarel, Isabelle; Feuga, Caroline; MacGrogan, Gaétan; Dilhuydy, Marie-Hélène; Picot, Véronique; Dilhuydy, Jean-Marie; de Lara, Christine Tunon; Bussières, Emmanuel; Schreer, I

2005-04-01

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic-pathologic correlation allowed to suspect the DCIS "aggressiveness" on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach.

A multiple mediator analysis approach to quantify the effects of the ADH1B and ALDH2 genes on hepatocellular carcinoma risk.

PubMed

Shih, Stephannie; Huang, Yen-Tsung; Yang, Hwai-I

2018-06-01

Previous work suggested a genetic component affecting the risk of hepatocellular carcinoma (HCC) and mediation analyses have elucidated potential indirect pathways of these genetic effects. Specifically, the effects of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes on HCC risk vary based on alcohol consumption habits. However, alcohol consumption may not be the only mediator in the identified pathway: factors related to alcohol consumption may contribute to the same indirect pathway. Thus, we developed a multimediator model to quantify the genetic effects on HCC risk through sequential dichotomous mediators under the counterfactual framework. Our method provided a closed form formula for the mediation effects through different indirect paths, which requires no assumption for the rarity of outcome. In simulation studies of a finite sample, we presented the utility of the method with the variance of the effects estimated using the delta method and bootstrapping. We applied our method to data from participants in Taiwan (580 cases and 3,207 controls) and quantified the mediation effects of single nucleotide polymorphisms (SNPs) in the ADH1B and ALDH2 genes on HCC through alcohol consumption (yes/no) and high alanine transaminase (ALT) levels (greater than or equal to 45 U/L or below 45 U/L). Assuming a dominant risk model, we identified that the SNPs' effects through alcohol consumption is more significant than through ALT levels on HCC risk. This new method provides insight to the magnitude of various casual mechanisms as a closed form solution and can be readily applied in other genomic studies. © 2018 WILEY PERIODICALS, INC.

Clinicopathology Figures and Long-term Effects of Tamoxifen Plus Radiation on Survival of Women with Invasive Ductal Carcinoma and Triple Negative Breast Cancer.

PubMed

Payandeh, Mehrdad; Sadeghi, Masoud; Sadeghi, Edris; Aeinfar, Mehrnoush

2015-01-01

Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in Ductal Breast Carcinoma.

PubMed

Litwin, Monika; Szczepańska-Buda, Anna; Michałowska, Dagmara; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomułkiewicz, Agnieszka; Wojnar, Andrzej; Dzięgiel, Piotr; Witkiewicz, Wojciech

2018-04-01

P-Element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) are involved in epigenetic regulation of gene expression in germline cells. Aberrant expression of piRNA and PIWI proteins have been identified in various types of tumour cells. The aim of this study was to evaluate the expression profiles of PIWI-like protein-1, -2 (PIWIL1 and PIWIL2), their immunohistochemical (IHC) characteristics in ductal breast cancer, and determine their correlation with clinicopathological parameters of this type of cancer. Material for IHC studies comprised of 101 invasive ductal carcinoma (IDC) cases and 31 mastopathy tissues. Frozen fragments of paired tissue specimens (tumour and adjacent non-malignant breast tissue) taken from 55 patients with IDC and 18 samples of mastopathy were used for molecular studies using real-time polymerase chain reaction (RT-PCR). A statistically significantly higher level of PIWIL1 and PIWIL2 was found in IDC compared to mastopathy samples (p≤0.0001). Increased expression of PIWIL1 was correlated with increased PIWIL2 expression in breast cancer tissue. Surprisingly, PIWIL1 mRNA was detected only in cancer and mastopathy, but was not found in most normal breast tissues, although it is noteworthy that the PIWIL2 mRNA level was statistically significantly lower in mastopathy and IDC samples compared to normal breast tissues. Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Genomic features of lobular breast carcinoma

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

Psychosocial distress affecting patients with ductal carcinoma in situ compared to patients with early invasive breast cancer.

PubMed

Sanders, Judith Brown; Loftin, Adam; Seda, Julia S; Ehlenbeck, Chris

2014-12-01

Psychological distress in patients with a diagnosis of ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC) can emanate from perceived risk of recurrence and is accompanied by perceived risk of death from the diseases. These factors can impart a lower quality of life that can result in poorer health outcomes. In addition, inaccurate risk perceptions can have an effect on decision making, psychosocial outcomes, and subsequent health behaviors. The purpose of this study is to assess patients with DCIS and EIBC and their perceived risk of recurrence and perceived risk of dying, and evaluate their outlook for the future, the degree of social support from spouses and significant others of patients who have been diagnosed with DCIS and EIBC, and the relationship to the patient's perceived risk perception of recurrence and dying from the diseases.

Predictors of underestimation of malignancy after image-guided core needle biopsy diagnosis of flat epithelial atypia or atypical ductal hyperplasia.

PubMed

Yu, Chi-Chang; Ueng, Shir-Hwa; Cheung, Yun-Chung; Shen, Shih-Che; Kuo, Wen-Lin; Tsai, Hsiu-Pei; Lo, Yung-Feng; Chen, Shin-Cheh

2015-01-01

Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors of breast malignancy. Management of FEA or ADH after image-guided core needle biopsy (CNB) remains controversial. The aim of this study was to evaluate malignancy underestimation rates after FEA or ADH diagnosis using image-guided CNB and to identify clinical characteristics and imaging features associated with malignancy as well as identify cases with low underestimation rates that may be treatable by observation only. We retrospectively reviewed 2,875 consecutive image-guided CNBs recorded in an electronic data base from January 2010 to December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211 total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147 (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002, increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p = 0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent predictors of underestimation. In univariate analysis of echo-guided CNB (n = 64), mass with calcifications had the highest underestimation rate (p < 0.001). Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR = 1.122, p = 0.040, increase of 1 year) and calcification distribution were significant independent predictors of underestimation. No FEA case in which, complete calcification retrieval was recorded after CNB was upgraded to malignancy. Older age at diagnosis on image-guided CNB was a predictor of malignancy underestimation. Mass with calcifications was more likely to be associated with malignancy, and in cases presenting as calcifications only, segmental distribution or linear shapes were significantly associated with upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted except for FEA diagnosed using mammography-guided CNB with complete calcification

Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.

PubMed

Do, Sung-Im; Yoon, Gun; Kim, Hyun-Soo; Kim, Kyungeun; Lee, Hyunjoo; Do, In-Gu; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

2016-09-01

Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood. We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC. Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease. BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Imprint cytology on microcalcifications excised by vacuum-assisted breast biopsy: a rapid preliminary diagnosis.

PubMed

Fotou, Maria; Oikonomou, Vassiliki; Zagouri, Flora; Sergentanis, Theodoros N; Nonni, Afroditi; Athanassiadou, Pauline; Drouveli, Theodora; Atsouris, Efstratios; Kotzia, Evagelia; Zografos, George C

2007-04-03

To evaluate imprint cytology in the context of specimens with microcalcifications derived from Vacuum-Assisted Breast Biopsy (VABB). A total of 93 women with microcalcifications BI-RADS 3 and 4 underwent VABB and imprint samples were examined. VABB was performed on Fischer's table using 11-gauge Mammotome vacuum probes. A mammogram of the cores after the procedure confirmed the excision of microcalcifications. For the application of imprint cytology, the cores with microcalcifications confirmed by mammogram were gently rolled against glass microscope slides and thus imprint smears were made. For rapid preliminary diagnosis Diff-Quick stain, modified Papanicolaou stain and May Grunwald Giemsa were used. Afterwards, the core was dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine histological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated. According to the pathological examination, 73 lesions were benign, 15 lesions were carcinomas (12 ductal carcinomas in situ, 3 invasive ductal carcinomas), and 5 lesions were precursor: 3 cases of atypical ductal hyperplasia (ADH) and 2 cases of lobular neoplasia (LN). The observed sensitivity and specificity of the cytological imprints for cancer were 100% (one-sided, 97.5% CI: 78.2%-100%). Only one case of ADH could be detected by imprint cytology. Neither of the two LN cases was detected by the imprints. The imprints were uninformative in 11 out of 93 cases (11.8%). There was no uninformative case among women with malignancy. Imprint cytology provides a rapid, accurate preliminary diagnosis in a few minutes. This method might contribute to the diagnosis of early breast cancer and possibly attenuates patients' anxiety.

Metabolite Profiling of adh1 Mutant Response to Cold Stress in Arabidopsis

PubMed Central

Song, Yuan; Liu, Lijun; Wei, Yunzhu; Li, Gaopeng; Yue, Xiule; An, Lizhe

2017-01-01

As a result of global warming, vegetation suffers from repeated freeze-thaw cycles caused by more frequent short-term low temperatures induced by hail, snow, or night frost. Therefore, short-term freezing stress of plants should be investigated particularly in light of the current climatic conditions. Alcohol dehydrogenase (ADH) plays a central role in the metabolism of alcohols and aldehydes and it is a key enzyme in anaerobic fermentation. ADH1 responds to plant growth and environmental stress; however, the function of ADH1 in the response to short-term freezing stress remains unknown. Using real-time quantitative fluorescence PCR, the expression level of ADH1 was analyzed at low temperature (4°C). The lethal temperature was calculated based on the electrolyte leakage tests for both ADH1 deletion mutants (adh1) and wild type (WT) plants. To further investigate the relationship between ADH1 and cold tolerance in plants, low-Mr polar metabolite analyses of Arabidopsis adh1 and WT were performed at cold temperatures using gas chromatography-mass spectrometry. This investigation focused on freezing treatments (cold acclimation group: −6°C for 2 h with prior 4°C for 7 d, cold shock group: −6°C for 2 h without cold acclimation) and recovery (23°C for 24 h) with respect to seedling growth at optimum temperature. The experimental results revealed a significant increase in ADH1 expression during low temperature treatment (4°C) and at a higher lethal temperature in adh1 compared to that in the WT. Retention time indices and specific mass fragments were used to monitor 263 variables and annotate 78 identified metabolites. From these analyses, differences in the degree of metabolite accumulation between adh1 and WT were detected, including soluble sugars (e.g., sucrose) and amino acids (e.g., asparagine). In addition, the correlation-based network analysis highlighted some metabolites, e.g., melibiose, fumaric acid, succinic acid, glycolic acid, and xylose, which

Ethnic Related Selection for an ADH Class I Variant within East Asia

PubMed Central

Li, Hui; Gu, Sheng; Cai, Xiaoyun; Speed, William C.; Pakstis, Andrew J.; Golub, Efim I.; Kidd, Judith R.; Kidd, Kenneth K.

2008-01-01

Background The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations. As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region. Methodology/Principal Findings Here we report new data on 30 SNPs in the ADH7 and Class I ADH region in samples of 24 populations from China and Laos. These populations cover a wide geographic region and diverse ethnicities. Combined with our previously published East Asian data for these SNPs in 8 populations, we have typed populations from all of the 6 major linguistic phyla (Altaic including Korean-Japanese and inland Altaic, Sino-Tibetan, Hmong-Mien, Austro-Asiatic, Daic, and Austronesian). The ADH1B genotyping data are strongly related to ethnicity. Only some eastern ethnic phyla or subphyla (Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian) have a high frequency of ADH1B*47His. ADH1B haplotype data clustered the populations into linguistic subphyla, and divided the subphyla into eastern and western parts. In the Hmong-Mien and Altaic populations, the extended haplotype homozygosity (EHH) and relative EHH (REHH) tests for the ADH1B core were consistent with selection for the haplotype with derived SNP alleles. In the other ethnic phyla, the core showed only a weak signal of selection at best. Conclusions/Significance The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region

Ethnic related selection for an ADH Class I variant within East Asia.

PubMed

Li, Hui; Gu, Sheng; Cai, Xiaoyun; Speed, William C; Pakstis, Andrew J; Golub, Efim I; Kidd, Judith R; Kidd, Kenneth K

2008-04-02

The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations. As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region. Here we report new data on 30 SNPs in the ADH7 and Class I ADH region in samples of 24 populations from China and Laos. These populations cover a wide geographic region and diverse ethnicities. Combined with our previously published East Asian data for these SNPs in 8 populations, we have typed populations from all of the 6 major linguistic phyla (Altaic including Korean-Japanese and inland Altaic, Sino-Tibetan, Hmong-Mien, Austro-Asiatic, Daic, and Austronesian). The ADH1B genotyping data are strongly related to ethnicity. Only some eastern ethnic phyla or subphyla (Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian) have a high frequency of ADH1B*47His. ADH1B haplotype data clustered the populations into linguistic subphyla, and divided the subphyla into eastern and western parts. In the Hmong-Mien and Altaic populations, the extended haplotype homozygosity (EHH) and relative EHH (REHH) tests for the ADH1B core were consistent with selection for the haplotype with derived SNP alleles. In the other ethnic phyla, the core showed only a weak signal of selection at best. The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region. The obvious ethnicity-related distributions of ADH1B diversities

Genomic features of lobular breast carcinoma - TCGA

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

Increased N-myc downstream-regulated gene 1 expression is associated with breast atypia-to-carcinoma progression.

PubMed

Mao, Xiao-Yun; Fan, Chui-Feng; Wei, Jing; Liu, Cong; Zheng, Hua-Chuan; Yao, Fan; Jin, Feng

2011-12-01

N-myc downstream-regulated gene-1 (NDRG1) has been identified as a protein involved in the differentiation of epithelial cells. As a newly metastasis suppressor gene, whether it contributes to carcinogenesis of breast cancer is still unknown. This study aimed to clarify the possible role of NDRG1 for breast cancer carcinogenesis, and further to investigate its clinicopathological significance in invasive breast cancer. We examined the expression of NDRG1 in normal epithelium of breast (n = 35), usual ductal hyperplasia (n = 22), atypical ductal hyperplasia (n = 33), atypical lobular hyperplasia (n = 8), ductal carcinoma in situ (n = 16), lobular carcinoma in situ (n = 6), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 45) by immunohistochemistry and analyzed the correlation between NDRG expression and clinicopathological features of invasive breast cancer. Western blot analysis was carried out to investigate the expression of NDRG1 in 20 invasive ductal breast cancer and the paired non-tumor portion of the same case. NDRG1 expression in invasive breast cancer (70/95, 73.7%) was higher than that in noninvasive breast lesions (29/85, 34.1%; p < 0.05) which was higher than that in normal breast epithelium (5/35, 14.3%; p < 0.05). Statistical analysis revealed a significant correlation between NDRG1 expression with tumor stage in invasive breast cancer, and its expression in invasive ductal carcinoma is significantly higher than invasive lobular carcinoma (p < 0.05). It was not associated with age, menopausal status, tumor size, and lymph node metastasis. NDRG1 protein levels were significantly higher in invasive ductal breast cancer compared to the paired non-tumor portion of the same case by Western blot analysis (p < 0.05). Increased NDRG-1 expression is associated with breast atypia-to-carcinoma progression. NDRG1 expression might participate in the carcinogenesis and progression of invasive

Molecular phylogeny and evolution of alcohol dehydrogenase (Adh) genes in legumes

PubMed Central

Fukuda, Tatsuya; Yokoyama, Jun; Nakamura, Toru; Song, In-Ja; Ito, Takuro; Ochiai, Toshinori; Kanno, Akira; Kameya, Toshiaki; Maki, Masayuki

2005-01-01

Background Nuclear genes determine the vast range of phenotypes that are responsible for the adaptive abilities of organisms in nature. Nevertheless, the evolutionary processes that generate the structures and functions of nuclear genes are only now be coming understood. The aim of our study is to isolate the alcohol dehydrogenase (Adh) genes in two distantly related legumes, and use these sequences to examine the molecular evolutionary history of this nuclear gene. Results We isolated the expressed Adh genes from two species of legumes, Sophora flavescens Ait. and Wisteria floribunda DC., by a RT-PCR based approach and found a new Adh locus in addition to homologues of the Adh genes found previously in legumes. To examine the evolution of these genes, we compared the species and gene trees and found gene duplication of the Adh loci in the legumes occurred as an ancient event. Conclusion This is the first report revealing that some legume species have at least two Adh gene loci belonging to separate clades. Phylogenetic analyses suggest that these genes resulted from relatively ancient duplication events. PMID:15836788

Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

PubMed

Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

2016-11-01

There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Deep analysis of N-cadherin/ADH-1 interaction: a computational survey.

PubMed

Eslami, Mahboobeh; Nezafat, Navid; Khajeh, Sahar; Mostafavi-Pour, Zohreh; Bagheri Novir, Samaneh; Negahdaripour, Manica; Ghasemi, Younes; Razban, Vahid

2018-01-19

Due to the considerable role of N-cadherin in cancer metastasis, tumor growth, and progression, inhibition of this protein has been highly regarded in recent years. Although ADH-1 has been known as an appropriate inhibitor of N-cadherin in clinical trials, its chemical nature and binding mode with N-cadherin have not been precisely specified yet. Accordingly, in this study, quantum mechanics calculations were used to investigate the chemical nature of ADH-1. These calculations clarify the molecular properties of ADH-1 and determine its reactive sites. Based on the results, the oxygen atoms are suitable for electrophilic reactivity, while the hydrogen atoms that are connected to nitrogen atoms are the favorite sites for nucleophilic reactivity. The higher electronegativity of the oxygen atoms makes them the most reactive portions in this molecule. Molecular docking and molecular dynamics (MD) simulation have also been applied to specify the binding mode of ADH-1 with N-cadherin and determine the important residues of N-cadherin involving in the interaction with ADH-1. Moreover, the verified model by MD simulation has been studied to extract the free energy value and find driving forces. These calculations and molecular electrostatic potential map of ADH-1 indicated that hydrophobic and electrostatic interactions are almost equally involved in the implantation of ADH-1 in the N-cadherin binding site. The presented results not only enable a closer examination of N-cadherin in complex with ADH-1 molecule, but also are very beneficial in designing new inhibitors for N-cadherin and can help to save time and cost in this field.

Combined effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 alleles on alcoholism and chronic liver diseases.

PubMed

Tóth, Réka; Fiatal, Szilvia; Petrovski, Beáta; McKee, Martin; Adány, Róza

2011-01-01

The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45-64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/35Val allele increased the risk of excessive and problem drinking in homozygous form (OR=1.582, p=0.035, CI=1.034-2.421, OR=1.780, p=0.016, CI=1.113-2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR=0.368, p=0.019, CI=0.159-0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases.

Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.

PubMed

El-Naby, Noha Ed Hassab; Hassan Mohamed, Hameda; Mohamed Goda, Asmaa; El Sayed Mohamed, Ahmed

2017-06-01

A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature. We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center. This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls. Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003. Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

STRUCTURAL ESTIMATES OF TREATMENT EFFECTS ON OUTCOMES USING RETROSPECTIVE DATA: AN APPLICATION TO DUCTAL CARCINOMA IN SITU

PubMed Central

Gold, Heather Taffet; Sorbero, Melony E. S.; Griggs, Jennifer J.; Do, Huong T.; Dick, Andrew W.

2013-01-01

Analysis of observational cohort data is subject to bias from unobservable risk selection. We compared econometric models and treatment effectiveness estimates using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data for women diagnosed with ductal carcinoma in situ. Treatment effectiveness estimates for mastectomy and breast conserving surgery (BCS) with or without radiotherapy were compared using three different models: simultaneous-equations model, discrete-time survival model with unobserved heterogeneity (frailty), and proportional hazards model. Overall trends in disease-free survival (DFS), or time to first subsequent breast event, by treatment are similar regardless of the model, with mastectomy yielding the highest DFS over 8 years of follow-up, followed by BCS with radiotherapy, and then BCS alone. Absolute rates and direction of bias varied substantially by treatment strategy. DFS was underestimated by single-equation and frailty models compared to the simultaneous-equations model and RCT results for BCS with RT and overestimated for BCS alone. PMID:21602195

Understanding the premalignant potential of atypical hyperplasia through its natural history: A longitudinal cohort study

PubMed Central

Hartmann, Lynn C; Radisky, Derek C; Frost, Marlene H; Santen, Richard J; Vierkant, Robert A; Benetti, Lorelle L; Tarabishy, Yaman; Ghosh, Karthik; Visscher, Daniel W; Degnim, Amy C

2014-01-01

Atypical hyperplasia is a high risk premalignant lesion of the breast, but its biology is poorly understood. Many believe that atypical ductal hyperplasia (ADH) is a direct precursor for low-grade ductal breast cancer (BC) while atypical lobular hyperplasia (ALH) serves as a risk indicator. These assumptions underlie current clinical recommendations. We tested these assumptions by studying the characteristics of the breast cancers (BCs) that develop in women with ADH or ALH. Using the Mayo Benign Breast Disease Cohort, we identified all women with ADH or ALH from 1967–2001 and followed them for later BCs, characterizing side of BC vs side of atypia; time to BC; type, histology and grade of BC, looking for patterns consistent with precursors vs risk indicators. 698 women with atypical hyperplasia were followed a mean of 12.5 years; 143 developed BC. For both ADH and ALH, there is a 2:1 ratio of ipsilateral to contralateral BCs. The ipsilateral predominance is marked in the first five years, consistent with a precursor phenotype for both ADH and ALH. For both, there is a predominance of invasive ductal cancers with 69% of moderate or high-grade. 25% are node positive. Both ADH and ALH portend risk for DCIS and invasive BCs, predominantly ductal, with two thirds moderate or high-grade. The ipsilateral breast is at especially high risk for BC in the first five years after atypia, with risk remaining elevated in both breasts long-term. ADH and ALH behave similarly in terms of later BC endpoints. PMID:24480577

Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

PubMed

Yagmurdur, M C; Atac, F B; Tutar, N U; Verdi, H; Isiklar, I; Ozdemir, B H; Ozbek, N; Karakayali, H; Haberal, M

2008-01-01

The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

[Gene expression of H-FABP and FAS and its clinicopathological significance in breast infiltrating ductal carcinoma].

PubMed

Li, Hua; Lü, Qing; Xue, Hui; Dong, Li-hua; Yang, Hui-jun

2008-07-01

To detect the expression of Heart or Muscle Fatty acid binding protein (H-FABP) and fatty acid synthase (FAS) in human breast cancer cells. The expression levels of FAS and H-FABP in 81 ductal infiltrating carcinoma (DIC) were detected by RT-PCR, immunohistochemistry and Western blot analysis. The possible associations of the expression of the two proteins with major clinicopathological factors were analyzed. The expression of both H-FABP and FAS increased in DIC cells than in adjacent normal cells. But less H-FABP and FAS were found in grade III DIC than in grade I and grade II DIC (P < 0.05). There was a positive correlation between the expression of H-FABP and FAS. No correlations between the expressions of two genes with other clinicopathological factors were found. The higher expression of H-FABP in grade I and II DIC suggests an early increased response to the over-expression of FAS. The parallel increase of H-FABP and FAS expressions marks increased breast cancer risk.

Structure, Expression, Chromosomal Location and Product of the Gene Encoding Adh2 in Petunia

PubMed Central

Gregerson, R. G.; Cameron, L.; McLean, M.; Dennis, P.; Strommer, J.

1993-01-01

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes. PMID:8096485

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

PubMed

Yu, Xuejuan; Liu, Shangang; Chen, Zhaoqiu; Zhang, Pinliang; Zhang, Jianbo; Xu, Liang; Liu, Zengjun; Ren, Ruimei

2014-08-01

To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.

ROS1 expression in invasive ductal carcinoma of the breast related to proliferation activity.

PubMed

Eom, Minseob; Lkhagvadorj, Sayamaa; Oh, Sung Soo; Han, Airi; Park, Kwang Hwa

2013-05-01

ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.

ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity

PubMed Central

Eom, Minseob; Lkhagvadorj, Sayamaa; Oh, Sung Soo; Han, Airi

2013-01-01

Purpose ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. Materials and Methods Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). Results ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. Conclusion Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells. PMID:23549810

Transient Overexpression of adh8a Increases Allyl Alcohol Toxicity in Zebrafish Embryos

PubMed Central

Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P.; Scholz, Stefan

2014-01-01

Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma

PubMed Central

2009-01-01

Background Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA. Methods We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry. Results Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue. Conclusion Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined

[Studies on the role of high pressure baroreceptors in vasopressin (ADH) secretion. Effect of occlusion of common carotid and vertebral arteries on blood ADH level (author's transl)].

PubMed

Matsuzaki, M

1977-08-20

The role of baroreceptors in common carotid and vertebral arteries and arteries in the thoracic cavity in vasopressin secretion was investigated in this study. Effects of bilateral occlusion of common carotid and vertebral arteries on blood ADH level as well as mean arterial pressure were studied in common carotid arterial plexus-denervated dogs, cervically vagotomized dogs and intact dogs. Blood ADH titers were determined by bioassay technic before and 5 minutes after the occlusion of the arteries and were compared with the changes of mean arterial pressure (MAP). The following results were obtained. (1) Blood ADH titers and MAP were elevated by the occlusion of the common carotid arteries in both intact and vagotomized dogs, while they were not significantly affected in denervated dogs. Elevation of blood ADH titers was more pronounced in vagotomized dogs than in intact dogs. (2) Blood ADH titers and MAP were elevated by the occlusion of vertebral arteries in all groups of dogs. However, the elevation of blood ADH titers in denervated dogs was more pronounced than in intact dogs, but less than in vagotomized dogs. (3) The effects of the occlusion of common carotid arteries on blood ADH titers and MPA were more pronounced than those of the occlusion of vertebral arteries. These results may suggest that: a. baroreceptors involved in vasopressin secretion are present in vertebral arteries as well, and that b. the intrathoracic baroreceptors are dominant in controlling vasopressin secretion, while those in common carotid arteries are secondly and those in vertebral arteries thirdly dominant.

Metastatic Male Ductal Breast Cancer Mimicking Obstructing Primary Colon Cancer

PubMed Central

Koleilat, Issam; Syal, Anil; Hena, Muhammad

2010-01-01

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

[Practical problems in breast screening. Columnar cell lesions including flat epithelial atypia and lobular neoplasia].

PubMed

Nährig, J

2008-11-01

Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with increasing frequency in breast screening biopsies. CCLs are frequently associated with microcalcifications, whereas LN is an incidental finding in most cases. Flat epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed similar chromosomal alterations supporting the assumption that CCLs are neoplastic proliferations. The frequent association of FEA together with well differentiated invasive carcinomas provides further evidence of this concept. There is no internationally accepted classification of CCLs at present. CDH1-gene mutations are the cardinal feature of LN and invasive lobular carcinoma. In immunohistochemically CDH1-positive cases, alternative genetic alterations of the CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically and immunohistochemically hybrid lesions may represent this group of lobular lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in patients with previously diagnosed LN. It is currently an open question whether FEA and LN are members of a common family of intralobular proliferations, which are non-obligatory precursors of a low nuclear grade breast neoplasia family.

Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

PubMed

Kang, Gaeun; Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jin; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jong-Keun

2014-06-01

It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results

Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population.

PubMed

Méndez, Claudia; Rey, Mauricio

2015-12-30

Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism.

Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati.

PubMed

Yaacob, Norhayati; Mohamad Ali, Mohd Shukuri; Salleh, Abu Bakar; Abdul Rahman, Nor Aini

2016-01-01

Background. Not all yeast alcohol dehydrogenase 2 (ADH2) are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P)-binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2) and S. cerevisiae (SceADH2) in response to 2% (w/v) glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v) ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS) and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell-shaped ADH2

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

PubMed Central

Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.

PubMed

Chen, Qing-Xia; Li, Jun-Jing; Wang, Xiao-Xiao; Lin, Pei-Yang; Zhang, Jie; Song, Chuan-Gui; Shao, Zhi-Ming

2017-01-24

Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.

Ductal carcinoma in situ of the breast: can biomarkers improve current management?

PubMed

Bartlett, John M S; Nofech-Moses, Sharon; Rakovitch, Eileen

2014-01-01

Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women. We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area. DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.

The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.

PubMed

Surmacki, Jakub; Brozek-Pluska, Beata; Kordek, Radzislaw; Abramczyk, Halina

2015-04-07

Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.

SMAD4 is a potential prognostic marker in human breast carcinomas

PubMed Central

Liu, Nan-nan; Xi, Yue; Callaghan, Michael U.; Fribley, Andrew; Moore-Smith, Lakisha; Zimmerman, Jacquelyn W.; Pasche, Boris

2014-01-01

SMAD4 is a downstream mediator of transforming growth factor beta. While its tumor suppressor function has been investigated as a prognostic biomarker in several human malignancies, its role as a prognostic marker in breast carcinoma is still undefined. We investigated SMAD4 expression in breast carcinoma samples of different histologic grades to evaluate the association between SMAD4 and outcome in breast cancer. We also investigated the role of SMAD4 expression status in MDA-MB-468 breast cancer cells in responding to TGF-β stimulation. SMAD4 expression was assessed in 53 breast ductal carcinoma samples and in the surrounding normal tissue from 50 of the samples using immunohistochemistry, Western blot, and real-time PCR. TGF-β-SMAD and non-SMAD signaling was assessed by Western blot in MDA-MB-468 cells with and without SMAD4 restoration. SMAD4 expression was reduced in ductal breast carcinoma as compared to surrounding uninvolved ductal breast epithelia (p <0.05). SMAD4 expression levels decreased from Grade 1 to Grade 3 ductal breast carcinoma as assessed by immunohistochemistry (p <0.05). Results were recapitulated by tissue array. In addition, immunohistochemistry results were further confirmed at the protein and mRNA level. We then found that non-SMAD MEK/MAPK signaling was significantly different between SMAD4 expressing MDA-MB-468 cells and SMAD4-null MDA-MB-468 cells. This is the first study indicating that SMAD4 plays a key role in shifting MAPK signaling. Further, we have demonstrated that SMAD4 has a potential role in the development of breast carcinoma and SMAD4 was a potential prognostic marker of breast carcinoma. Our findings further support the role of SMAD4 in breast carcinoma development. In addition, we observed an inverse relationship between SMAD4 levels and breast carcinoma histological grade. Our finding indicated that SMAD4 expression level in breast cancer cells played a role in responding non-SMAD signaling but not the canonic SMAD

Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

NASA Technical Reports Server (NTRS)

Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

2003-01-01

Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

MRI versus breast-specific gamma imaging (BSGI) in newly diagnosed ductal cell carcinoma-in-situ: a prospective head-to-head trial.

PubMed

Keto, Jessica L; Kirstein, Laurie; Sanchez, Diana P; Fulop, Tamara; McPartland, Laura; Cohen, Ilona; Boolbol, Susan K

2012-01-01

Mammography remains the standard imaging technique for the diagnosis of ductal carcinoma-in-situ (DCIS). Functional breast imaging, including breast magnetic resonance imaging (MRI), has known limitations in evaluating DCIS. To date, there are limited data on the utility of breast-specific gamma imaging (BSGI) in DCIS. We sought to prospectively compare the sensitivity of BSGI to MRI in newly diagnosed DCIS patients. Patients with newly diagnosed DCIS from June 1, 2009, through May 31, 2010, underwent a protocol with both breast MRI and BSGI. Each imaging study was read by a separate dedicated breast radiologist. Patients were excluded if excisional biopsy was performed for diagnosis, if their MRI was performed at an outside facility, or if final pathology revealed invasive carcinoma. There were 18 patients enrolled onto the study that had both MRI and BSGI for newly diagnosed DCIS. The sensitivity for MRI was 94% and for BSGI was 89% (P > 0.5, NS). There was one index tumor not seen on either MRI or BSGI, and one index tumor seen on MRI but not visualized on BSGI. Although BSGI has previously been shown to be as sensitive as MRI for detecting known invasive breast carcinoma, this study shows that BSGI is equally as sensitive as MRI at detecting newly diagnosed DCIS. As a result of the limited number of patients enrolled onto the study, larger prospective studies need to be performed to determine the true sensitivity and specificity of BSGI.

Correlation between oestrogen receptor protein expression in infiltrating ductal carcinoma of the breast by immunohistochemistry and cytosol measurements.

PubMed

Looi, L M; Yap, S F; Cheah, P L

1997-11-01

Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.

Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study.

PubMed

Williams, Lindsay A; Nichols, Hazel B; Hoadley, Katherine A; Tse, Chiu Kit; Geradts, Joseph; Bell, Mary Elizabeth; Perou, Charles M; Love, Michael I; Olshan, Andrew F; Troester, Melissa A

2018-01-01

Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+). In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

PubMed

Zhang, Guohong; Mai, Ruiqin; Huang, Bo

2010-10-27

Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07). Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.

The management of ductal carcinoma in situ in North America and Europe. Results of a survey.

PubMed

Ceilley, Elizabeth; Jagsi, Reshma; Goldberg, Saveli; Kachnic, Lisa; Powell, Simon; Taghian, Alphonse

2004-11-01

The goal of the current study was to understand and document contemporary treatment approaches in the management of ductal carcinoma in situ (DCIS). An original questionnaire was designed to assess radiation oncologists' management of breast carcinoma, including 26 questions specifically addressing DCIS. A postal survey was conducted of members of the American and European Societies of Therapeutic Radiology and Oncology. The results of 702 responses from North America were compared with 435 responses from Europe, to determine treatment recommendations and variability by type of institution and geographic region. There were strong correlations between the grade of DCIS and/or the margin status and the use of radiotherapy (RT; P < 0.0001). For Grade 3 DCIS, RT was recommended regardless of the margin status. Opinions were split in the treatment of low-grade DCIS with 10-mm margins. North American respondents were more likely to recommend RT for low-grade DCIS than their European counterparts (P < 0.0001). Within the United States, there were significant regional variations in physician recommendations for tamoxifen (P < 0.001), but not in the tendency to recommend RT. North American academic physicians were less likely to recommend RT for favorable DCIS than nonacademic physicians (P < 0.01). There were marked differences in physician opinions regarding the management of DCIS, with significant international differences in patterns of care. The survey quantified and highlighted areas of agreement and controversy regarding the use of RT and tamoxifen in the management of DCIS. It provided support for large international trials to evaluate the optimal management of DCIS in the areas identified as most controversial.

Suppression of ADH during water immersion in normal man. [antidiuretic hormone

NASA Technical Reports Server (NTRS)

Epstein, M.; Pins, D. S.; Miller, M.

1975-01-01

A study was undertaken to ascertain whether diuresis induced by immersion is medicated by an inhibition of ADH. Immersion resulted in a progressive decrease in ADH excretion from 80.1 + or - 7 (SEM) to 37.3 + or - 6.3 microU/min (P less than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 + or - 6.3 microU/min to 176.6 + or - 72.6 microU/min during the recovery hour (P less than 0.05). Concomitant with these changes, urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 + or - 36 to 542 + or - 66 mosmol/kg H2O during the final hour of immersion (P less than 0.001). These findings are consistent with the earlier suggestion that suppression of ADH release contributes to enhanced free water clearance in hydrated subjects undergoing immersion.

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

PubMed

Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

2014-07-01

Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinicopathologic assessment of pancreatic ductal carcinoma located at the head of the pancreas, in relation to embryonic development.

PubMed

Okamura, Yukiyasu; Fujii, Tsutomu; Kanzaki, Akiyuki; Yamada, Suguru; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Nakao, Akimasa

2012-05-01

Pancreaticoduodenectomy is performed for pancreatic head cancer that originated from the dorsal or ventral primordium. Although the extent of lymph node (LN) dissection is the same irrespective of the origin, the lymphatic continuities may differ between the 2 primordia. Between March 2003 and September 2010, 152 patients underwent pancreaticoduodenectomy for pancreatic cancer. One hundred six patients were assigned into 2 groups according to tumor location on preoperative computed tomography, and their clinical and pathological features were retrospectively analyzed in view of the embryonic development of the pancreas. Sixty of 106 patients were classified with tumors that were derived from the dorsal pancreas (D group) and 46 from the ventral pancreas (V group). The frequency of LN involvement around the middle colic artery (LN 15) in the D group was higher than in the V group (P = 0.008). The rate of additional resection of the pancreas tended to be higher in the D group (P = 0.067). The present study showed the detailed pattern of spread of pancreatic ductal carcinoma to the LNs and provided important information for determining the optimal surgical strategy.

Ductal carcinoma in situ (DCIS) of the breast: the need for psychosocial research.

PubMed

Carrera, C; Payne, S

1999-01-01

Since the introduction of the National Health Service Breast Screening Programme (NHSBSP), the number of ductal carcinoma in situ (DCIS) cases has increased considerably. Despite its increased incidence, some NHS leaflets and reports do not mention it, and the general public seems largely unaware of its existence. There are numerous biological studies dealing with this condition, but its psychosocial aspects seem to have been neglected. We have only been able to locate two British studies (Farmer, A. 1996. Unpublished PhD thesis, University of Southampton; Webb, C. and Koch, T. 1997. J. Adv. Nurs., 25, 154-525) that address some of the psychosocial issues associated with DCIS. This paper starts by defining DCIS and explaining its usual presentation, natural history and epidemiology. The treatment options for DCIS are described, together with the great deal of confusion and lack of agreement that accompanies them. The psychological issues that women with screen-detected DCIS have to deal with are different from those affecting women diagnosed with symptomatic breast cancer, and a summary of these issues is given. Finally, some suggestions for future psychosocial research are provided. Because the UK as a whole was not covered by the NHSBSP until 1990 (Baum, M. 1995. Lancet, 346, 436; Gage and Fouquet, 1997), the main focus will be on papers published from that year onwards, although some key papers published before then will also be included. The papers reviewed here were found in MEDLINE, EMBASE and BIDS (ISI). Copyright 1999 John Wiley & Sons, Ltd.

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

PubMed

Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

2014-07-01

The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low ergosterol content in yeast adh1 mutant enhances chitin maldistribution and sensitivity to paraquat-induced oxidative stress.

PubMed

Marisco, G; Saito, S T; Ganda, I S; Brendel, M; Pungartnik, C

2011-05-01

Alcohol dehydrogenases catalyse the reversible oxidation of alcohols to aldehydes or ketones, with concomitant reduction of NAD(+) or NADP(+) . Adh1p is responsible for the reduction of acetaldehyde to ethanol, while Adh2p catalyses the reverse reaction, the oxidation of ethanol to acetaldehyde. Lack of Adh1p shifts the cellular redox balance towards excess NADH/NADPH and acetaldehyde, while absence of Adh2p does the opposite. Yeast mutant adh1Δ had a slow growth rate, whereas adh2Δ grew like the isogenic wild-type (WT) during prediauxic shift fermentative metabolism. After 48 h WT and mutants reached the same number of viable cells. When exponentially growing (LOG) cells were exposed to calcofluor white, only mutant adh1Δ displayed an irregular deposition of chitin. Quantitative analyses of both LOG and stationary-phase cells showed that adh1Δ mutant contained significantly less ergosterol than cells of WT and adh2Δ mutant, whereas the erg3Δ mutant contained extremely low ergosterol pools. Both adh1Δ and adh2Δ mutants showed higher-than-WT resistance to heat shock and to H(2) O(2) but had WT resistance when exposed to ultraviolet (UV) light and the DNA cross-linking agent diepoxyoctane, indicating normal DNA repair capacity. Mutant adh1Δ was specifically sensitive to acetaldehyde and to membrane peroxidizing paraquat. Our results link the pleiotropic phenotype of adh1Δ mutants to low pools of ergosterol and to reductive stress, and introduce the two new phenotypes, resistance to heat shock and to H(2) O(2) , for the adh2Δ mutant, most probably related to increased ROS production in mitochondria, which leads to the induction of oxidative stress protection. Copyright © 2011 John Wiley & Sons, Ltd.

A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast.

PubMed

Solin, Lawrence J; Gray, Robert; Baehner, Frederick L; Butler, Steven M; Hughes, Lorie L; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Page, David L; Sledge, George W; Davidson, Nancy E; Ingle, James N; Perez, Edith A; Wood, William C; Sparano, Joseph A; Badve, Sunil

2013-05-15

For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided. There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02). The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.

Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment

PubMed Central

Takagi, K; Ishida, T; Miki, Y; Hirakawa, H; Kakugawa, Y; Amano, G; Ebata, A; Mori, N; Nakamura, Y; Watanabe, M; Amari, M; Ohuchi, N; Sasano, H; Suzuki, T

2013-01-01

Background: Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment. Methods: Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis. Results: Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues. Conclusion: These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens. PMID:23756858

Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women.

PubMed

Looi, Lai-Meng; Cheah, Phaik-Leng; Ng, Min-Hwei; Yip, Cheng-Har; Mun, Kein-Seong; Rahman, Nazarina Abdul

2010-01-01

A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.

Protocol for Biomarker Ratio Imaging Microscopy with Specific Application to Ductal Carcinoma In situ of the Breast

PubMed Central

Clark, Andrea J.; Petty, Howard R.

2016-01-01

This protocol describes the methods and steps involved in performing biomarker ratio imaging microscopy (BRIM) using formalin fixed paraffin-embedded (FFPE) samples of human breast tissue. The technique is based on the acquisition of two fluorescence images of the same microscopic field using two biomarkers and immunohistochemical tools. The biomarkers are selected such that one biomarker correlates with breast cancer aggressiveness while the second biomarker anti-correlates with aggressiveness. When the former image is divided by the latter image, a computed ratio image is formed that reflects the aggressiveness of tumor cells while increasing contrast and eliminating path-length and other artifacts from the image. For example, the aggressiveness of epithelial cells may be assessed by computing ratio images of N-cadherin and E-cadherin images or CD44 and CD24 images, which specifically reflect the mesenchymal or stem cell nature of the constituent cells, respectively. This methodology is illustrated for tissue samples of ductal carcinoma in situ (DCIS) and invasive breast cancer. This tool should be useful in tissue studies of experimental cancer as well as the management of cancer patients. PMID:27857940

Effectiveness of Breast MRI and (18)F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma.

PubMed

Jung, Na Young; Kim, Sung Hoon; Kim, Sung Hun; Seo, Ye Young; Oh, Jin Kyoung; Choi, Hyun Su; You, Won Jong

2015-03-01

We evaluated the utility of magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC). The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and (18)F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups. Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on (18)F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of (18)F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of (18)F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with (18)F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or (18)F-FDG PET/CT for ILC versus IDC. The MRI and (18)F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although (18)F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of

Alcohol dehydrogenase AdhA plays a role in ethanol tolerance in model cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Vidal, Rebeca

2017-04-01

The protein AdhA from the cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis) has been previously reported to show alcohol dehydrogenase activity towards ethanol and both NAD and NADP. This protein is currently being used in genetically modified strains of Synechocystis capable of synthesizing ethanol showing the highest ethanol productivities. In the present work, mutant strains of Synechocystis lacking AdhA have been constructed and tested for tolerance to ethanol. The lack of AdhA in the wild-type strain reduces survival to externally added ethanol at lethal concentration of 4% (v/v). On the other hand, the lack of AdhA in an ethanologenic strain diminishes tolerance of cells to internally produced ethanol. It is also shown that light-activated heterotrophic growth (LAHG) of the wild-type strain is impaired in the mutant strain lacking AdhA (∆adhA strain). Photoautotrophic, mixotrophic, and photoheterotrophic growth are not affected in the mutant strain. Based on phenotypic characterization of ∆adhA mutants, the possible physiological function of AdhA in Synechocystis is discussed.

Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: Critical review.

PubMed

Toss, M; Miligy, I; Thompson, A M; Khout, H; Green, A R; Ellis, I O; Rakha, E A

2017-10-01

The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management protocols a more conservative approach has been suggested. Clinical trials have been introduced to evaluate the option of avoiding surgical intervention in a proportion of patients with DCIS defined as "low-risk" using certain clinicopathological criteria. These trials can potentially provide evidence-based models of active surveillance (with or without endocrine therapy) as a future management approach. Despite the undisputable fact of our need to address the obvious overtreatment of screen-detected DCIS, some important questions need to be considered regarding these trials including the eligibility criteria and definition of risk, the proportion of patient eligible for inclusion, and the length of time required for proper analysis of the trials' outcome in view of the long-term natural history of DCIS progression particularly the low-risk group. These factors can potentially affect the practicality and future impact of such trials. This review provides critical analysis of current DCIS management trials and highlights critical issues related to their practicality and the expected outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

An Examination of the Local Cellular Immune Response to Examples of Both Ductal Carcinoma In Situ (DCIS) of the Breast and DCIS With Microinvasion, With Emphasis on Tertiary Lymphoid Structures and Tumor Infiltrating Lymphoctytes.

PubMed

Kim, Ahrong; Heo, Sun-Hee; Kim, Young-Ae; Gong, Gyungyub; Jin Lee, Hee

2016-07-01

We tried to describe cellular immune response (tertiary lymphoid structures (TLSs), lymphoid aggregates, tumor infiltrating lymphocytes (TILs)) in neoplastic microenvironment of ductal carcinoma in situ (DCIS) with or without associated microinvasion. The histopathologic parameters of 177 DCIS and 27 DCIS with microinvasion were evaluated. We determined number of ducts involved by DCIS, and calculated percentage of these ducts surrounded by TLSs. TILs were quantitated in 27 microinvasive cases. Tumors having higher percentage of DCIS ducts associated with TLSs had higher incidence of microinvasion (P < .001). Percentage of DCIS ducts involved by TLSs was also higher in hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ and TNBC subtypes of DCIS than in HR+/HER2- and HR+/HER2+ subtypes (38.04 ± 25.8%, 32.6 ± 32.4%, 2.5 ± 7.3% and 17.4 ± 23.3%, respectively, P < .001). In DCIS without microinvasion, HR+/HER2- subtype predominated (P < .001). In microinvasive cases, HR-/HER2+ subtype was most common. TNBC was more common in microinvasive carcinoma than DCIS (P < .001). Among 27 microinvasive ductal carcinomas, increased TLS amount was associated with increased TILs (P = .013). TLS abundance around DCIS was associated with HER2+ and TNBC subtypes and microinvasion. Pathologists should be aware of microinvasion when diagnosing DCIS lesions with abundant TLSs. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast.

PubMed

Correa, C; McGale, P; Taylor, C; Wang, Y; Clarke, M; Davies, C; Peto, R; Bijker, N; Solin, L; Darby, S

2010-01-01

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.

Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

PubMed

Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

2015-08-01

The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same?

PubMed

Tang, Ping; Wang, Jianmin; Bourne, Patria

2008-04-01

There are 4 major molecular classifications in the literature that divide breast carcinoma into basal and nonbasal subtypes, with basal subtypes associated with poor prognosis. Basal subtype is defined as positive for cytokeratin (CK) 5/6, CK14, and/or CK17 in CK classification; negative for ER, PR, and HER2 in triple negative (TN) classification; negative for ER and negative or positive for HER2 in ER/HER2 classification; and positive for CK5/6, CK14, CK17, and/or EGFR; and negative for ER, PR, and HER2 in CK/TN classification. These classifications use similar terminology but different definitions; it is critical to understand the precise relationship between them. We compared these 4 classifications in 195 breast carcinomas and found that (1) the rates of basal subtypes varied from 5% to 36% for ductal carcinoma in situ and 14% to 40% for invasive ductal carcinoma. (2) The rates of basal subtypes varied from 19% to 76% for HG carcinoma and 1% to 7% for NHG carcinoma. (3) The rates of basal subtypes were strongly associated with tumor grades (P < .001) in all classifications and associated with tumor types (in situ versus invasive ductal carcinomas) in TN (P < .001) and CK/TN classifications (P = .035). (4) These classifications were related but not interchangeable (kappa ranges from 0.140 to 0.658 for HG carcinoma and from 0.098 to 0.654 for NHG carcinoma). In conclusion, although these classifications all divide breast carcinoma into basal and nonbasal subtypes, they are not interchangeable. More studies are needed to evaluate to their values in predicting prognosis and guiding individualized therapy.

Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

PubMed

Brück, N; Koskivuo, I; Boström, P; Saunavaara, J; Aaltonen, R; Parkkola, R

2018-03-01

Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p < 0.001). Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ of the Breast

PubMed Central

2013-01-01

Background For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. Methods The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided. Results There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02). Conclusions The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria. PMID:23641039

Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome

PubMed Central

Salujha, S. K.; Chaudhury, S.; Menon, P. K.; Srivastava, K.; Gupta, A.

2014-01-01

Background: The etiology of alcohol dependence is a complex interplay of biopsychosocial factors. The genes for alcohol-metabolizing enzymes: Alcohol dehydrogenase (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) exhibit functional polymorphisms. Vulnerability of alcohol dependence may also be in part due to heritable personality traits. Aim: To determine whether any association exists between polymorphisms of ADH2, ADH3 and ALDH2 and alcohol dependence syndrome in a group of Asian Indians. In addition, the personality of these patients was assessed to identify traits predisposing to alcoholism. Materials and Methods: In this study, 100 consecutive males with alcohol dependence syndrome attending the psychiatric outpatient department of a tertiary care service hospital and an equal number of matched healthy controls were included with their consent. Blood samples of all the study cases and controls were collected and genotyped for the ADH2, ADH3 and ALDH2 loci. Personality was evaluated using the neuroticism, extraversion, openness (NEO) personality inventory and sensation seeking scale. Results: Allele frequencies of ADH2*2 (0.50), ADH3*1 (0.67) and ALSH2*2 (0.09) were significantly low in the alcohol dependent subjects. Personality traits of NEO personality inventory and sensation seeking were significantly higher when compared to controls. Conclusions: The functional polymorphisms of genes coding for alcohol metabolizing enzymes and personality traits of NEO and sensation seeking may affect the propensity to develop dependence. PMID:25535445

WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.

PubMed

Domfeh, Akosua B; Carley, AnnaMarie L; Striebel, Joan M; Karabakhtsian, Rouzan G; Florea, Anca V; McManus, Kim; Beriwal, Sushil; Bhargava, Rohit

2008-10-01

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

PubMed Central

Reisle, Caralyn; Martin, Lee Ann; Alwelaie, Yazeed; Mungall, Karen L.; Ch'ng, Carolyn; Thomas, Ruth; Ng, Tony; Yip, Stephen; J. Lim, Howard; Sun, Sophie; Young, Sean S.; Karsan, Aly; Zhao, Yongjun; Mungall, Andrew J.; Moore, Richard A.; J. Renouf, Daniel; Gelmon, Karen; Ma, Yussanne P.; Hayes, Malcolm; Laskin, Janessa; Marra, Marco A.; Schrader, Kasmintan A.; Jones, Steven J. M.

2017-01-01

We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1. This is the first report of LMS genomic profiling in a patient with the germline CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that RAD51B translocation and HMGA2 overexpression may play an important role in LMS oncogenesis. PMID:28514723

The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

PubMed

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2009-01-01

The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

Selection of Treatment Among Latina and Non-Latina White Women with Ductal Carcinoma in Situ

PubMed Central

Nápoles, Anna M.; Hwang, E. Shelley; Bloom, Joan; Stewart, Susan; Nickleach, Dana; Karliner, Leah

2011-01-01

Abstract Background The growing rates of ductal carcinoma in situ (DCIS) and evidence that Latinas may underuse breast-conserving surgery (BCS) compared with white women highlight the need to better understand how treatment decisions are made in this understudied group. To help address this gap, this study compared surgery and radiation treatment decision making among white and Spanish-speaking and English-speaking Latina women with DCIS recruited from eight population-based cancer registries from 35 California counties. Methods Women aged ≥18 who self-identified as Latina or non-Latina white diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions and surveyed about their DCIS treatment decision making by telephone approximately 24 months after diagnosis. Survey data were merged with CCR hospital-based records to obtain tumor and treatment data. Results Mean age was 57 years. Multivariate analysis indicated no differences by ethnicity or language in the receipt of mastectomy vs. BCS after controlling demographic, health, and personal preferences. English-speaking Latinas were more likely to receive radiation than their Spanish-speaking or white counterparts, controlling for demographic and other factors. Among women receiving BCS, physician recommendation was the strongest predictor of receipt of radiation. Conclusions Ethnic disparities in surgical treatment choices after breast cancer diagnosis were not seen in this cohort of women diagnosed with DCIS. Physicians play an essential role in patients' treatment choices for DCIS, particularly for adjuvant radiation. PMID:21128819

Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma.

PubMed Central

Gamallo, C.; Palacios, J.; Suarez, A.; Pizarro, A.; Navarro, P.; Quintanilla, M.; Cano, A.

1993-01-01

Recently, a correlation has been suggested between a loss of E-cadherin (E-CD) and increased invasiveness of neoplastic cells. In this study, E-CD expression in breast cancer was investigated using an affinity-purified antibody (ECCD-2) in an immunoenzymatic (avidin-biotin-alkaline phosphatase) test. Intensity and extension of E-CD immunoreactivity were evaluated in 61 breast carcinomas and correlated with their histological type and grade, nodal involvement, and hormonal receptor status. Histological types were infiltrating ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7). All infiltrating ductal carcinomas of no special type except two grade 3 carcinomas showed positive immunoreactivity that was variable among different cases. Grade 1 breast carcinomas (n = 10) showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19) carcinomas. E-CD immunoreactivity correlated positively with the degree of tubular formation and inversely with the mitoses number. None of the infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they showed only weak immunostains in areas of atypical lobular hyperplasia and lobular carcinoma in situ. These results indicate that E-CD expression correlates with histological type and grade in breast carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:7682767

Radial scars diagnosed on breast core biopsy: Frequency of atypia and carcinoma on excision and implications for management.

PubMed

Donaldson, Alana R; Sieck, Leah; Booth, Christine N; Calhoun, Benjamin C

2016-12-01

The risk of finding carcinoma in excisions following a core needle biopsy diagnosis of radial scar is not well defined and clinical management is variable. The aim of this study is to determine the frequency of high-risk lesions, ductal carcinoma in situ, and invasive carcinoma in excisions following a core biopsy diagnosis of radial scar. Dedicated breast pathologists and radiologists correlated the histologic and radiologic findings and categorized radial scars as the target lesion or an incidental finding. High-risk lesions were defined as atypical hyperplasia or classical lobular carcinoma in situ. Of the 79 radial scars identified over a 14-year period, 22 were associated with atypia or carcinoma in the core biopsy. Thirty-seven (37) of the 57 benign radial scars underwent excision with benign findings in 30 (81%), high-risk lesions in six (16%), and flat epithelial atypia in one (3%). There were no upgrades to carcinoma. One patient with a benign radial scar developed a 3-mm focus of intermediate-grade estrogen receptor-positive ductal carcinoma in situ in the same quadrant of the ipsilateral breast 72 months after excision. One patient with an incidental un-excised benign radial scar was diagnosed with ductal carcinoma in situ at a separate site of suspicious calcifications. In this series, none of the benign radial scars was upgraded to carcinoma. Radial scar was the targeted lesion in all cases with high-risk lesions on excision. Surgical excision may not be mandatory for patients with benign incidental radial scars on core biopsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

PubMed

Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

2017-08-15

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017

Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model.

PubMed

Linsk, Ali; Mehta, Tejas S; Dialani, Vandana; Brook, Alexander; Chadashvili, Tamuna; Houlihan, Mary Jane; Sharma, Ranjna

2018-03-01

Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are commonly seen on breast core needle biopsy (CNB). Many institutions recommend excision of these lesions to exclude malignancy. A retrospective chart review was performed on patients who had ADH, ALH, or LCIS on breast CNB from 1/1/08 to 12/31/10 who subsequently had surgical excision of the biopsy site. Study objectives included determining upgrade to malignancy at surgical excision, identification of predictors of upgrade, and validation of a recently published predictive model. Clinical and demographic factors, pathology, characteristics of the biopsy procedure and visible residual lesion were recorded. T test and chi-squared test were used to identify predictors. Classification tree was used to predict upgrade. 151 patients had mean age of 53 years. The mean maximum lesion size on imaging was 11 mm. The primary atypia was ADH in 63.6%, ALH in 27.8%, and LCIS in 8.6%. 16.6% of patients had upgrade to malignancy, with 72% DCIS and 28% invasive carcinoma. Risk factors for upgrade included maximum lesion size (P = .002) and radiographic presence of residual lesion (P = .001). A predictive model based on these factors had sensitivity 78%, specificity 80% and AUC = 0.88. Validating a published nomogram with our data produced accuracy figures (AUC = 0.65) within published CI of 0.63-0.82. In CNB specimens containing ADH, ALH, or LCIS, initial lesion size and presence of residual lesion are predictors of upgrade to malignancy. A validated model may be helpful in developing patient management strategies. © 2017 Wiley Periodicals, Inc.

Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

PubMed

Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

2008-09-01

Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

PubMed

Withrow, Diana R; Morton, Lindsay M; Curtis, Rochelle E; Schonfeld, Sara J; Berrington de González, Amy

2017-11-01

Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis. Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.

[Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations].

PubMed

2005-11-01

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.

Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent surgical excision.

PubMed

Bianchi, Simonetta; Bendinelli, Benedetta; Castellano, Isabella; Piubello, Quirino; Renne, Giuseppe; Cattani, Maria Grazia; Di Stefano, Domenica; Carrillo, Giovanna; Laurino, Licia; Bersiga, Alessandra; Giardina, Carmela; Dante, Stefania; Di Loreto, Carla; Quero, Carmela; Antonacci, Concetta Maria; Palli, Domenico

2012-10-01

Flat epithelial atypia (FEA) may represent the earliest precursor of low-grade breast cancer and often coexists with more advanced atypical proliferative breast lesions such as atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN). The present study aims to investigate the association between morphological parameters of FEA and presence of malignancy at surgical excision (SE) and the clinical significance of the association of FEA with ADH and/or LIN. This study included 589 cases of stereotactic 11-gauge vacuum-assisted needle core biopsy (VANCB), reporting a diagnosis of FEA, ADH or LIN with subsequent SE from 14 pathology departments in Italy. Available slides were reviewed, with 114 (19.4 %) showing a malignant outcome at SE. Among the 190 cases of pure FEA, no statistically significant association emerged between clinical-pathological parameters of FEA and risk of malignancy. Logistic regression analyses showed an increased risk of malignancy according to the extension of ADH among the 275 cases of FEA associated with ADH (p = 0.004) and among the 34 cases of FEA associated with ADH and LIN (p = 0.02). In the whole series, a statistically significant increased malignancy risk emerged according to mammographic R1-R3/R4-R5 categories (OR = 1.56; p = 0.04), extension (OR = 1.24; p = 0.04) and grade (OR = 1.94; p = 0.004) of cytological atypia of FEA. The presence of ADH was associated with an increased malignancy risk (OR = 2.85; p < 0.0001). Our data confirm the frequent association of FEA with ADH and/or LIN. A diagnosis of pure FEA on VANCB carries a 9.5 % risk of concurrent malignancy and thus warrants follow-up excision because none of the clinical-pathological parameters predicts which cases will present carcinoma on SE.

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.

1990-01-01

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

PubMed Central

2010-01-01

Background Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Results Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. Conclusion The remarkable similarity of feline mammary IELs to those of humans

International variation in management of screen-detected ductal carcinoma in situ of the breast

PubMed Central

Ponti, Antonio; Lynge, Elsebeth; James, Ted; Májek, Ondřej; von Euler-Chelpin, My; Anttila, Ahti; Fitzpatrick, Patricia; Mano, Maria Piera; Kawai, Masaaki; Scharpantgen, Astrid; Fracheboud, Jacques; Hofvind, Solveig; Vidal, Carmen; Ascunce, Nieves; Salas, Dolores; Bulliard, Jean-Luc; Segnan, Nereo; Kerlikowske, Karla; Taplin, Stephen

2014-01-01

Background Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. Methods We sought screen-detected DCIS data from the ICSN countries identified during 2004–2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. Results Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50–69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67–90% of DCIS received breast conservation surgery (BCS), and in 41–100% of the cases this was followed by radiotherapy; 6.4–59% received sentinel lymph node biopsy (SLNB) only and 0.8–49% axillary dissection (ALND) with 0.6% (range by programmes 0–8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. Conclusions Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction. PMID:25149183

Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung

2013-11-01

Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatmentmore » in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.« less

Quality of life of Latina and Euro-American women with ductal carcinoma in situ.

PubMed

Bloom, Joan R; Stewart, Susan L; Napoles, Anna M; Hwang, E Shelly; Livaudais, Jennifer C; Karliner, Leah; Kaplan, Celia P

2013-05-01

Risk factors for psychosocial distress following a breast cancer diagnosis include younger age, history of depression, inadequate social support, and serious comorbid conditions. Although these quality of life (QOL) concerns have been studied in women with ductal carcinoma in situ (DCIS), Latina women have been understudied. Data were from a cross-sectional telephone survey of Latina and Euro-American women with DCIS recruited through a population-based cancer registry. The sample included 396 Euro-American women and 349 Latina women; 156 were interviewed in English and 193 in Spanish, with a median of 2 years after diagnosis. Regression models were created for measures in each of the following four QOL domains: physical, psychological, social, and spiritual. Younger age, no partner, and lower income were related to lower QOL in various domains. Physical comorbidities were associated with lower physical, psychological, and social QOL; lingering effects of surgery and prior depression were associated with lower QOL in all domains. English-speaking and Spanish-speaking Latinas (SSLs) reported higher spiritual QOL, and SSLs reported lower social QOL than Euro-American women. Despite having lower mortality, women with DCIS are treated with surgery and radiation therapy as if they have invasive cancer, and the aftereffects of treatment can impact their QOL. SSLs are at risk for lower QOL partly because of poverty. However, Latinas' greater spiritual QOL may mitigate some of the psychological and social effects of treatment. It is important to incorporate these findings into treatment decision making (choice of surgical treatment) and survivorship care (monitoring women with a history of depression or physical comorbidity). Copyright © 2012 John Wiley & Sons, Ltd.

Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

PubMed

Shi, Bibo; Grimm, Lars J; Mazurowski, Maciej A; Baker, Jay A; Marks, Jeffrey R; King, Lorraine M; Maley, Carlo C; Hwang, E Shelley; Lo, Joseph Y

2018-03-01

The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma.

PubMed

Thibodeau, My Linh; Reisle, Caralyn; Zhao, Eric; Martin, Lee Ann; Alwelaie, Yazeed; Mungall, Karen L; Ch'ng, Carolyn; Thomas, Ruth; Ng, Tony; Yip, Stephen; J Lim, Howard; Sun, Sophie; Young, Sean S; Karsan, Aly; Zhao, Yongjun; Mungall, Andrew J; Moore, Richard A; J Renouf, Daniel; Gelmon, Karen; Ma, Yussanne P; Hayes, Malcolm; Laskin, Janessa; Marra, Marco A; Schrader, Kasmintan A; Jones, Steven J M

2017-09-01

We describe a woman with the known pathogenic germline variant CHEK2 :c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2 :c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway ( CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1 This is the first report of LMS genomic profiling in a patient with the germline CHEK2 :c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that RAD51B translocation and HMGA2 overexpression may play an important role in LMS oncogenesis. © 2017 Thibodeau et al.; Published by Cold Spring Harbor Laboratory Press.

Knowledge, satisfaction with information, decisional conflict and psychological morbidity amongst women diagnosed with ductal carcinoma in situ (DCIS).

PubMed

De Morgan, Simone; Redman, Sally; D'Este, Catherine; Rogers, Kris

2011-07-01

To assess knowledge, satisfaction with information, decisional conflict and psychological morbidity amongst women diagnosed with ductal carcinoma in situ (DCIS) and to explore the factors associated with less knowledge and greater confusion about DCIS. A cross-sectional survey of women diagnosed with DCIS in Australia (N=144). This study found misunderstanding and confusion amongst women diagnosed with DCIS and a desire for more information about their breast disease. Approximately half of participants worried about their breast disease metastasizing; approximately half expressed high decisional conflict; 12% were anxious and 2% were depressed. Logistic regression analysis demonstrated that worry about dying from the breast disease was significantly associated with not knowing that DCIS could not metastasize (OR 3.9; 95% CI 1.03-14.25); and confusion about whether DCIS could metastasize was significantly associated with dissatisfaction with information (OR 12.5; 95% CI 3.8-40.2). Good communication about how DCIS differs from invasive breast cancer is essential to alleviating the confusion and worry amongst women with DCIS. Recommendations about how best to communicate a diagnosis of DCIS, including the uncertainties, are needed to guide health professionals to promote better understanding about DCIS and increase the well-being of women with DCIS. Copyright © 2010. Published by Elsevier Ireland Ltd.

Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features

NASA Astrophysics Data System (ADS)

Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2017-03-01

Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 +/- 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.

Majority of flat epithelial atypia diagnosed on biopsy do not require surgical excision.

PubMed

Chan, Patrick Mun Yew; Chotai, Niketa; Lai, Eileen Shujuan; Sin, Pei Yi; Chen, Juliana; Lu, Sarah Qinghui; Goh, Mui Heng; Chong, Bee Kiang; Ho, Bernard Chi Shern; Tan, Ern Yu

2018-02-01

Borderline risk lesions such as flat epithelial atypia (FEA) are increasingly being diagnosed on biopsy. The need for surgery is being debated. In this study, we determined the frequency of histological upgrade following a diagnosis of FEA on biopsy and evaluated potential predictive factors. Retrospective review was done of 194 women who underwent biopsy of indeterminate lesions (total 195 lesions) that were diagnosed as FEA. The review covered a 10-year period. Cases where malignancy was also present together with FEA within the same biopsy cores were excluded. Lesions diagnosed as FEA on biopsy were mostly asymptomatic and presented as microcalcifications on mammogram. Flat epithelial atypia was the only abnormality detected in one-third of cases, was associated with a benign or another borderline lesion in another third and was associated with atypical ductal hyperplasia (ADH) in another third. Six patients (3.1%) were later found to have ductal carcinoma-in-situ (DCIS) at surgery. The presence of ADH in the biopsy was the only predictor of histological upgrade to malignancy (P = 0.04, OR 11.24, 95% CI 1.10 - 115.10), and was present in 5 of the 6 patients. Surgery was advised in the last patient because of radiology-pathology discordance. Thirty-six lesions (18.5%) were not excised and no interval progression or malignancy was found on follow up. Histological upgrade to malignancy was uncommon in lesions found on biopsy to be FEA. Non-operative management of biopsy-proven FEA can be considered in the absence of ADH and radiology-pathology discordance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas, incidental or non-incidental?

PubMed

Zaleski, Michael; Chen, Yun An; Chetlen, Alison L; Mack, Julie; Xu, Liyan; Dodge, Daleela G; Karamchandani, Dipti M

2018-05-11

The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non-incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8-Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision. Copyright © 2018 Elsevier Inc. All rights reserved.

Structure of Escherichia coli AdhP (ethanol-inducible dehydrogenase) with bound NAD.

PubMed

Thomas, Leonard M; Harper, Angelica R; Miner, Whitney A; Ajufo, Helen O; Branscum, Katie M; Kao, Lydia; Sims, Paul A

2013-07-01

The crystal structure of AdhP, a recombinantly expressed alcohol dehydrogenase from Escherichia coli K-12 (substrain MG1655), was determined to 2.01 Å resolution. The structure, which was solved using molecular replacement, also included the structural and catalytic zinc ions and the cofactor nicotinamide adenine dinucleotide (NAD). The crystals belonged to space group P21, with unit-cell parameters a = 68.18, b = 118.92, c = 97.87 Å, β = 106.41°. The final R factor and Rfree were 0.138 and 0.184, respectively. The structure of the active site of AdhP suggested a number of residues that may participate in a proton relay, and the overall structure of AdhP, including the coordination to structural and active-site zinc ions, is similar to those of other tetrameric alcohol dehydrogenase enzymes.

adhA in Aspergillus parasiticus Is Involved in Conversion of 5′-Hydroxyaverantin to Averufin

PubMed Central

Chang, Perng-Kuang; Yu, Jiujiang; Ehrlich, Kenneth C.; Boue, Stephen M.; Montalbano, Beverly G.; Bhatnagar, Deepak; Cleveland, Thomas E.

2000-01-01

Two routes for the conversion of 5′-hydroxyaverantin (HAVN) to averufin (AVF) in the synthesis of aflatoxin have been proposed. One involves the dehydration of HAVN to the lactone averufanin (AVNN), which is then oxidized to AVF. Another requires dehydrogenation of HAVN to 5′-ketoaverantin, the open-chain form of AVF, which then cyclizes spontaneously to AVF. We isolated a gene, adhA, from the aflatoxin gene cluster of Aspergillus parasiticus SU-1. The deduced ADHA amino acid sequence contained two conserved motifs found in short-chain alcohol dehydrogenases—a glycine-rich loop (GXXXGXG) that is necessary for interaction with NAD+-NADP+, and the motif YXXXK, which is found at the active site. A. parasiticus SU-1, which produces aflatoxins, has two copies of adhA (adhA1), whereas A. parasiticus SRRC 2043, a strain that accumulates O-methylsterigmatocystin (OMST), has only one copy. Disruption of adhA in SRRC 2043 resulted in a strain that accumulates predominantly HAVN. This result suggests that ADHA is involved in the dehydrogenation of HAVN to AVF. Those adhA disruptants that still made small amounts of OMST also accumulated other metabolites, including AVNN, after prolonged culture. PMID:11055914

Health behavior change following a diagnosis of ductal carcinoma in situ: An opportunity to improve health outcomes.

PubMed

Berkman, Amy M; Trentham-Dietz, Amy; Dittus, Kim; Hart, Vicki; Vatovec, Christine M; King, John G; James, Ted A; Lakoski, Susan G; Sprague, Brian L

2015-11-01

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that comprises approximately 20% of new breast cancer diagnoses. DCIS is predominantly detected by screening mammography prior to the development of any clinical symptoms. Prognosis following a DCIS diagnosis is excellent, due to both the availability of effective treatments and the frequently benign nature of the disease. However, a DCIS diagnosis and its treatment have psychological and physical impacts that often lead to adverse changes in health-related behaviors, including changes in physical activity, body weight, alcohol intake, and smoking, which may represent a greater threat to the woman's overall health than the DCIS itself. Depending on age at diagnosis, women diagnosed with DCIS are 3-13 times more likely to die from non-breast cancer related causes, such as cardiovascular disease, than from breast cancer. Thus, the maintenance and improvement of healthy behaviors that influence a variety of outcomes after diagnosis may warrant increased attention during DCIS management. This may also represent an important opportunity to promote the adoption of healthy behaviors, given that DCIS carries the psychological impact of a cancer diagnosis but also a favorable prognosis. Particular focus is needed to address these issues in vulnerable patient subgroups with pre-existing higher rates of unhealthy behaviors and demonstrated health disparities. Copyright © 2015 Elsevier Inc. All rights reserved.

A Patient-centered Approach to Evaluate the Information Needs of Women With Ductal Carcinoma In Situ.

PubMed

Lo, Andrea C; Olson, Robert; Feldman-Stewart, Deb; Truong, Pauline T; Aquino-Parsons, Christina; Bottorff, Joan L; Carolan, Hannah

2017-12-01

To evaluate the information needs of ductal carcinoma in situ (DCIS) patients. Four focus groups involving 24 previously treated DCIS patients were conducted to develop a comprehensive list of questions they felt were important to have answered at the time of diagnosis. Using a survey, a separate group of patients treated for DCIS then rated the importance of having each of these questions addressed before treatment decision making. Response options were "essential," "desired," "not important," "no opinion," and "avoid." For each essential/desired question, respondents specified how addressing it would help them: "understand," "decide," "plan," "not sure," or "other." Focus group participants generated 117 questions used in the survey. Fifty-seven patients completed the survey (55% response rate). Respondents rated a median of 66 questions as essential. The most commonly cited reason for rating a question essential was to "understand," followed by to "decide." The top questions women deemed essential to help them understand were disease specific, whereas the top questions deemed essential to help women decide were predominantly treatment specific, pertaining to available options, recurrence and survival outcomes, and timelines to decide and start treatment. DCIS patients want a large number of questions answered, mostly for understanding, and also for deciding and planning. A core set of questions that most patients consider essential for decision making has been formulated and may be used in the clinical setting and in research to develop educational resources and decision-making tools specific to DCIS.

Screening of Two ADH4 Variations in a Swedish Cluster Headache Case–Control Material

PubMed Central

Fourier, Carmen; Ran, Caroline; Steinberg, Anna; Sjöstrand, Christina; Waldenlind, Elisabet

2016-01-01

Background Cluster headache (CH) is a severe neurovascular disorder and an increasing amount of evidence points to a genetic contribution to this disease. When CH was first described, it was observed that alcohol may precipitate an attack during the active phase of the disease. The alcohol dehydrogenase 4 (ADH4) gene encodes an enzyme which contributes to the metabolization of alcohol and is, therefore, an interesting candidate gene for CH. Two Italian groups have reported association of the single nucleotide polymorphism (SNP) rs1126671 located in the ADH4 gene with an increased risk of CH in Italy. In addition, one of the groups found an association between the ADH4 SNP rs1800759 and CH. Objective To perform a replication study on the ADH4 SNPs rs1126671 and rs1800759 in a large homogeneous Swedish case–control cohort in order to further investigate the possible contribution of ADH4 to CH. Methods A total of 390 unrelated patients diagnosed with CH and 389 controls representing a general Swedish population were recruited to the study. DNA samples from patients and controls were genotyped for the two ADH4 SNPs rs1126671 and rs1800759 using quantitative real‐time polymerase chain reaction. Statistical analyses of genotype, allele and haplotype frequencies for the two SNPs were performed and compared between patients and controls. Results For rs1126671, the minor allele frequency (A allele) was 32.8% (n = 254) in controls compared with 31.9% (n = 249) in CH patients. The minor allele frequency (A allele) of rs1800759 was 42.3% (n = 324) in controls and 41.9% (n = 327) in CH patients. Statistical analysis showed no significant differences in allele as well as in genotype or haplotype frequencies between the patient and control group for either SNP. This was also seen after stratifying the patient group for experiencing alcohol as a trigger factor. Conclusions The data did not support an association of the ADH4 SNPs rs1126671 and rs1800759 with CH

High-grade adenocarcinoma, (ductal type) arising in unilateral Warthin tumor of the parotid gland.

PubMed

Deodhar, Kedar K; Shah, Milap; Chaturvedi, Pankaj

2011-01-01

Warthin tumor is a well-recognized benign salivary gland neoplasm consisting of an epithelial as well as a lymphoid component. Malignant transformation in Warthin tumor is rare and its reported incidence is up to 1%. The more common types of carcinomas described in Warthin tumor are the squamous and mucoepidermoid types, with high-grade adenocarcinoma being extremely rare. A high-grade adenocarcinoma (ductal type) arising in the Warthin tumor in a 72-year-old man is presented for its rarity and diagnostic difficulties.

The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

PubMed Central

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian

2009-01-01

Background The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. Methods and Results we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. Conclusion these data support the activation of neurotensinergic deleterious pathways in breast cancer progression. PMID:19156213

The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.

PubMed

Gurzu, Simona; Banias, Laura; Bara, Tivadar; Feher, I; Bara, Tivadar; Jung, Ioan

2018-01-01

Metastases to the stomach are extremely rare and the metastatic pathway is not well understood. To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells. The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents. In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, β-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma. In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/β-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma.

PubMed

Fan, Chuifeng; Zhao, Yang; Mao, Xiaoyun; Miao, Yuan; Lin, Xuyong; Jiang, Guiyang; Zhang, Xiupeng; Han, Qiang; Luan, Lan; Wang, Enhua

2014-11-01

Armadillo repeat-containing protein 8 (Armc8) is a key factor to regulate cell membrane adhesion complex through promoting α-catenin degradation. However, its expression and function in human malignant tumors are largely unknown. Here, we present our study investigating Armc8 expression in tumor and non-tumor breast tissues including 45 normal epithelia, 53 lesions of hyperplasia with or without dysplasia, 22 benign tumors, and 92 carcinomas including 28 carcinomas in situ and 64 infiltrating carcinomas using immunohistochemistry (IHC) and Western blotting study. Armc8 expression was detected mainly in the cytoplasm with occasional membrane immunostaining. The positive rate of Armc8 expression in normal breast epithelia (8.9%, four out of 45) was very low. No significant difference was found between Armc8 expression in usual ductal hyperplasia (UDH) (11.1%, two out of 18), benign breast tumors including intraductal papilloma (10.0%, one out of 10) and fibroadenoma (8.3%, one out of 12), and normal breast epithelia (p>0.05). Elevated expression of Armc8 was found in breast epithelia with dysplasia (24.0%, six out of 25) compared to that in normal breast epithelia, UDH, and benign breast tumors (p<0.05). Armc8 expression in breast carcinoma including breast carcinoma in situ (10/28, 35.7%), infiltrating ductal carcinoma (60.7%, 34/56), and infiltrating lobular carcinoma (50.0%, 4/8) was higher than that in normal breast epithelia, UDH, benign breast tumors, and breast epithelia with dysplasia (p<0.05). The highest expression of Armc8 was found in infiltrating breast carcinoma (59.4%, 38/64) compared to all the other breast tissues. Higher Armc8 expression was found to be linked to lymph node metastasis and advanced tumor-node-metastasis (TNM) stages (III+IV) in infiltrating breast carcinoma (p<0.05). We further confirmed Armc8 expression in breast epithelial cell line MCF10A and breast carcinoma cell lines including MCF-7, MDA-MB-231, and ZR751 using Western

Cloning of the Arabidopsis and Rice Formaldehyde Dehydrogenase Genes: Implications for the Origin of Plant Adh Enzymes

PubMed Central

Dolferus, R.; Osterman, J. C.; Peacock, W. J.; Dennis, E. S.

1997-01-01

This article reports the cloning of the genes encoding the Arabidopsis and rice class III ADH enzymes, members of the alcohol dehydrogenase or medium chain reductase/dehydrogenase superfamily of proteins with glutathione-dependent formaldehyde dehydrogenase activity (GSH-FDH). Both genes contain eight introns in exactly the same positions, and these positions are conserved in plant ethanol-active Adh genes (class P). These data provide further evidence that plant class P genes have evolved from class III genes by gene duplication and acquisition of new substrate specificities. The position of introns and similarities in the nucleic acid and amino acid sequences of the different classes of ADH enzymes in plants and humans suggest that plant and animal class III enzymes diverged before they duplicated to give rise to plant and animal ethanol-active ADH enzymes. Plant class P ADH enzymes have gained substrate specificities and evolved promoters with different expression properties, in keeping with their metabolic function as part of the alcohol fermentation pathway. PMID:9215914

Association between ADH1C and ALDH2 polymorphisms and alcoholism in a Turkish sample.

PubMed

Ayhan, Yavuz; Gürel, Şeref Can; Karaca, Özgür; Zoto, Teuta; Hayran, Mutlu; Babaoğlu, Melih; Yaşar, Ümit; Bozkurt, Atilla; Dilbaz, Nesrin; Uluğ, Berna Diclenur; Demir, Başaran

2015-04-01

Polymorphisms in the genes encoding alcohol metabolizing enzymes are associated with alcohol dependence. To evaluate the association between the alcohol dehydrogenase 1C (ADH1C) Ile350Val and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphisms and alcohol dependence in a Turkish sample. 235 individuals (115 alcohol-dependent patients and 120 controls) were genotyped for ADH1C and ALDH2 with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Association between the polymorphisms and family history, daily and maximum amount of alcohol consumed was investigated. The associations between alcohol dependence, severity of consumption and family history and the polymorphisms were analyzed by chi-square or Fisher's exact test where necessary. Relationship between genotypes and dependence related features was evaluated using analysis of variance (ANOVA). The -350Val allele for ADH1C (ADH1C*2) was increased in alcohol-dependent patients (P = 0.05). In individuals with a positive family history, the genotype distribution differed significantly (P = 0.031) and more patients carried the Val allele compared with controls (P = 0.025). Genotyping of 162 participants did not reveal the -504Lys allele in ALDH2. These findings suggest that ADH1C*2 is associated with alcohol dependence in the Turkish population displaying a dominant inheritance model. ADH1C*2 allele may contribute to the variance in heritability of alcohol dependence. The ALDH2 -504Lys/Lys or Glu/Lys genotypes were not present in alcohol-dependent patients, similar to that seen in European populations and in contrast to the findings in the Asian populations.

Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

PubMed

Leonardi, Maria Cristina; Maisonneuve, Patrick; Mastropasqua, Mauro Giuseppe; Cattani, Federica; Fanetti, Giuseppe; Morra, Anna; Lazzari, Roberta; Bazzani, Federica; Caputo, Mariangela; Rotmensz, Nicole; Gerardi, Marianna Alessandra; Ricotti, Rosalinda; Enrica Galimberti, Viviana; Veronesi, Paolo; Dicuonzo, Samantha; Viale, Giuseppe; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto

2017-09-01

To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering substrate promiscuity in halophilic alcohol dehydrogenase (HvADH2) by in silico design.

PubMed

Cassidy, Jennifer; Bruen, Larah; Rosini, Elena; Molla, Gianluca; Pollegioni, Loredano; Paradisi, Francesca

2017-01-01

An alcohol dehydrogenase from the halophilic archaeon Haloferax volcanii (HvADH2) has been engineered by rational design to broaden its substrate scope towards the conversion of a range of aromatic substrates, including flurbiprofenol, that is an intermediate of the non-steroidal anti-inflammatory drug, flurbiprofen. Wild-type HvADH2 showed minimal activity with flurbiprofenol (11.1 mU/mg). A homology model of HvADH2 was built and docking experiments with this substrate revealed that the biphenyl rings of flurbiprofenol formed strong interactions with residues F85 and F108, preventing its optimal binding in the active site. Mutations at position 85 however did not increase activity. Site directed mutagenesis at position F108 allowed the identification of three variants showing a significant (up to 2.3-fold) enhancement of activity towards flurbiprofenol, when compared to wild-type HvADH2. Interestingly, F108G variant did not show the classic inhibition in the presence of (R)-enantiomer when tested with rac-1-phenylethanol, underling its potential in racemic resolution of secondary alcohols.

Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

PubMed

Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

2018-04-01

The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

PubMed Central

Kabbage, Maria; Chahed, Karim; Hamrita, Bechr; Guillier, Christelle Lemaitre; Trimeche, Mounir; Remadi, Sami; Hoebeke, Johan; Chouchane, Lotfi

2008-01-01

Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, α-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues. PMID:18401453

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

PubMed

Coopey, Suzanne B; Mazzola, Emanuele; Buckley, Julliette M; Sharko, John; Belli, Ahmet K; Kim, Elizabeth M H; Polubriaginof, Fernanda; Parmigiani, Giovanni; Garber, Judy E; Smith, Barbara L; Gadd, Michele A; Specht, Michelle C; Guidi, Anthony J; Roche, Constance A; Hughes, Kevin S

2012-12-01

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

Prevalence and Correlation of Human Papilloma Virus and its Types with Prognostic Markers in Patients with Invasive Ductal Carcinoma of the Breast in Kuwait

PubMed Central

Francis, Issam M.; Al-Ayadhy, Bushra; Al-Awadhi, Shafiqa; Kapila, Kusum; Al-Mulla, Fahd

2013-01-01

Objectives: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. Methods: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. Results: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. Conclusion: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected. PMID:24273662

[Benign proliferative breast disease with and without atypia].

PubMed

Coutant, C; Canlorbe, G; Bendifallah, S; Beltjens, F

2015-12-01

In the last few years, diagnostics of high-risk breast lesions (atypical ductal hyperplasia [ADH], flat epithelial atypia [FEA], lobular neoplasia: atypical lobular hyperplasia [ALH], lobular carcinoma in situ [LCIS], radial scar [RS], usual ductal hyperplasia [UDH], adenosis, sclerosing adenosis [SA], papillary breast lesions, mucocele-like lesion [MLL]) have increased with the growing number of breast percutaneous biopsies. The management of these lesions is highly conditioned by the enlarged risk of breast cancer combined with either an increased probability of finding cancer after surgery, either a possible malignant transformation (in situ or invasive cancer), or an increased probability of developing cancer on the long range. An overview of the literature reports grade C recommendations concerning the management and follow-up of these lesions: in case of ADH, FEA, ALH, LCIS, RS, MLL with atypia, diagnosed on percutaneous biopsies: surgical excision is recommended; in case of a diagnostic based on vacuum-assisted core biopsy with complete disappearance of radiological signal for FEA or RS without atypia: surgical abstention is a valid alternative approved by multidisciplinary meeting. In case of ALH (incidental finding) associated with benign lesion responsible of radiological signal: abstention may be proposed; in case of UDH, adenosis, MLL without atypia, diagnosed on percutaneous biopsies: the concordance of radiology and histopathology findings must be ensured. No data is available to recommend surgery; in case of non-in sano resection for ADH, FEA, ALH, LCIS (except pleomorphic type), RS, MLL: surgery does not seem to be necessary; in case of previous ADH, ALH, LCIS: a specific follow-up is recommended in accordance with HAS's recommendations. In case of FEA and RS or MLL combined with atypia, little data are yet available to differ the management from others lesions with atypia; in case of UDH, usual sclerosing adenosis, RS without atypia, fibro cystic

Treatment of Ductal Carcinoma In Situ Among Patients Cared for in Large Integrated Health Plans

PubMed Central

Haque, Reina; Achacoso, Ninah S.; Fletcher, Suzanne W.; Nekhlyudov, Larissa; Collins, Laura C.; Schnitt, Stuart J.; Quesenberry, Charles P.; Habel, Laurel A.

2013-01-01

Objective To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. Study Design Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. Methods We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. χ2 Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. Results We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31–0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48–0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. Conclusion Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods. PMID:20469955

Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

PubMed

Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

2013-02-01

This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001).  MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts

Treatment decision-making in ductal carcinoma in situ: A mixed methods systematic review of women's experiences and information needs.

PubMed

Rutherford, Claudia; Mercieca-Bebber, Rebecca; Butow, Phyllis; Wu, Jenny Liang; King, Madeleine T

2017-09-01

Decision-making in ductal carcinoma in situ (DCIS) is complex due to the heterogeneity of the disease. This study aimed to understand women's experience of making treatment decisions for DCIS, their information and support needs, and factors that influenced decisions. We searched six electronic databases, conference proceedings, and key authors. Two reviewers independently applied inclusion and quality criteria, and extracted findings. Thematic analysis was used to combine and summarise findings. We identified six themes and 28 subthemes from 18 studies. Women with DCIS have knowledge deficits about DCIS, experience anxiety related to information given at diagnosis and the complexity of decision-making, and have misconceptions regarding risks and outcomes of treatment. Women's decisions are influenced by their understanding of risk, the clinical features of their DCIS, and the benefits and harms of treatment options. Women are dissatisfied with the decisional support available. Informed and shared decision-making in this complex decision setting requires clear communication of information specific to DCIS and individual's, as well as decision support for patients and clinicians. This approach would educate patients and clinicians, and assist clinicians in supporting patients to an evidence-based treatment plan that aligns with individual values and pReferences. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

ClinicalTrials.gov

2011-12-07

Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).

PubMed

Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio

2015-11-01

Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a

Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?

NASA Astrophysics Data System (ADS)

Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2017-03-01

Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic features to predict upstaging of DCIS. The goal was to provide intentionally conservative baseline performance using readily available data from radiologists and pathologists and only linear models. We conducted a retrospective analysis on 99 patients with DCIS. Of those 25 were upstaged to invasive cancer at the time of definitive surgery. Pre-operative factors including both the histologic features extracted from stereotactic core needle biopsy (SCNB) reports and the mammographic features annotated by an expert breast radiologist were investigated with statistical analysis. Furthermore, we built classification models based on those features in an attempt to predict the presence of an occult invasive component in DCIS, with generalization performance assessed by receiver operating characteristic (ROC) curve analysis. Histologic features including nuclear grade and DCIS subtype did not show statistically significant differences between cases with pure DCIS and with DCIS plus invasive disease. However, three mammographic features, i.e., the major axis length of DCIS lesion, the BI-RADS level of suspicion, and radiologist's assessment did achieve the statistical significance. Using those three statistically significant features as input, a linear discriminant model was able to distinguish patients with DCIS plus invasive disease from those with pure DCIS, with AUC-ROC equal to 0.62. Overall, mammograms used for breast screening contain useful information that can be perceived by radiologists and help predict occult invasive components in DCIS.

Isolation and Identification of Genes Activating Uas2-Dependent Adh2 Expression in Saccharomyces Cerevisiae

PubMed Central

Donoviel, M. S.; Young, E. T.

1996-01-01

Two cis-acting elements have been identified that act synergistically to regulate expression of the glucose-repressed alcohol dehydrogenase 2 (ADH2) gene. UAS1 is bound by the trans-activator Adr1p. UAS2 is thought to be the binding site for an unidentified regulatory protein. A genetic selection based on a UAS2-dependent ADH2 reporter was devised to isolate genes capable of activating UAS2-dependent transcription. One set of UAS2-dependent genes contained SPT6/CRE2/SSN20. Multicopy SPT6 caused improper expression of chromosomal ADH2. A second set of UAS2-dependent clones contained a previously uncharacterized open reading frame designated MEU1 (Multicopy Enhancer of UAS2). A frame shift mutation in MEU1 abolished its ability to activate UAS2-dependent gene expression. Multicopy MEU1 expression suppressed the constitutive ADH2 expression caused by cre2-1. Disruption of MEU1 reduced endogenous ADH2 expression about twofold but had no effect on cell viability or growth. No homologues of MEU1 were identified by low-stringency Southern hybridization of yeast genomic DNA, and no significant homologues were found in the sequence data bases. A MEU1/β-gal fusion protein was not localized to a particular region of the cell. MEU1 is linked to PPR1 on chromosome XII. PMID:8807288

Conditioning to ethanol in the fruit fly-a study using an inhibitor of ADH.

PubMed

Cadieu, N; Cadieu, J -C.; El Ghadraoui, L; Grimal, A; Lamboeuf, Y

1999-06-01

To identify processes involved in the choice of ethanol by adult Drosophila, flies homozygous Adh(F), reared in the absence of alcohol were placed in contact with: a) an ethanol-free medium, b) a medium containing ethanol, c) a medium supplemented with 4-methylpyrazole (4-MP, an inhibitor of the ADH pathway), d) a medium containing ethanol and 4-MP. The choice of ethanol over a medium without ethanol was evaluated by measuring the duration of extension of the proboscis of the flies in each of the media. A slight preference for the ethanol-supplemented medium was observed in the naive flies, which was enhanced by previous exposure to ethanol. Exposure to ethanol and 4-MP, however, led to an avoidance of ethanol. There was a reduction in ADH activity on treatment of the flies with 4-MP, and signs of malaise (reduced locomotor activity, loss of balance) were observed in the flies who ingested both ethanol and inhibitor. We concluded that the preference for ethanol stems from an associative learning related to ethanol utilization. Inhibition of enzymes of ADH pathway led to a conditioned aversion due to disturbance of ethanol metabolism giving rise to malaise.

Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism.

PubMed

Kimura, Mitsuru; Miyakawa, Tomohiro; Matsushita, Sachio; So, Mirai; Higuchi, Susumu

2011-11-01

Gender differences are known to exist in the prevalence, characteristics, and course of alcohol dependence. Elucidating gender differences in the characteristics of alcohol dependence is important in gender-based medicine and may improve treatment outcomes. Many studies have shown that genetic factors are associated with the risk of alcohol dependence in both genders. Polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are strong genetic determinants of alcohol dependence. This study aimed to clarify gender differences in the effects of ADH1B and ALDH2 polymorphism on the development of alcohol dependence. Subjects were 200 female alcoholics and 415 male alcoholics hospitalized in Kurihama Alcoholism Center. Clinical information and background data were obtained by chart review. ALDH2 and ADH1B genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. The onset age of female alcoholics with inactive ALDH2 genotype was significantly lower than those with active ALDH2 genotype, but the onset age did not differ between the inactive and active ALDH2 group in male alcoholics. The difference in onset age between the ADH1B genotype groups did not reach significant levels. The prevalence of comorbid psychiatric disorders, including major depression, eating disorder, panic disorder, and borderline personality disorder, was significantly higher in female alcoholics with inactive ALDH2 or superactive ADH1B than in those with active ALDH2 or normal ADH1B. ALDH2 polymorphism appears to have contrasting effects on the development of alcoholism in women and men. One possible reason for this gender difference may be the high prevalence of psychiatric comorbidities in female alcoholics with inactive ALDH2. Copyright © 2011 by the Research Society on Alcoholism.

Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma.

PubMed

Iwaya, Keiichi; Norio, Kohno; Mukai, Kiyoshi

2007-03-01

Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the

Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2017-11-15

Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

Temperature and water loss affect ADH activity and gene expression in grape berry during postharvest dehydration.

PubMed

Cirilli, Marco; Bellincontro, Andrea; De Santis, Diana; Botondi, Rinaldo; Colao, Maria Chiara; Muleo, Rosario; Mencarelli, Fabio

2012-05-01

Clusters of Aleatico wine grape were picked at 18°Brix and placed at 10, 20, or 30°C, 45% relative humidity (RH) and 1.5m/s of air flow to dehydrate the berries up to 40% of loss of initial fresh weight. Sampling was done at 0%, 10%, 20%, 30%, and 40% weight loss (wl). ADH (alcohol dehydrogenase) gene expression, enzyme activity, and related metabolites were analysed. At 10°C, acetaldehyde increased rapidly and then declined, while ethanol continued to rise. At 20°C, acetaldehyde and ethanol increased significantly with the same pattern and declined at 40%wl. At 30°C, acetaldehyde did not increase but ethanol increased rapidly already at 10%wl. At the latter temperature, a significant increase in acetic acid and ethyl acetate occurred, while at 10°C their values were low. At 30°C, the ADH activity (ethanol to acetaldehyde direction), increased rapidly but acetaldehyde did not rise because of its oxidation to acetic acid, which increased together with ethyl acetate. At 10°C, the ADH activity increased at 20%wl and continued to rise even at 40%wl, meaning that ethanol oxidation was delayed. At 20°C, the behaviour was intermediate to the other temperatures. The relative expression of the VvAdh2 gene was the highest at 10°C already at 10%wl in a synchrony with the ADH activity, indicating a rapid response likely due to low temperature. The expression subsequently declined. At 20 and 30°C, the expression was lower and increased slightly during dehydration in combination with the ADH activity. This imbalance between gene expression and ADH activity at 10°C, as well as the unexpected expression of the carotenoid cleavage dioxygenase 1 (CCD1) gene, opens the discussion on the stress sensitivity and transcription event during postharvest dehydration, and the importance of carefully monitoring temperature during dehydration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of the pancreas.

PubMed

Lane, R B; Sangüeza, O P

1997-05-01

Anaplastic carcinomas of the pancreas are considered variants of ductal adenocarcinoma. They typically occur in elderly men. They have rarely been reported to occur in association with mucinous cystic neoplasms of the pancreas. We report a case of anaplastic carcinoma occurring in association with a pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who presented with lymph node and hepatic metastases.

Retinoblastoma and Phosphate and Tensin Homolog Tumor Suppressors: Impact on Ductal Carcinoma In Situ Progression

PubMed Central

2012-01-01

Background A subset of patients with ductal carcinoma in situ (DCIS) will progress to invasive breast cancer. However, there are currently no markers to differentiate women at high risk from those at lower risk of developing invasive disease. Methods The association of two major tumor suppressor genes, retinoblastoma (RB) and phosphatase and tensin homolog (PTEN), with risk of any ipsilateral breast event (IBE) or progression to invasive breast cancer (IBC) was analyzed using data from 236 DCIS patients treated with breast conserving surgery with long-term follow-up. RB and PTEN expression was assessed with immunohistochemistry. The functional effects of RB and/or PTEN loss were modeled in MCF10A cells. Hazard ratios (HRs) were estimated with univariate and multivariable Cox regression models. All statistical tests were two-sided. Results Loss of RB immunoreactivity in DCIS was strongly associated with risk of IBE occurrence (HR = 2.64; 95% confidence interval [CI] = 1.64 to 4.25) and IBC recurrence (HR = 4.66; 95% CI = 2.19 to 9.93). The prognostic power of RB loss remained statistically significant in multivariable analyses. PTEN loss occurred frequently in DCIS but was not associated with recurrence or progression. However, patients with DCIS lesions that were both RB and PTEN deficient were at further increased risk for IBEs (HR = 3.39; 95% CI = 1.92 to 5.99) and IBC recurrence (HR = 6.1, 95% CI = 2.5 to 14.76). Preclinical modeling in MCF10A cells demonstrated that loss of RB and PTEN impacted proliferation, motility, and invasive properties. Conclusions These studies indicate that RB and PTEN together have prognostic utility and could be used to target aggressive treatment for patients with the greatest probability of benefit. PMID:23197489

Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ.

PubMed

Beguinot, Marie; Dauplat, Marie-Melanie; Kwiatkowski, Fabrice; Lebouedec, Guillaume; Tixier, Lucie; Pomel, Christophe; Penault-Llorca, Frederique; Radosevic-Robin, Nina

2018-02-03

Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS). We retrospectively investigated TIL density and immunophenotype in 96 pure DCIS and 35 microinvasive carcinomas (miCa). TIL density was assessed on H&E-stained breast biopsy sections as the percentage of tumour stromal area occupied by TILs, and classified into 4 grades: 0 (0%-9%), 1 (10-29%), 2 (30-49%) and 3 (50%-100%). TIL immunophenotype was assessed by immunohistochemistry for CD8, CD4, FoxP3, CD38 or CD20. Compared to pure DCIS, miCa contained significantly more cases with TIL density grade 3 (p = 0.028). Concordantly, CD8+, CD4+ and CD38+ cells were more numerous in miCa than in pure DCIS. In the pure DCIS subgroup with TIL density grades 2 and 3, all TIL subpopulations were more numerous than in the pure DCIS with TIL density grades 0 and 1, however the ratio between T-lymphocytes (CD8+ and CD4+) and B-lymphocytes (CD20+) was significantly lower (p = 0.029). On the other side, this ratio was significantly higher in miCa, in comparison with pure DCIS having TIL density grades 2 and 3 (p = 0.017). By cluster analysis of tumour cell pathobiological features we demonstrated similarity between miCa and the pure DCIS with TIL density grades 2 and 3. The only significant difference between those two categories was in the ratio of T- to B-TILs, higher in miCa. Results indicate that TIL density level can distinguish 2 biologically different DCIS subgroups, one of which (DCIS with ≥30% TILs, the TIL-rich DCIS) is like miCa. Similarity of TIL-rich pure DCIS and miCa as well as the role of B-lymphocytes in DCIS invasiveness are worth further investigating with

Distinction of Invasive Carcinoma Derived From Intraductal Papillary Mucinous Neoplasms From Concomitant Ductal Adenocarcinoma of the Pancreas Using Molecular Biomarkers.

PubMed

Tamura, Koji; Ohtsuka, Takao; Date, Kenjiro; Fujimoto, Takaaki; Matsunaga, Taketo; Kimura, Hideyo; Watanabe, Yusuke; Miyazaki, Tetsuyuki; Ohuchida, Kenoki; Takahata, Shunichi; Ishigami, Kousei; Oda, Yoshinao; Mizumoto, Kazuhiro; Nakamura, Masafumi; Tanaka, Masao

2016-07-01

To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC). Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients. KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components. It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management.

Predictive values of BI-RADS(®) magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS).

PubMed

Badan, Gustavo Machado; Piato, Sebastião; Roveda, Décio; de Faria Castro Fleury, Eduardo

2016-10-01

The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

PubMed

Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

2010-11-01

Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

Diagnosis and management of ductal carcinoma in situ (DCIS).

PubMed

Virnig, Beth A; Shamliyan, Tatyana; Tuttle, Todd M; Kane, Robert L; Wilt, Timothy J

2009-09-01

Systematic synthesis of the published evidence about incidence, risk factors, and management options for women with ductal carcinoma in situ (DCIS) of the breast. Original epidemiologic studies were sought from several databases to identity articles published in English between 1970 and January 31, 2009. Incidence of DCIS in the general population and among women at greater risk of breast cancer and patient outcomes after diagnostic magnetic resonance imaging (MRI) or sentinel lymph node biopsy (SLNB) were abstracted into the developed standardized form. Patient outcomes after breast conserving surgery with or without adjuvant radio- or chemotherapy or after mastectomy were compared from randomized controlled clinical trials (RCTs) and observational studies. Three hundred seventy-four publications were eligible for the review. Rarely diagnosed before 1980, the incidence of DCIS increased by 270 percent since 1987 to 37.5 per 100,000 women in 2001, partially due to increased use of mammography with no good evidence of overdiagnosis (63 publications). Incidence was higher with increasing age, breast density, and family history and lower among physically active women and aspirin users (29 publications). Tamoxifen did not prevent DCIS at longer followup in women at high risk of breast cancer (two RCTs). No good evidence was identified around the optimal use of MRI for treatment planning (64 publications). Case-series from academic centers reported that around 5 percent of women with final histological diagnosis of DCIS had positive sentinel nodes and 1 percent were upgraded to metastatic cancer with no significant differences in outcomes (50 publications). Good evidence from five RCTs (ten publications) suggested that breast conserving surgery with adjuvant radiation reduced ipsilateral (the same breast) tumors by 53 percent with no differences in mortality or contralateral (the second breast) cancer. One RCT demonstrated that adjuvant chemotherapy reduced ipsilateral

ADH1B*2 allele is protective against alcoholism but not chronic liver disease in the Hungarian population.

PubMed

Toth, Reka; Pocsai, Zsuzsa; Fiatal, Szilvia; Szeles, Gyorgy; Kardos, Laszlo; Petrovski, Beata; McKee, Martin; Adany, Roza

2010-05-01

Standardized death rates from chronic liver diseases (CLDs) in Hungary are much higher than the European Union average. Carrying the alcohol dehydrogenase 1B 48His allele (rs1229984 or ADH1B*2) could decrease the risk of alcoholism, but with persistent drinking may confer a greater risk of CLDs. The aim of this study was to assess the prevalence of this polymorphism in the Hungarian population and its association with alcohol consumption and with CLDs. A total of 278 cases with diagnosed CLDs and 752 controls without any alterations in liver function, all males aged 45-64, were screened for ADH1B Arg48His polymorphism. ADH1B*2 allele frequencies in controls and cases were 8.31% and 4.50%, respectively (chi(2) = 9.2; P = 0.01). Carrying the ADH1B*2 allele was associated with significantly lower odds ratio (OR) for drinking frequency (OR = 0.63; P = 0.003), the number of positive answers on CAGE (Cut-down, Annoyed, Guilt, Eye-opener) assessment (OR = 0.58; P = 0.005) and a positive CAGE status (OR = 0.55; P = 0.007). There was a significant association between ADH1B*2 and CLDs (OR = 0.50; P = 0.003), but it disappeared after adjusting for CAGE status and scores (OR = 0.67 P = 0.134; OR = 0.67 P = 0.148, respectively) and weakened after adjusting for drinking frequency (OR = 0.61; P = 0.045). Among heavy drinkers the presence of ADH1B*2 did not increase the risk of cirrhosis but there was a significant interaction between genotype and CAGE status (P = 0.003, P = 0.042), with ADH1B*2 conferring reduced risk of CLDs in CAGE negatives. In Hungarians, the ADH1B 48His allele reduces the risk of alcoholism, but not the risk of chronic liver disease among heavy drinkers.

Emerging Trends in Surgical and Adjuvant Radiation Therapies among Women Diagnosed with Ductal Carcinoma in Situ

PubMed Central

Shiyanbola, Oyewale O.; Sprague, Brian L.; Hampton, John M.; Dittus, Kim; James, Ted A.; Herschorn, Sally; Gangnon, Ronald E.; Weaver, Donald L.; Trentham-Dietz, Amy

2016-01-01

BACKGROUND The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. We sought to investigate recent patterns in DCIS treatment by demographic factors. METHODS Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group and geographic region. The likelihood of receiving specific treatment modalities was analyzed using multivariable logistic regression. RESULTS DCIS cases were most frequently treated with breast conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation following BCS plateaued at around 70% after 2007, with increasing utilization of mastectomy beyond 2005. Additionally, there was an increasing trend in post-mastectomy reconstruction over time, and women of African ancestry (odds ratio, 0.69; 95% confidence interval,0.66–0.72) and Hispanic women were less likely to undergo reconstruction (odds ratio, 0.83; 95% confidence interval, 0.78–0.89) compared to women of European ancestry. A similar trend was observed in contralateral risk reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk reducing mastectomy among all ancestral/ethnic groups. CONCLUSION Recent trends demonstrate a plateau in radiation therapy administration following BCS, with increasing utilization of mastectomy, reconstruction and contralateral risk reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. PMID:27244699

Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy.

PubMed

Catteau, Xavier; Simon, Philippe; Noël, Jean-Christophe

2012-04-15

15±30% of malignancies detected through screening programs are ductal carcinoma in situ (DCIS), and the majority of DCIS cases present in the form of mammographic microcalcification. This study was performed in order to determine the value of features in predicting invasive disease in patients with mammographic calcification and to help determine which patients (with, Core Needle Biopsy-diagnosed DCIS) are the most appropriate candidates for Sentinel Lymph Node (SLN) biopsy. The original aspect of this study was to select patients with mammographic microcalcification but without an associated mass. The factor that we identified to be associated with invasive disease at final surgical excision was the presence of necrosis at core histology. SLN biopsy or complete axillary lymph node dissection was performed in 22 (40%) patients of whom only one (4.5%) had a micrometastasis. Further larger studies are needed to see if it would be interesting to propose a SLN biopsy in case of necrosis on CNB-diagnosed DCIS with microcalcifications but not associated with a mass. Copyright © 2012 Elsevier GmbH. All rights reserved.

How different terminology for ductal carcinoma in situ (DCIS) impacts women's concern and management preferences: A qualitative study.

PubMed

Nickel, Brooke; Barratt, Alexandra; Hersch, Jolyn; Moynihan, Ray; Irwig, Les; McCaffery, Kirsten

2015-10-01

There are increasing rates of mastectomy and bi-lateral mastectomy in women diagnosed with ductal carcinoma in situ (DCIS). To help women avoid decisions that lead to unnecessary aggressive treatments, there have been recent calls to remove the cancer terminology from descriptions of DCIS. We investigated how different proposed terminologies for DCIS affect women's perceived concern and management preferences. Qualitative study using semi-structured interviews with a community sample of 26 Australian women varying by education and cancer screening experience. Women responded to a hypothetical scenario using terminology with and without the cancer term to describe DCIS. Among a sample of women with no experience of a DCIS diagnosis, a hypothetical scenario involving a diagnosis of DCIS elicited high concern regardless of the terminology used to describe it. Women generally exhibited stronger negative reactions when a cancer term was used to describe DCIS compared to a non-cancer term, and most preferred the diagnosis be given as a description of abnormal cells. Overall women expressed interest in watchful waiting for DCIS but displayed preferences for very frequent monitoring with this management approach. Communicating a diagnosis of DCIS using terminology that does not include the cancer term was preferred by many women and may enable discussions about more conservative management options. However, women's preference for frequent monitoring during watchful waiting suggests women need more education and reassurance about this management approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Subclinical ductal carcinoma in situ of the breast: treatment with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Roncadin, M; Coghetto, F; Valdagni, R; Fasan, S; Maluta, S; Di Marco, A; Neri, S; Vidali, C; Panizzoni, G; Aristei, C

1999-01-01

In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

Impact of Margin Status on Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Childs, Stephanie K.; Chen, Yu-Hui; Duggan, Margaret M.

Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location ofmore » the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted.« less

Angiotensin II inhibits ADH-stimulated cAMP: role on O2- and transport-related oxygen consumption in the loop of Henle.

PubMed

Silva, G B; Juncos, L I; Baigorria, S T; Garcia, N H

2013-01-01

Dehydration and acute reductions of blood pressure increases ADH and Ang II levels. These hormones increase transport along the distal nephron. In the thick ascending limb (TAL) ADH increases transport via cAMP, while Ang II acts via superoxide (O2-). However, the mechanism of interaction of these hormones in this segment remains unclear. The aim of this study was to explore ADH/Ang II interactions on TAL transport. For this, we measured the effects of ADH/Ang II, added sequentially to TAL suspensions from Wistar rats, on oxygen consumption (QO2) -as a transport index-, cAMP and O2-. Basal QO2 was 112+-5 nmol O2/min/mg protein. Addition of ADH (1nM) increased QO2 by 227 percent. In the presence of ADH, Ang II (1nM) elicited a QO2 transient response. During an initial 3.1+-0.7 minutes after adding Ang II, QO2 decreased 58 percent (p less than 0.03 initial vs. ADH) and then rose by 188 percent (p less than 0.03 late vs initial Ang II). We found that Losartan blocked the initial effects of Ang II and the latter blocked ADH and forskolin-stimulated cAMP. The NOS inhibitor L-NAME or the AT2 receptor antagonist PD123319 showed no effect on transported related oxygen consumption. Then, we assessed the late period after adding Ang II. The O2- scavenger tempol blocked the late Ang II effects on QO2, while Ang II increased O2- production during this period. We conclude that 1) Ang II has a transient effect on ADH-stimulated transport; 2) this effect is mediated by AT1 receptors; 3) the initial period is mediated by decreased cAMP and 4) the late period is mediated by O2-.

The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

PubMed

van Luijt, P A; Heijnsdijk, E A M; Fracheboud, J; Overbeek, L I H; Broeders, M J M; Wesseling, J; den Heeten, G J; de Koning, H J

2016-05-10

The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halasz, Lia M.; Sreedhara, Meera; Chen, Yu-Hui

2012-03-15

Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2{sup +} DCIS.more » Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR{sup +}HER-2{sup -}, 27 were ER/PR{sup +}HER-2{sup +}, 6 were ER{sup -}/PR{sup -}HER-2{sup +}, and 6 were ER{sup -}/PR{sup -}HER-2{sup -}. On univariable analysis, HER-2{sup +}was significantly associated with Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2{sup +}. Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors

Mucinous breast carcinoma with tall columnar cells.

PubMed

Tsoukalas, N; Kiakou, M; Tolia, M; Kostakis, I D; Galanopoulos, M; Nakos, G; Tryfonopoulos, D; Kyrgias, G; Koumakis, G

2018-05-01

Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases.

PubMed

Kashyap, Anamika; Jain, Manjula; Shukla, Shailaja; Andley, Manoj

2017-01-01

Breast cancer has emerged as a leading site of cancer among women in India. Fine needle aspiration cytology (FNAC) has been routinely applied in assessment of breast lesions. Cytological evaluation in breast lesions is subjective with a "gray zone" of 6.9-20%. Quantitative evaluation of nuclear size, shape, texture, and density parameters by morphometry can be of diagnostic help in breast tumor. To apply nuclear morphometry on cytological breast aspirates and assess its role in differentiating between benign and malignant breast lesions with derivation of suitable cut-off values between the two groups. The present study was a descriptive cross-sectional hospital-based study of nuclear morphometric parameters of benign and malignant cases. The study included 50 benign breast disease (BBD), 8 atypical ductal hyperplasia (ADH), and 64 carcinoma cases. Image analysis was performed on Papanicolaou-stained FNAC slides by Nikon Imaging Software (NIS)-Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included 5 nuclear size, 2 shape, 4 texture, and 2 density parameters. Nuclear morphometry could differentiate between benign and malignant aspirates with a gradually increasing nuclear size parameters from BBD to ADH to carcinoma. Cut-off values of 31.93 μm 2 , 6.325 μm, 5.865 μm, 7.855 μm, and 21.55 μm for mean nuclear area, equivalent diameter, minimum feret, maximum ferret, and perimeter, respectively, were derived between benign and malignant cases, which could correctly classify 7 out of 8 ADH cases. Nuclear morphometry is a highly objective tool that could be used to supplement FNAC in differentiating benign from malignant lesions, with an important role in cases with diagnostic dilemma.

Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

PubMed

Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

2015-01-01

Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

1984-01-01

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

Is ADH1C genotype relevant for the cardioprotective effect of alcohol?

PubMed

Høiseth, Gudrun; Magnus, Per; Knudsen, Gun Peggy; Jansen, Mona Dverdal; Næss, Oyvind; Tambs, Kristian; Mørland, Jørg

2013-03-01

The cardioprotective effect of ethanol has been suggested to be linked to one of the ethanol metabolizing enzymes (ADH1C), which constitutes a high V(max) and a low V(max) variant. This has been demonstrated in some studies, while others have not been able to replicate the findings. The aim of the present study was to investigate the relation between the different ADH1C genotypes, death from coronary heart disease (CHD) and alcohol in a material larger than the previously published studies. Eight hundred CHD deaths as well as 1303 controls were genotyped for the high V(max) (γ1) and the low V(max) (γ2) ADH1C variant. Information of alcohol use was available for all subjects. Multiple logistic regression analyses was used to study if the decreased risk of death from CHD in alcohol consuming subjects was more pronounced in subjects homozygous for the γ2 allele (γ2γ2 subjects) compared to γ1γ1 and γ1γ2 subjects. The odds ratio (OR) for death from CHD in alcohol consumers compared to abstainers was similar in the genotype groups, i.e., 0.62 (95% CI: 0.43-0.88) in γ1γ1 subjects and 0.62 (95% CI: 0.42-0.91) in γ2γ2 subjects. Also when stratifying the results by gender and when dividing alcohol consumers into different alcohol consumption groups, there was no difference in the OR between the different genotype groups. This study, which included the largest study group published so far, failed to find any link between the ADH1C genotype and the cardioprotective effects of alcohol. Copyright © 2013 Elsevier Inc. All rights reserved.

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

PubMed

Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P; Thürlimann, Beat; Gelber, Richard D; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N; Regan, Meredith M; Coates, Alan S; Goldhirsch, Aron

2015-09-01

To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. © 2015 by American Society of Clinical Oncology.

Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55-74 years of age.

PubMed

Li, Christopher I; Daling, Janet R; Haugen, Kara L; Tang, Mei Tzu Chen; Porter, Peggy L; Malone, Kathleen E

2014-06-01

The Women's Health Initiative (WHI) randomized trials found that use of combined estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer risk, but use of unopposed estrogen hormone therapy (EHT) does not. However, several questions regarding the impact of hormone use on risk of different types of breast cancer and what thresholds of use confer elevations in risk remain. We conducted a population-based case-control study among women 55-74 years of age to assess the association between menopausal hormone use and risk of invasive ductal and invasive lobular breast carcinomas. Associations were evaluated using polytomous logistic regression and analyses included 880 ductal cases, 1,027 lobular cases, and 856 controls. Current EHT and CHT use were associated with 1.6-fold [95 % confidence interval (CI): 1.1-2.2] and 2.3-fold (95 % CI: 1.7-3.2) increased risks of lobular breast cancer, respectively, but neither was associated with risk of ductal cancer. Lobular cancer risk was increased after 9 years of EHT use, but after only 3 years of CHT use. Evidence across more than a dozen studies indicates that lobular carcinoma is the type of breast cancer most strongly influenced by menopausal hormones. Here, we characterize what thresholds of duration of use of both EHT and CHT that confer elevations in risk. Despite the rapid decline in hormone therapy use the WHI results were published, study of the hazards associated with these medications remains relevant given the estimated 38 million hormone therapy prescriptions that are still filled in the United States annually.

Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast-Report of two cases and literature review.

PubMed

Panse, Gauri; Bossuyt, Veerle; Ko, Christine J

2018-03-01

Non-mammary metastases involving breast are rare and most commonly involve the breast parenchyma. Infrequently, metastasis from an extramammary primary site presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can be challenging, especially in patients with coexisting primary breast carcinoma. Few such cases have been described in literature; however, none of the previously reported cases had a prior history of primary breast carcinoma. We present 2 patients with history of breast carcinoma and serous carcinoma of ovarian/peritoneal origin that presented with inflammatory carcinoma over the breast. Biopsies from breast tissue showed atypical cells in the dermis forming cords and papillary structures. Histopathologic differential diagnosis included infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma. Immunohistochemical studies showed that the tumor cells were positive for markers of ovarian origin such as PAX-8 and CA-125 and negative for breast markers such as GATA-3, thus supporting the diagnosis. In summary, we describe the unusual presentation of metastatic serous carcinoma as inflammatory carcinoma over breast and discuss the diagnostic challenges in patients with coexisting primary breast and ovarian malignancies. We also review the morphologic features of tumors of breast and ovarian origin and the immunohistochemical stains to differentiate these 2 entities. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

PubMed

Shiyanbola, Oyewale O; Sprague, Brian L; Hampton, John M; Dittus, Kim; James, Ted A; Herschorn, Sally; Gangnon, Ronald E; Weaver, Donald L; Trentham-Dietz, Amy

2016-09-15

The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society. © 2016 American Cancer Society.

A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

NASA Astrophysics Data System (ADS)

Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

2017-03-01

Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

Functional characterization of SlscADH1, a fruit-ripening-associated short-chain alcohol dehydrogenase of tomato.

PubMed

Moummou, Hanane; Tonfack, Libert Brice; Chervin, Christian; Benichou, Mohamed; Youmbi, Emmanuel; Ginies, Christian; Latché, Alain; Pech, Jean-Claude; van der Rest, Benoît

2012-10-15

A tomato short-chain dehydrogenase-reductase (SlscADH1) is preferentially expressed in fruit with a maximum expression at the breaker stage while expression in roots, stems, leaves and flowers is very weak. It represents a potential candidate for the formation of aroma volatiles by interconverting alcohols and aldehydes. The SlscADH1 recombinant protein produced in Escherichia coli exhibited dehydrogenase-reductase activity towards several volatile compounds present in tomato flavour with a strong preference for the NAD/NADH co-factors. The strongest activity was observed for the reduction of hexanal (K(m)=0.175mM) and phenylacetaldehyde (K(m)=0.375mM) in the presence of NADH. The oxidation process of hexanol and 1-phenylethanol was much less efficient (K(m)s of 2.9 and 23.0mM, respectively), indicating that the enzyme preferentially acts as a reductase. However activity was observed only for hexanal, phenylacetaldehyde, (E)-2-hexenal and acetaldehyde and the corresponding alcohols. No activity could be detected for other aroma volatiles important for tomato flavour, such as methyl-butanol/methyl-butanal, 5-methyl-6-hepten-2-one/5-methyl-6-hepten-2-ol, citronellal/citronellol, neral/nerol, geraniol. In order to assess the function of the SlscADH1 gene, transgenic plants have been generated using the technique of RNA interference (RNAi). Constitutive down-regulation using the 35S promoter resulted in the generation of dwarf plants, indicating that the SlscADH1 gene, although weakly expressed in vegetative tissues, had a function in regulating plant development. Fruit-specific down-regulation using the 2A11 promoter had no morphogenetic effect and did not alter the aldehyde/alcohol balance of the volatiles compounds produced by the fruit. Nevertheless, SlscADH1-inhibited fruit unexpectedly accumulated higher concentrations of C5 and C6 volatile compounds of the lipoxygenase pathway, possibly as an indirect effect of the suppression of SlscADH1 on the catabolism of

Primary Neuroendocrine Breast Carcinoma in a 13-Year-Old Girl: Ultrasonography and Pathology Findings

PubMed Central

Folligan, Koué; Sabi, Akomola; Sonhaye, Lantam; Boumé, Azanledji; Bassowa, Akila; Adani-Ifé, Solange; Napo-Koura, Gado

2017-01-01

Neuroendocrine carcinoma (NEC) of the breast is a rare disease and has been scarcely reported by African authors. The authors report a case of breast NEC in a 13-year-old African girl initially diagnosed as an atypical adenofibroma by ultrasonography. Ultrasound-guided biopsy and conventional histological examination indicated two potential diagnoses: primary malignant non-Hodgkin's lymphoma and undifferentiated carcinoma. According to immunohistochemistry performed on paraffin blocks in France, infiltrating ductal carcinoma with a strong neuroendocrine component was confirmed by CD56, CD57, and chromogranin A markers. PMID:29082059

Atypia on breast core needle biopsies: reproducibility and significance.

PubMed

Darvishian, Farbod; Singh, Baljit; Simsir, Aylin; Ye, Weimin; Cangiarella, Joan F

2009-01-01

This study analyzes the interobserver variability in interpreting atypia on breast core needle biopsies and in each category of atypia calculates the upgrade risk of carcinoma in the subsequent surgical excision. We identified 51 cases of atypia on breast core needle biopsies performed at our institution from January 2003 to August 2006. The atypia was classified into 4 categories: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and atypia of undetermined significance (AUS). After a tutorial session, these cases were independently reviewed by four pathologists, whose overall multi-rater kappa value for agreement on different categories of atypia was 0.79 (95% CI, 0.69-0.89), which is within the substantial agreement range. The upgrade risk in each category of atypia was as follows: ADH 20% (p = 0.04); ALH 10% (p = 0.6); FEA 16.6% (p = 0.23), and AUS 100% (p = 0.96). Based on our findings, we conclude that follow-up excision should be performed after a diagnosis of ADH. The upgrade risk did not reach statistical significance in ALH or FEA. Although follow-up excision cannot be strongly recommended in ALH and FEA, it should be considered since the upgrade risk is not negligible. Strict adherence to the diagnostic criteria and tutorial sessions can help pathologists to achieve substantial agreement in interpreting atypia on breast core needle biopsies.

CvADH1, a member of short-chain alcohol dehydrogenase family, is inducible by gibberellin and sucrose in developing watermelon seeds.

PubMed

Kim, Joonyul; Kang, Hong-Gyu; Jun, Sung-Hoon; Lee, Jinwon; Yim, Jieun; An, Gynheung

2003-01-01

To understand the molecular mechanisms that control seed formation, we selected a seed-preferential gene (CvADH1) from the ESTs of developing watermelon seeds. RNA blot analysis and in situ localization showed that CvADH1 was preferentially expressed in the nucellar tissue. The CvADH1 protein shared about 50% homology with short-chain alcohol dehydrogenase including ABA2 in Arabidopsis thaliana, stem secoisolariciresinol dehydrogenase in Forsythia intermedia, and 3beta-hydroxysterol dehydrogenase in Digitalis lanata. We investigated gene-expression levels in seeds from both normally pollinated fruits and those made parthenocarpic via N-(2-chloro-4-pyridyl)-N'-phenylurea treatment, the latter of which lack zygotic tissues. Whereas the transcripts of CvADH1 rapidly started to accumulate from about the pre-heart stage in normal seeds, they were not detectable in the parthenocarpic seeds. Treating the parthenogenic fruit with GA(3) strongly induced gene expression, up to the level accumulated in pollinated seeds. These results suggest that the CvADH1 gene is induced in maternal tissues by signals made in the zygotic tissues, and that gibberellin might be one of those signals. We also observed that CvADH1 expression was induced by sucrose in the parthenocarpic seeds. Therefore, we propose that the CvADH1 gene is inducible by gibberellin, and that sucrose plays an important role in the maternal tissues of watermelon during early seed development.

Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS).

PubMed

Chen, Youdinghuan; Marotti, Jonathan D; Jenson, Erik G; Onega, Tracy L; Johnson, Kevin C; Christensen, Brock C

2017-08-01

The utility and reliability of assessing molecular biomarkers for translational applications on pre-operative core biopsy specimens assume consistency of molecular profiles with larger surgical specimens. Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. DNA was extracted from guided 2mm cores of formalin fixed paraffin embedded (FFPE) specimens, bisulfite-modified, and measured on the Illumina HumanMethylation450 BeadChip. DNA methylation profiles of core biopsies exhibited high concordance with matched surgical specimens. Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P<2.20E-16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P<0.05). Between patient-matched core biopsy and surgical specimens, <0.6% of CpGs measured had changes in median DNA methylation >15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study.

PubMed

Solin, Lawrence J; Gray, Robert; Hughes, Lorie L; Wood, William C; Lowen, Mary Ann; Badve, Sunil S; Baehner, Frederick L; Ingle, James N; Perez, Edith A; Recht, Abram; Sparano, Joseph A; Davidson, Nancy E

2015-11-20

To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. © 2015 by American Society of Clinical Oncology.

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

Recent advances in genomic profiling of adenosquamous carcinoma of the pancreas.

PubMed

Marcus, Rebecca; Maitra, Anirban; Roszik, Jason

2017-11-01

Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole-genome and -exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP. Laser capture microdissection revealed that adenocarcinoma and squamous carcinoma components of ASCP harbor similar genomic variations, indicating that the origin of tumor components is the same or similar. Although the study published by Fang et al. increases our knowledge of this rare mixed tumor type, further investigation, including RNA sequencing, will be needed to fully characterize this malignancy and to aid the development of novel treatment approaches. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Differentiation of Ductal Carcinoma In-Situ from Benign Micro-Calcifications by Dedicated Breast Computed Tomography

PubMed Central

Shakeri, Shadi A.; Abbey, Craig K.; Gazi, Peymon; Prionas, Nicolas; Nosratieh, Anita; Li, Chin-Shang; Boone, John M.; Lindfors, Karen K.

2015-01-01

Purpose Compare conspicuity of ductal carcinoma in-situ (DCIS) to benign calcifications on unenhanced (bCT), contrast-enhanced dedicated breast CT (CEbCT) and mammography (DM). Methods and Materials The institutional review board approved this HIPAA-compliant study. 42 women with Breast Imaging Reporting and Data System 4 or 5 category micro-calcifications had breast CT before biopsy. Three subjects with invasive disease at surgery were excluded. Two breast radiologists independently compared lesion conspicuity scores (CS) for CEbCT, to bCT and DM. Enhancement was measured in Hounsfield units (HU). Mean CS ± standard deviations are shown. Receiver operating characteristic analysis (ROC) measured radiologists’ discrimination performance by comparing CS to enhancement alone. Statistical measurements were made using ANOVA F-test, Wilcoxon rank-sum test and robust linear regression analyses. Results 39 lesions (17 DCIS, 22 benign) were analyzed. DCIS (8.5±0.9, n=17) was more conspicuous than benign micro-calcifications (3.6±2.9, n=22; p<0.0001) on CEbCT. DCIS was equally conspicuous on CEbCT and DM (8.5±0.9, 8.7±0.8, n=17; p=0.85) and more conspicuous when compared to bCT (5.3±2.6, n=17; p<0.001). All DCIS enhanced; mean enhancement (90HU ±53HU, n=17) was higher compared to benign lesions (33 ±30HU, n=22)(p<0.0001). ROC analysis of the radiologists’ CS showed high discrimination performance (AUC=0.94) compared to enhancement alone (AUC=0.85) (p<0.026). Conclusion DCIS is more conspicuous than benign micro-calcifications on CEbCT. DCIS visualization on CEbCT is equal to mammography but improved compared to bCT. Radiologists’ discrimination performance using CEBCT is significantly higher than enhancement values alone. CEbCT may have an advantage over mammography by reducing false positive examinations when calcifications are analyzed. PMID:26520874

Facteurs prédictifs de l’adhésion médicamenteuse chez les patients en insuffisance cardiaque chronique: expérience marocaine

PubMed Central

Ragbaoui, Yassine; Nouamou, Imad; Hammiri, Ayoub El; Habbal, Rachida

2017-01-01

L’adhésion médicamenteuse chez les patients ayant une insuffisance cardiaque chronique est reconnue comme l’un des problèmes majeurs dans la gestion de cette pathologie. L’état démographique et socioéconomique des pays africains peut avoir un impact sur l’adhésion au traitement de l’insuffisance cardiaque chronique. Nous avons réalisé une étude transversale de Septembre 2014 à Janvier 2015 portant sur les patients en insuffisance cardiaque chronique suivis au centre d’insuffisance cardiaque du département de cardiologie du centre hospitalier universitaire IBN ROCHD à Casablanca au Maroc. La mesure de l’adhésion médicamenteuse était basée sur un questionnaire: questionnaire CARDIA. Les informations relatifs aux facteurs prédictifs d’adhésion médicamenteuse était dérivés du model d’adhésion multidimensionnel. Nous avons inclus dans cette étude 147 patients insuffisants cardiaques chroniques. Le pourcentage de l’adhésion médicamenteuse était de 83.6% selon CARDIA-Questionary. Les facteurs prédictifs qui influencent significativement l’adhésion médicamenteuse était: La dépression (p=0.034), le niveau de support social (p=0.03) et la prise de médicaments par le patient lui-même (p=0.0001). Comme dans plusieurs régions au monde, l’adhésion médicamenteuse chez les patients ayant une insuffisance cardiaque chronique reste un problème de santé au Maroc. Les différentes stratégies qui agissent sur les facteurs prédictifs pourraient améliorer l’adhésion médicamenteuse. PMID:28533838

Ensuring excision of intraductal lesions: marker placement at time of ductography.

PubMed

Woodward, Suzanne; Daly, Caroline P; Patterson, Stephanie K; Joe, Annette I; Helvie, Mark A

2010-11-01

To propose grid coordinate marker placement for patients with suspicious ductogram findings occult on routine workup. To compare the success of marker placement and wire localization (WL) with ductogram-guided WL. A retrospective search of radiology records identified all patients referred for ductography between January 2001 and May 2008. Results for 16 patients referred for ductogram-guided WL and 5 patients with grid coordinate marker placement at the time of ductography and subsequent WL were reviewed. Surgical pathology results and clinical follow-up were reviewed for concordance. Nine of 16 patients (56.3%) underwent successful ductogram-guided WL. Eight of nine patients had papillomas, one of which also had atypical ductal hyperplasia (ADH). One of nine patients had ectatic ducts with inspisated debris. Seven patients who failed ductogram-guided WL eventually underwent open surgical biopsy. Four of seven patients had papillomas, one of which also had lobular carcinoma in situ. Remaining patients had ADH (1/7) and fibrocystic changes with chronic inflammation (3/7). All five (100%) patients with grid coordinate marker placement underwent successful WL and marker excision. Pathology results included three papillomas, papillary intraductal hyperplasia, and fibrocystic change. Grid coordinate marker placement at the time of abnormal ductogram provided an accurate method of localizing ductal abnormalities that are occult on routine workup, thus facilitating future WL. Marker placement obviated the need for repeat ductogram on the day of surgery and ensured surgical removal of the ductogram abnormality. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

The yeast ADH7 promoter enables gene expression under pronounced translation repression caused by the combined stress of vanillin, furfural, and 5-hydroxymethylfurfural.

PubMed

Ishida, Yoko; Nguyen, Trinh Thi My; Izawa, Shingo

2017-06-20

Lignocellulosic biomass conversion inhibitors such as vanillin, furfural, and 5-hydroxymethylfurfural (HMF) inhibit the growth of and fermentation by Saccharomyces cerevisiae. A high concentration of each fermentation inhibitor represses translation and increases non-translated mRNAs. We previously reported that the mRNAs of ADH7 and BDH2, which encode putative NADPH- and NADH-dependent alcohol dehydrogenases, respectively, were efficiently translated even with translation repression in response to severe vanillin stress. However, the combined effects of these fermentation inhibitors on the expression of ADH7 and BDH2 remain unclear. We herein demonstrated that exposure to a combined stress of vanillin, furfural, and HMF repressed translation. The protein synthesis of Adh7, but not Bdh2 was significantly induced under combined stress conditions, even though the mRNA levels of ADH7 and BDH2 were up-regulated. Additionally, adh7Δ cells were more sensitive to the combined stress than wild-type and bdh2Δ cells. These results suggest that induction of the ADH7 expression plays a role in the tolerance to the combined stress of vanillin, furfural, and HMF. Furthermore, we succeeded in improving yeast tolerance to the combined stress by controlling the expression of ALD6 with the ADH7 promoter. Our results demonstrate that the ADH7 promoter can overcome the pronounced translation repression caused by the combined stress of vanillin, furfural, and HMF, and also suggest a new gene engineering strategy to breed robust and optimized yeasts for bioethanol production from a lignocellulosic biomass. Copyright © 2017 Elsevier B.V. All rights reserved.

First description and evaluation of SNPs in the ADH and ALDH genes in a population of alcoholics in Central-West Brazil.

PubMed

Teixeira, Thallita Monteiro; da Silva, Hugo Delleon; Goveia, Rebeca Mota; Ribolla, Paulo Eduardo Martins; Alonso, Diego Peres; Alves, Alessandro Arruda; Melo E Silva, Daniela; Collevatti, Rosane Garcia; Bicudo, Lucilene Arilho; Bérgamo, Nádia Aparecida; de Paula Silveira-Lacerda, Elisângela

2017-12-01

Worldwide, different studies have reported an association of alcohol-use disorder (AUD) with different types of Single Nucleotide Polymorphisms (SNPs) in the genes for aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH). In Brazil, there is little information about the occurrence of these SNPs in the AUD population and an absence of studies characterizing the population in the Central-West Region of Brazil. Actually, in Brazil, there are more than 4 million people with AUD. Despite the major health hazards of AUD, information on alcohol consumption and its consequences are not well understood. Therefore, it is extremely important to characterize these SNPs for the better understanding of AUD as a genetic disease in the Brazilian population. The present study, unlike other studies in other countries, is done with a subject population that shows a significant amount of racial homogenization. We evaluated the presence of SNPs in the ADH (ADH1B, ADH1C, and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás - Brazil, and then we established a possible relationship with AUD by allelic and genotypic study. This study was conducted with a population of people with AUD (n = 99) from Goiás Alcohol Dependence Recovery Center (GO CEREA) and Psychosocial Care Center for Alcohol and Drugs (CAPS AD), and with a population of people without AUD as controls (n = 100). DNA was extracted from whole-blood samples and the genotyping was performed using TaqMan ® SNP genotyping assays. For characterization and evaluation of SNPs in the population, genotype frequency, allele frequency, haplotype frequency, Hardy-Weinberg equilibrium, and linkage disequilibrium were analyzed. Statistical analyses were calculated by GENEPOP 4.5 and Haploview software. The allele 1 was considered as "wild" (or *1) and allele 2 as mutant (or *2). Significant differences were found for ADH1B*, ADH4*2, and ALDH2*2 SNPs when the genotype and allele frequencies were

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial

PubMed Central

Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P.; Thürlimann, Beat; Gelber, Richard D.; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N.; Regan, Meredith M.; Coates, Alan S.; Goldhirsch, Aron

2015-01-01

Purpose To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients and Methods Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor–positive with high (luminal B [LB] –like) or low (luminal A [LA] –like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. Results The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). Conclusion The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. PMID:26215945

Molecular evolution of Adh and LEAFY and the phylogenetic utility of their introns in Pyrus (Rosaceae)

PubMed Central

2011-01-01

Background The genus Pyrus belongs to the tribe Pyreae (the former subfamily Maloideae) of the family Rosaceae, and includes one of the most important commercial fruit crops, pear. The phylogeny of Pyrus has not been definitively reconstructed. In our previous efforts, the internal transcribed spacer region (ITS) revealed a poorly resolved phylogeny due to non-concerted evolution of nrDNA arrays. Therefore, introns of low copy nuclear genes (LCNG) are explored here for improved resolution. However, paralogs and lineage sorting are still two challenges for applying LCNGs in phylogenetic studies, and at least two independent nuclear loci should be compared. In this work the second intron of LEAFY and the alcohol dehydrogenase gene (Adh) were selected to investigate their molecular evolution and phylogenetic utility. Results DNA sequence analyses revealed a complex ortholog and paralog structure of Adh genes in Pyrus and Malus, the pears and apples. Comparisons between sequences from RT-PCR and genomic PCR indicate that some Adh homologs are putatively nonfunctional. A partial region of Adh1 was sequenced for 18 Pyrus species and three subparalogs representing Adh1-1 were identified. These led to poorly resolved phylogenies due to low sequence divergence and the inclusion of putative recombinants. For the second intron of LEAFY, multiple inparalogs were discovered for both LFY1int2 and LFY2int2. LFY1int2 is inadequate for phylogenetic analysis due to lineage sorting of two inparalogs. LFY2int2-N, however, showed a relatively high sequence divergence and led to the best-resolved phylogeny. This study documents the coexistence of outparalogs and inparalogs, and lineage sorting of these paralogs and orthologous copies. It reveals putative recombinants that can lead to incorrect phylogenetic inferences, and presents an improved phylogenetic resolution of Pyrus using LFY2int2-N. Conclusions Our study represents the first phylogenetic analyses based on LCNGs in Pyrus

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

PubMed

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

Organoid Models of Human and Mouse Ductal Pancreatic Cancer

PubMed Central

Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

2015-01-01

SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

Biosynthetic burden and plasmid burden limit expression of chromosomally integrated heterologous genes (pdc, adhB) in Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, A.; York, S.W.; Yomano, L.P.

1999-10-01

Previous studies have shown an unexpectedly high nutrient requirement for efficient ethanol production by ethanologenic recombinants of Escherichia coli B such as LY01 which contain chromosomally integrated Zymomonas mobilis genes (pdc, adhB) encoding the ethanol pathway. The basis for this requirement has been identified as a media-dependent effect on the expression of the Z. mobilis genes rather than a nutritional limitation. Ethanol production was substantially increased without additional nutrients simply by increasing the level of pyruvate decarboxylase activity. This was accomplished by adding a multicopy plasmid containing pdc alone (but not adhB alone) to strain LY01, and by adding multicopymore » plasmids which express pdc and adhB from strong promoters. New strong promoters were isolated from random fragments of Z. mobilis DNA and characterized but were not used to construct integrated biocatalysts. These promoters contained regions resembling recognition sites for 3 different E. coli sigma factors: {sigma}{sup 70}, {sigma}{sup 38}, and {sigma}{sup 28}. The most effective plasmid-based promoters for fermentation were recognized by multiple sigma factors, expressed both pdc and adhB at high levels, and produced ethanol efficiently while allowing up to 80% reduction in complex nutrients as compared to LY01. The ability to utilize multiple sigma factors may be advantageous to maintain the high levels of PDC and ADH needed for efficient ethanol production throughout batch fermentation.« less

Reduced MUC4 expression is a late event in breast carcinogenesis and is correlated with increased infiltration of immune cells as well as promoter hypermethylation in invasive breast carcinoma.

PubMed

Cho, Jin Seong; Park, Min Ho; Lee, Ji Shin; Yoon, Jung Han

2015-01-01

Altered expression of MUC4 is associated with tumor progression and immune surveillance, but the potential involvement of MUC4 in breast carcinogenesis has not been rigorously assessed. Immunohistochemical staining with anti-MUC4 antibody was performed in a total of 324 patients with 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 invasive breast carcinoma (IBC) using tissue microarray. Immunohistochemical staining for CD8, CD57, and CD1a and methylation-specific polymerase chain reaction were also performed in IBC. Reduced MUC4 expression in IBC was significantly higher than in usual ductal hyperplasia and ductal carcinoma in situ (P<0.001 and P<0.01, respectively). Reduced MUC4 expression in IBC was significantly correlated with promoter hypermethylation (P<0.05). No association between MUC4 expression and patient outcomes was identified. Intratumoral CD8 T cells and stromal CD57 natural killer cells were significantly increased in the reduced MUC4 expression group compared with those in the normal expression group (P<0.01 and P<0.05, respectively). Our results suggest that tumor progression in breast epithelium is accompanied by reduced MUC4 protein expression. Reduced MUC4 expression correlates with increased tumor-infiltrating CD8 T and NK cells as well as promoter hypermethylation in IBC.

Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases

PubMed Central

Kashyap, Anamika; Jain, Manjula; Shukla, Shailaja; Andley, Manoj

2017-01-01

Background: Breast cancer has emerged as a leading site of cancer among women in India. Fine needle aspiration cytology (FNAC) has been routinely applied in assessment of breast lesions. Cytological evaluation in breast lesions is subjective with a “gray zone” of 6.9–20%. Quantitative evaluation of nuclear size, shape, texture, and density parameters by morphometry can be of diagnostic help in breast tumor. Aims: To apply nuclear morphometry on cytological breast aspirates and assess its role in differentiating between benign and malignant breast lesions with derivation of suitable cut-off values between the two groups. Settings and Designs: The present study was a descriptive cross-sectional hospital-based study of nuclear morphometric parameters of benign and malignant cases. Materials and Methods: The study included 50 benign breast disease (BBD), 8 atypical ductal hyperplasia (ADH), and 64 carcinoma cases. Image analysis was performed on Papanicolaou-stained FNAC slides by Nikon Imaging Software (NIS)–Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included 5 nuclear size, 2 shape, 4 texture, and 2 density parameters. Results: Nuclear morphometry could differentiate between benign and malignant aspirates with a gradually increasing nuclear size parameters from BBD to ADH to carcinoma. Cut-off values of 31.93 μm2, 6.325 μm, 5.865 μm, 7.855 μm, and 21.55 μm for mean nuclear area, equivalent diameter, minimum feret, maximum ferret, and perimeter, respectively, were derived between benign and malignant cases, which could correctly classify 7 out of 8 ADH cases. Conclusion: Nuclear morphometry is a highly objective tool that could be used to supplement FNAC in differentiating benign from malignant lesions, with an important role in cases with diagnostic dilemma. PMID:28182052

Ethylene-responsive transcription factors interact with promoters of ADH and PDC involved in persimmon (Diospyros kaki) fruit de-astringency

PubMed Central

Min, Ting; Yin, Xue-ren; Chen, Kun-song

2012-01-01

The persimmon fruit is a particularly good model for studying fruit response to hypoxia, in particular, the hypoxia-response ERF (HRE) genes. An anaerobic environment reduces fruit astringency by converting soluble condensed tannins (SCTs) into an insoluble form. Although the physiology of de-astringency has been widely studied, its molecular control is poorly understood. Both CO2 and ethylene treatments efficiently removed the astringency from ‘Mopan’ persimmon fruit, as indicated by a decrease in SCTs. Acetaldehyde, the putative agent for causing de-astringency, accumulated during these treatments, as did activities of the key enzymes of acetaldehyde synthesis, alcohol dehydrogenase (ADH), and pyruvate decarboxylase (PDC). Eight DkADH and DkPDC genes were isolated, and three candidates for a role in de-astringency, DkADH1, DkPDC1, and DkPDC2, were characterized by transcriptional analysis in different tissues. The significance of these specific isoforms was confirmed by principal component analysis. Transient expression in leaf tissue showed that DkPDC2 decreased SCTs. Interactions of six hypoxia-responsive ERF genes and target promoters were tested in transient assays. The results indicated that two hypoxia-responsive ERF genes, DkERF9 and DkERF10, were involved in separately regulating the DkPDC2 and DkADH1 promoters. It is proposed that a DkERF–DkADH/DkPDC cascade is involved in regulating persimmon de-astringency. PMID:23095993

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Cytoplasmic involvement in ADH-mediated osmosis across toad urinary bladder.

PubMed

DiBona, D R

1983-11-01

Several lines of investigation have suggested that antidiuretic hormone (ADH) may have direct effects on the cytoskeletal organization of granular epithelial cells in the toad urinary bladder. To some extent, these effects are in concert with the well-established action of ADH on the hydraulic permeability of the mucosal plasma membrane, but it appears that other conformational adjustments (largely cytoplasmic) may be of comparable importance. The thrust of this review is that the hormone brings about a general restructuring of the granular cells so that the epithelium as a whole may function efficiently as an osmotic pathway. Details of cytoskeletal changes are far from clear as yet, but interference with or modulation of these particular effects infer that cytoplasmic organization is the seat of feedback control of osmotic flow rate, the basis for viability in the presence of dramatic cytosolic dilution and a major factor in the observed disparity in osmotic and diffusional permeability coefficients. In the interest of stimulating new thoughts and experiments in this area, a number of preliminary findings have been freely cited.

Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Arcicasa, M; Coghetto, F; Valdagni, R; Maluta, S; Di Marco, A

1997-09-01

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

Variations in the management of the axilla in screen-detected ductal carcinoma in situ: evidence from the UK NHS breast screening programme audit of screen detected DCIS.

PubMed

Nicholson, S; Hanby, A; Clements, K; Kearins, O; Lawrence, G; Dodwell, D; Bishop, H; Thompson, A

2015-01-01

The diagnosis and surgical management of screen-detected Ductal Carcinoma In Situ (DCIS) remains controversial including a range of axillary approaches and consequent morbidity. This study examined the management of the axilla in all patients with DCIS presenting through the United Kingdom National Health Service Breast Screening Programme (UK NHS BSP). Retrospective analysis of the UK NHS BSP identified 26,696 women initially diagnosed with DCIS over the 8 years 1 April 2003-31 March 2011. The final breast pathology of these women was upgraded to invasive ductal cancer in 5564 (20.8%) women or micro-invasive cancer in 1031 (3.9%) women. At first operation, 5290 (26.3%) of the 20,094 women who had a final post-operative diagnosis of DCIS only underwent axillary surgery (72.4% at the time of mastectomy, 23.8% breast conservation surgery, 3.8% axillary surgery alone). Performance of axillary surgery reflected increasing tumour size, micro-invasion or increasing nuclear grade for the final diagnosis of DCIS. More extensive nodal surgery was performed in those undergoing mastectomy; 10.8% of women had more than 8 nodes removed. Overall, 12.0% of women with invasive cancer, 1.7% with micro-invasion, and 0.2% with DCIS alone, were ultimately node positive. Improved pre-operative sampling of DCIS, axillary assessment by ultrasound with needle biopsy for suspected metastases, risk stratification for sentinel node biopsy (for high grade or extensive DCIS) and avoiding axillary clearance for a pre-operative diagnosis of DCIS alone should reduce unnecessary axillary surgery. Standards using such criteria for axillary surgery in screen-detected DCIS should be integrated into the NHS BSP. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

High diversity and no significant selection signal of human ADH1B gene in Tibet

PubMed Central

2012-01-01

Background ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP), rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on. Methods In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia. Results The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse) comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%). Luoba (2%) and Deng (0%) have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long-range haplotypes revealed

3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

ClinicalTrials.gov

2017-12-29

Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

Long-term results of conservative surgery and radiotherapy for ductal carcinoma in situ using lung density correction: the University of Michigan experience.

PubMed

Ben-David, Merav A; Sturtz, David E; Griffith, Kent A; Douglas, Kathye R; Hayman, James A; Lichter, Allen S; Pierce, Lori J

2007-01-01

The purpose of the study was to review the treatment outcomes of 198 patients treated with breast-conserving surgery (BCS) and whole breast radiation therapy using lung density correction for ductal carcinoma in situ (DCIS). Between April 1985 and December 2002, 198 patients with 200 lesions diagnosed as DCIS (AJCC stage 0) were treated at the University of Michigan. All underwent BCS and whole breast radiotherapy. Median total follow-up was 6.2 years (range: 0.8-18.2). The 5- and 10-year cumulative rates of in-breast only failure were 5.9% (95% CI: 2.6-9.3%) and 9.8% (95% CI: 5.2-14.4%), respectively. Factors that significantly predicted for an increased risk of local failure were family history of breast cancer, positive or close surgical margins and age

Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions

PubMed Central

Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

2011-01-01

Abstract Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies, as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3, PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. PMID:20132413

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer.

PubMed

Chiang, Chien-Ping; Jao, Shu-Wen; Lee, Shiao-Pieng; Chen, Pei-Chi; Chung, Chia-Chi; Lee, Shou-Lun; Nieh, Shin; Yin, Shih-Jiun

2012-02-01

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1>ALDH2>ADH3≈ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained

HER-2 amplification in tubular carcinoma of the breast.

PubMed

Oakley, Gerard J; Tubbs, Raymond R; Crowe, Joseph; Sebek, Bruce; Budd, G Thomas; Patrick, Rebecca J; Procop, Gary W

2006-07-01

The prognostic and therapeutic implications of HER-2 gene amplification and estrogen and progesterone receptor status in breast cancer are well described. To address the relative paucity of information concerning HER-2 amplification for tubular carcinomas, we assessed the frequency of gene amplification in 55 tubular carcinomas of the breast from 54 patients, 5 of which had axillary node metastases. The HER-2 gene copy number was assessed by fluorescence in situ hybridization for the majority of tumors analyzed, whereas estrogen and progesterone receptor status was achieved by immunohistochemical analysis. HER-2 gene amplification was not observed in any of the tumors examined, and most were estrogen receptor-positive. This HER-2 gene amplification frequency was significantly lower than the frequency of gene amplification previously reported for all invasive ductal carcinoma of no special type (P < .01). HER-2 gene amplification likely occurs infrequently, or not at all, in tubular carcinomas of the breast, whereas most express estrogen receptors.

Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

PubMed Central

Pour, P. M.; Weide, L.; Liu, G.; Kazakoff, K.; Scheetz, M.; Toshkov, I.; Ikematsu, Y.; Fienhold, M. A.; Sanger, W.

1997-01-01

To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined had the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9176407

How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey.

PubMed

McCaffery, Kirsten; Nickel, Brooke; Moynihan, Ray; Hersch, Jolyn; Teixeira-Pinto, Armando; Irwig, Les; Barratt, Alexandra

2015-11-02

There have been calls to remove 'carcinoma' from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as 'abnormal cells' versus 'pre-invasive breast cancer cells' on women's concern and treatment preferences. Community sample of Australian women (n=269) who spoke English as their main language at home. Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either 'abnormal cells' (arm A) or 'pre-invasive breast cancer cells' (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A ('abnormal cells' first term) indicated they would feel more concerned if given the alternative term ('pre-invasive breast cancer cells') compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from 'abnormal cells' to 'pre-invasive breast cancer cells' compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted women's concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards reducing overtreatment. Published by the BMJ Publishing Group Limited. For permission to use (where not

Opioid-induced hyponatremia in a patient with central diabetes insipidus: independence from ADH.

PubMed

Bhat, Nandini; Balliu, Erjola; Osipoff, Jennifer; Lane, Andrew; Wilson, Thomas

2017-05-24

Hyponatremia can be a complication of opioid therapy, which has been postulated to occur secondary to inappropriate antidiuretic hormone secretion (syndrome of inappropriate antidiuretic hormone secretion [SIADH]). We report severe hyponatremia following wisdom teeth extraction with opioid analgesia in a 19-year-old female with diabetes insipidus (DI) and acquired panhypopituitarism that challenges this theory. As this patient has DI, we believe opioid treatment caused severe hyponatremia by the following mechanisms: (1) Opioids have a direct antidiuretic effect independent of changes in ADH, as demonstrated in Brattleboro rats with central DI. (2) Hydrocodone may have stimulated this patient's thirst center contributing to hyponatremia, as demonstrated in animal studies. Opioid use can cause hyponatremia in patients independent of ADH. It is important for clinicians to be aware of this so that patients can be appropriately counseled.

[Vasopressin (ADH)].

PubMed

Hirai, A; Uchida, D; Yoshida, S

1992-12-01

Vasopressin is thought to play an important role, not only in the metabolism of water and electrolytes, but also in the regulation of renal hemodynamics. This year, great progress has been achieved in molecular biology of vasopressin receptors. First, the cloning of a complementary DNA, encoding the rat liver V1a arginine vasopressin receptor, was reported. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA, corresponding to the cDNA, is distributed in rat tissues, known to contain V1a receptors. Second, the cloning of a complementary DNA encoding the rat kidney V2 arginine vasopressin receptor was also successful. The kidney cDNA encodes a protein with a transmembrane topography characteristic of G protein-coupled receptors. The receptor messenger RNA is detected only in the kidney. Last year, an orally active and specific vasopressin V1 receptor antagonist, OPC-21268 was first reported. The i.v. or p.o. administration of OPC-21268 dose-dependently inhibited vasopressin-induced vasoconstriction, while that induced by angiotensin II was not affected. OPC-21268 may have clinical potentials in certain hypertensive cardiovascular disorders. In addition, an orally active and specific vasopressin V2 receptor antagonist, OPC-31260 was also reported. Oral administration of OPC-31260 inhibited antidiuretic action of arginine vasopressin. OPC-31260 is thought to be useful in the treatment of certain disorders, such as the syndrome of inappropriate secretion of ADH (SIADH).

Variation in detection of ductal carcinoma in situ (DCIS) during screening mammography A survey within the International Cancer Screening Network (ICSN)

PubMed Central

Lynge, Elsebeth; Ponti, Antonio; James, Ted; Májek, Ondřej; von Euler-Chelpin, My; Anttila, Ahti; Fitzpatrick, Patricia; Frigerio, Alfonso; Kawai, Masaaki; Scharpantgen, Astrid; Broeders, Mireille; Hofvind, Solveig; Vidal, Carmen; Ederra, Maria; Salas, Dolores; Bulliard, Jean-Luc; Tomatis, Mariano; Kerlikowske, Karla; Taplin, Stephen

2013-01-01

Background There is concern about detection of Ductal Carcinoma in Situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative analysis to determine variation in DCIS detection. Patients and Methods Data were collected during 2004–2008 on number of screening examinations, detected breast cancers, DCIS cases, and Globocan 2008 breast cancer incidence rates derived from national or regional cancer registers. We calculated screen-detection rates for breast cancers and DCIS. Results Data were obtained from 15 screening settings in 12 countries; 7,176,050 screening examinations; 29,605 breast cancers; and 5,324 DCIS cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95% confidence interval (CI) 2.76–3.00); 2.97 (95% CI 2.51–3.51) for detection of breast cancer; and 3.49 (95% CI 2.70–4.51) for detection of DCIS. Conclusions Considerable international variation was found in DCIS detection. This variation could not be fully explained by variation in incidence nor in breast cancer detection rates. It suggests the potential for wide discrepancies in management of DCIS resulting in overtreatment of indolent DCIS or undertreatment of potentially curable disease. Comprehensive cancer registration is needed to monitor DCIS detection. Efforts to understand discrepancies and standardize management may improve care. PMID:24041876

Biomarker Signatures of Mitochondrial NDUFS3 in Invasive Breast Carcinoma

PubMed Central

Suhane, Sonal; Berel, Dror; Ramanujan, V Krishnan

2011-01-01

We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma. PMID:21867691

Genome-Wide Significant Association between Alcohol Dependence and a Variant in the ADH Gene Cluster

PubMed Central

Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

2011-01-01

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification. PMID:22004471

Added Value of Breast MRI for Preoperative Diagnosis of Ductal Carcinoma In Situ: Diagnostic Performance on 362 Patients.

PubMed

Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Triunfo, Flavia; Filice, Salvatore; Vallone, Paolo; Setola, Sergio Venanzio; Rubulotta, Mariarosaria; Di Bonito, Maurizio; Rinaldo, Massimo; D'Aiuto, Massimiliano; Brunetti, Arturo

2017-06-01

The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer. A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann-Whitney U, χ 2 test, and Spearman correlation coefficient were performed. The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade. Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells*

PubMed Central

Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A.; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E.; Sipos, Bence; Baba, Hideo A.; Sitek, Barbara

2016-01-01

Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. PMID:26644413

Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature

PubMed Central

Marinova, Lena; Vicheva, Snezhinka

2016-01-01

We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status. PMID:27840759

Severe fatigue after treatment of ductal carcinoma in situ: A comparison with age-matched breast cancer survivors and healthy controls.

PubMed

Abrahams, H J G; Smits, L; Lugt, M de; Roos, W K de; Kamm, Y; Heins, M J; Verhagen, C A H H V M; Gielissen, M F M; Knoop, H

2017-02-01

Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

NASA Astrophysics Data System (ADS)

Shi, Bibo; Hou, Rui; Mazurowski, Maciej A.; Grimm, Lars J.; Ren, Yinhao; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2018-02-01

Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

What quality-of-life issues do women with ductal carcinoma in situ (DCIS) consider important when making treatment decisions?

PubMed

Mercieca-Bebber, Rebecca; King, Madeleine T; Boxer, Miriam M; Spillane, Andrew; Winters, Zoë E; Butow, Phyllis N; McPherson, Joan; Rutherford, Claudia

2017-09-01

To explore quality-of-life (QOL) issues considered important when deciding on treatment for ductal carcinoma in situ (DCIS). Breast Cancer Network of Australia members diagnosed with DCIS in the past 5 years (self-identified) participated in an online survey (Sep-Nov 2015). From a list of 74 QOL issues, participants selected all issues they experienced during DCIS diagnosis, treatment or recovery, then the issues they felt important to making a DCIS treatment decision, and completed the Health Literacy Questionnaire (HLQ). Associations between QOL issues and self-reported treatment received were assessed with χ 2 tests. The primary analysis included 38 participants treated with breast-conserving surgery (n = 15), mastectomy (n = 23), and/or radiotherapy (n = 14). Fatigue-related symptoms (82%) and "fear of progression" (50%) were the most frequently-experienced issues. When deciding on DCIS treatment, the most important consideration was "fear of progression" (50%). A higher proportion of mastectomy (compared to non-mastectomy) patients considered "difficultly looking at yourself naked" (p = 0.03). Radiotherapy (compared to non-radiotherapy) patients were more likely to consider "feeling unwell" important (p = 0.006). Results were similar in a sensitivity analysis involving all 101 respondents (i.e., including 63 respondents who reported receiving chemotherapy, endocrine therapy, and/or Herceptin, suggesting that they may have been treated for invasive breast cancer). Health literacy was high across all nine HLQ scales. Fear of progression is a key consideration in DCIS treatment decision making for women with high health literacy. QOL treatment considerations differed by treatments received. Women diagnosed with DCIS may benefit from evidence about QOL to inform treatment decision making.

Breast cancer: complete response with the combination of sunitinib and trastuzumab in a patient with grade III ductal carcinoma.

PubMed

Puente, Javier; Manzano, Aranzazu; Martin, Miguel; López-Tarruella, Sonia; Díaz-Rubio, Eduardo

2010-01-01

In August 2000, a previously healthy postmenopausal 52-year-old woman was diagnosed with grade III invasive ductal carcinoma. The tumor had an ER -, PR -, and HER2 + profile. Adjuvant treatment with FEC was initiated followed by radiotherapy. In October 2004, the patient presented a clinically asymptomatic supraclavicular and mediastinal lymph node recurrence and treatment with paclitaxel and trastuzumab was initiated. A complete response was achieved after 20 weeks of treatment, and in January 2006 treatment was interrupted due to toxicity. After a 34-month free-of-relapse period, a local recurrence was detected in the chest wall. In September 2007, the patient joined a phase II trial with sunitinib (37.5 mg once a day in 28 days cycles) and trastuzumab (6 mg/kg every 3 weeks), after having verified a normal cardiac function. After two courses, a partial cutaneous response and a complete radiological response were obtained. The most relevant toxicities included cutaneous hyperpigmentation, dysgeusia, mucositis, grade II diarrhea and hypertension. The development of grade III diarrhea led to sunitinib dose reduction (25mg/day). In January 2008, the patient developed hypothyroidism and a significant drop in the left ventricular ejection fraction that led to treatment interruption. In March 2008, once cardiac function was recovered, treatment at the same dose was reinitiated. After two months of treatment, a new descent in cardiac function was noted which led to the suspension of sunitinib, and the interruption of the trastuzumab treatment until recovery of normal cardiac function. In July 2008, trastuzumab monotherapy was resumed and since then no cardiac events have been reported, while maintaining a radiological and clinical response.

Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells.

PubMed

Al-Adsani, Amani; Burke, Zoë D; Eberhard, Daniel; Lawrence, Katherine L; Shen, Chia-Ning; Rustgi, Anil K; Sakaue, Hiroshi; Farrant, J Mark; Tosh, David

2010-10-27

The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype. These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ.

Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

ClinicalTrials.gov

2017-09-25

Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: preliminary data

NASA Astrophysics Data System (ADS)

Zhu, Zhe; Harowicz, Michael; Zhang, Jun; Saha, Ashirbani; Grimm, Lars J.; Hwang, Shelley; Mazurowski, Maciej A.

2018-02-01

Approximately 25% of patients with ductal carcinoma in situ (DCIS) diagnosed from core needle biopsy are subsequently upstaged to invasive cancer at surgical excision. Identifying patients with occult invasive disease is important as it changes treatment and precludes enrollment in active surveillance for DCIS. In this study, we investigated upstaging of DCIS to invasive disease using deep features. While deep neural networks require large amounts of training data, the available data to predict DCIS upstaging is sparse and thus directly training a neural network is unlikely to be successful. In this work, a pre-trained neural network is used as a feature extractor and a support vector machine (SVM) is trained on the extracted features. We used the dynamic contrast-enhanced (DCE) MRIs of patients at our institution from January 1, 2000, through March 23, 2014 who underwent MRI following a diagnosis of DCIS. Among the 131 DCIS patients, there were 35 patients who were upstaged to invasive cancer. Area under the ROC curve within the 10-fold cross-validation scheme was used for validation of our predictive model. The use of deep features was able to achieve an AUC of 0.68 (95% CI: 0.56-0.78) to predict occult invasive disease. This preliminary work demonstrates the promise of deep features to predict surgical upstaging following a diagnosis of DCIS.

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma.

PubMed

Yokoyama, Akira; Kato, Hoichi; Yokoyama, Tetsuji; Tsujinaka, Toshimasa; Muto, Manabu; Omori, Tai; Haneda, Tatsumasa; Kumagai, Yoshiya; Igaki, Hiroyasu; Yokoyama, Masako; Watanabe, Hiroshi; Fukuda, Haruhiko; Yoshimizu, Haruko

2002-11-01

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-2 (ADH2), ADH3, and glutathione S-transferase M1 (GSTM1) influence the metabolism of alcohol and other carcinogens. The ALDH2*1/2*2 genotype, which encodes inactive ALDH2, and ADH2*1/2*1, which encodes the low-activity form of ADH2, enhance the risk for esophageal cancer in East Asian alcoholics. This case-control study of whether the enzyme-related vulnerability for esophageal cancer can be extended to a general population involved 234 Japanese men with esophageal squamous cell carcinoma and 634 cancer-free Japanese men who received annual health checkups. The GSTM1 genotype was not associated with the risk for this cancer. Light drinkers (1-8.9 units/week) with ALDH2*1/2*2 had an esophageal cancer risk 5.82 times that of light drinkers with ALDH2*1/2*1 (reference category), and their risk was similar to that of moderate drinkers (9-17.9 units/week) with ALDH2*1/2*1 (odds ratio = 5.58). The risk for moderate drinkers with ALDH2*1/2*2 (OR = 55.84) exceeded that for heavy drinkers (18+ units/week) with ALDH2*1/2*1 (OR = 10.38). Similar increased risks were observed for those with ADH2*1/2*1. A multiple logistic model including ALDH2, ADH2, and ADH3 genotypes showed that the ADH3 genotype does not significantly affect the risk for esophageal cancer. For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11. In comparison with the estimated population-attributable risks for preference for strong alcoholic beverages (30.7%), smoking (53.6%) and for lower intake of green and yellow vegetables (25.7%) and fruit (37.6%), an extraordinarily high proportion of the excessive risk for esophageal cancer in the Japanese males can be attributed to drinking (90.9%), particularly drinking by persons with inactive heterozygous ALDH

Extracellular Ca2+ Sensing in Salivary Ductal Cells*

PubMed Central

Bandyopadhyay, Bidhan C.; Swaim, William D.; Sarkar, Ankana; Liu, Xibao; Ambudkar, Indu S.

2012-01-01

Ca2+ is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na+ and Cl− get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca2+] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca2+ remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca2+ reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca2+] or by aromatic amino acid, l-phenylalanine (l-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca2+ influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca2+ entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca2+ sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca2+] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca2+]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis). PMID:22778254

Molecular analysis of UAS(E), a cis element containing stress response elements responsible for ethanol induction of the KlADH4 gene of Kluyveromyces lactis.

PubMed

Mazzoni, C; Santori, F; Saliola, M; Falcone, C

2000-01-01

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity, which is specifically induced by ethanol and insensitive to glucose repression. In this work, we report the molecular analysis of UAS(E), an element of the KlADH4 promoter which is essential for the induction of KlADH4 in the presence of ethanol. UAS(E) contains five stress response elements (STREs), which have been found in many genes of Saccharomyces cerevisiae involved in the response of cells to conditions of stress. Whereas KlADH4 is not responsive to stress conditions, the STREs present in UAS(E) seem to play a key role in the induction of the gene by ethanol, a situation that has not been observed in the related yeast S. cerevisiae. Gel retardation experiments showed that STREs in the KlADH4 promoter can bind factor(s) under non-inducing conditions. Moreover, we observed that the RAP1 binding site present in UAS(E) binds KlRap1p.

Elevated Expression of IRS-1 Associates with p-Akt Expression and Predicts Poor Prognosis of Breast Invasive Ductal Carcinoma.

PubMed

Luo, Jiadi; Feng, Juan; Wen, Qiuyuan; Qoyawayma, Christopher; Wang, Weiyuan; Chen, Lingjiao; Lu, Junmi; Zhan, Yuting; Xu, Lina; Zang, Hongjing; Fan, Songqing; Chu, Shuzhou

2018-03-15

Overexpression of Insulin Receptor Substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis. And phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC is significantly higher than that in control breast tissue from non-cancer patients (P<.001, P=.001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt (r=.337, P<.001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P=.009). Furthermore, significantly worse overall survival was in BIDC patients with high expression of IRS-1 and p-Akt than patients with low expression (P=.006, P=.004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P=.022, P=.046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein associates with expression of p-Akt, and overexpression of IRS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC. Copyright © 2018. Published by Elsevier Inc.

Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population.

PubMed

Masaoka, Hiroyuki; Ito, Hidemi; Gallus, Silvano; Watanabe, Miki; Yokomizo, Akira; Eto, Masatoshi; Matsuo, Keitaro

2017-04-01

Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms are known to strongly influence alcohol　drinking behavior. Given evidence of an association between smoking and drinking behaviors, we hypothesized that ALDH2/ADH1B polymorphisms might also be associated with smoking initiation, and conducted a cross-sectional study to examine this hypothesis. Study subjects were first-visit outpatients diagnosed not to have cancer at Aichi Cancer Center Hospital between 2001 and 2005, including 4141 never smokers and 2912 ever smokers. Unconditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking initiation by comparing ever smokers with never smokers. Excessive alcohol drinking was associated with a higher likelihood of ever smoking. After adjustment for drinking behaviors, compared to individuals with ALDH2 Glu/Glu, the ORs of ever smoking were 1.71 (95% CI, 1.49-1.95) and 2.28 (1.81-2.87) among those with ALDH2 Glu/Lys and Lys/Lys, respectively. Combination of ALDH2 Lys/Lys and ADH1B His/His (i.e., the most alcohol-intolerant subpopulation) showed the highest OR [2.44 (1.84-3.23)], whereas combination of ALDH2 Glu/Glu and ADH1B Arg/Arg (i.e., the most alcohol-tolerant subpopulation) showed the lowest OR [0.83 (0.57-1.21)] compared with ALDH2 Glu/Glu and ADH1B His/His. Besides the amount and frequency of alcohol drinking, the combination of ALDH2 and ADH1B polymorphisms predicts smoking initiation. This study suggests that alcohol tolerance regulated by ALDH2 and ADH1B polymorphisms is associated with smoking initiation, and facilitates the development of targeted interventions to reduce smoking prevalence. Copyright © 2017 Elsevier B.V. All rights reserved.

Broccoli Sprout Extract in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-04

Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks

NASA Astrophysics Data System (ADS)

Cruz-Roa, Angel; Basavanhally, Ajay; González, Fabio; Gilmore, Hannah; Feldman, Michael; Ganesan, Shridar; Shih, Natalie; Tomaszewski, John; Madabhushi, Anant

2014-03-01

This paper presents a deep learning approach for automatic detection and visual analysis of invasive ductal carcinoma (IDC) tissue regions in whole slide images (WSI) of breast cancer (BCa). Deep learning approaches are learn-from-data methods involving computational modeling of the learning process. This approach is similar to how human brain works using different interpretation levels or layers of most representative and useful features resulting into a hierarchical learned representation. These methods have been shown to outpace traditional approaches of most challenging problems in several areas such as speech recognition and object detection. Invasive breast cancer detection is a time consuming and challenging task primarily because it involves a pathologist scanning large swathes of benign regions to ultimately identify the areas of malignancy. Precise delineation of IDC in WSI is crucial to the subsequent estimation of grading tumor aggressiveness and predicting patient outcome. DL approaches are particularly adept at handling these types of problems, especially if a large number of samples are available for training, which would also ensure the generalizability of the learned features and classifier. The DL framework in this paper extends a number of convolutional neural networks (CNN) for visual semantic analysis of tumor regions for diagnosis support. The CNN is trained over a large amount of image patches (tissue regions) from WSI to learn a hierarchical part-based representation. The method was evaluated over a WSI dataset from 162 patients diagnosed with IDC. 113 slides were selected for training and 49 slides were held out for independent testing. Ground truth for quantitative evaluation was provided via expert delineation of the region of cancer by an expert pathologist on the digitized slides. The experimental evaluation was designed to measure classifier accuracy in detecting IDC tissue regions in WSI. Our method yielded the best quantitative

Prognostic significance of hepatocyte growth factor activator inhibitor type 1 (HAI-1) immunoreactivity in pancreatic ductal adenocarcinoma.

PubMed

Sakugawa, Chihiro; Haruyama, Yukihiro; Tanaka, Hiroyuki; Fukushima, Tsuyoshi; Kawaguchi, Makiko; Kataoka, Hiroaki

2017-12-04

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial cells. Evidence has suggested that decreased cell surface HAI-1 in carcinoma cells results in enhanced invasiveness. However, little is known regarding the expression of HAI-1 in pancreatic ductal adenocarcinoma (PDAC). This study aimed to analyze HAI-1 expression in PDAC and its impact on patient prognosis. HAI-1 immunohistochemistry was performed on samples from 67 PDAC cases. HAI-1 expression was increased in intraepithelial neoplasia compared to the adjacent non-neoplastic ductal epithelium. Of the 67 samples tested, 58% (39/67) of PDAC cases showed diffuse (> 75%) immunoreactivity in PDAC cells. The remaining cases showed reduced HAI-1 immunoreactivity in a substantial number of cancer cells. Although there was no correlation between HAI-1 status and tumor size, histologic grade or lymph node metastasis, diffuse HAI-1 positive cases showed longer disease-free survival (DFS; p = 0.006, log-rank test). In conclusion, HAI-1 is upregulated in pancreatic intraepithelial neoplasia and broadly expressed in PDAC cells. However, PDAC cases having areas of reduced HAI-1 immunoreactivity may show shorter DFS.

SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

PubMed

Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

2016-10-01

Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

PubMed

Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

2017-12-01

There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

ClinicalTrials.gov

2017-06-07

Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

PubMed

Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

2013-09-01

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy.

PubMed

Huang, Nai-Si; Si, Jing; Yang, Ben-Long; Quan, Chen-Lian; Chen, Jia-Jian; Wu, Jiong

2018-01-01

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast-conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non-evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high-grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high-grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High-grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells.

PubMed

Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E; Sipos, Bence; Baba, Hideo A; Sitek, Barbara

2016-03-01

Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. © 2016 by The American Society for Biochemistry

Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer

ClinicalTrials.gov

2018-05-16

Atypical Ductal Breast Hyperplasia; Atypical Lobular Breast Hyperplasia; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; No Evidence of Disease

Anomalous pancreatico-biliary ductal union with cystic dilatation of the bile duct.

PubMed

Richer, J P; Faure, J P; Morichau-Beauchant, M; Dugue, T; Maillot, N; Kamina, P; Carretier, M

1998-01-01

We report, in an adult, an asymptomatic association between cystic dilation of the bile duct (type IV A in Todani's classification) and anomalous pancreatico-biliary ductal union (APBD) with stones in a long common channel. In APBD, the connection between the common bile duct and the main pancreatic duct is located outside the duodenal wall andis therefore not under the influence of the sphincter of Boyden. An abnormally long common channel is in excess of 15 mm. Two types of convergence anomalies are defined according to whether the bile duct opens into the main pancreatic duct (BP) or the main pancreatic duct into the bile duct (PB). In APBD, there is probably a reverse pressure gradient between the bile and pancreatic ducts, with regurgitation of pancreatic juice into the bile duct, repeated attacks of cholangitis, stenosis and cystic dilatation. A long common channel is associated with a higher incidence of carcinoma of the gall bladder of the bile duct.

Denture hyperplasia with areas simulating oral inverted ductal papilloma.

PubMed

Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

2005-07-01

Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

Mutational Analysis of the Adaptor Protein 2 Sigma Subunit (AP2S1) Gene: Search for Autosomal Dominant Hypocalcemia Type 3 (ADH3)

PubMed Central

Rogers, Angela; Nesbit, M. Andrew; Hannan, Fadil M.; Howles, Sarah A.; Gorvin, Caroline M.; Cranston, Treena; Allgrove, Jeremy; Bevan, John S.; Bano, Gul; Brain, Caroline; Datta, Vipan; Grossman, Ashley B.; Hodgson, Shirley V.; Izatt, Louise; Millar-Jones, Lynne; Pearce, Simon H.; Robertson, Lisa; Selby, Peter L.; Shine, Brian; Snape, Katie; Warner, Justin

2014-01-01

Context: Autosomal dominant hypocalcemia (ADH) types 1 and 2 are due to calcium-sensing receptor (CASR) and G-protein subunit-α11 (GNA11) gain-of-function mutations, respectively, whereas CASR and GNA11 loss-of-function mutations result in familial hypocalciuric hypercalcemia (FHH) types 1 and 2, respectively. Loss-of-function mutations of adaptor protein-2 sigma subunit (AP2σ 2), encoded by AP2S1, cause FHH3, and we therefore sought for gain-of-function AP2S1 mutations that may cause an additional form of ADH, which we designated ADH3. Objective: The objective of the study was to investigate the hypothesis that gain-of-function AP2S1 mutations may cause ADH3. Design: The sample size required for the detection of at least one mutation with a greater than 95% likelihood was determined by binomial probability analysis. Nineteen patients (including six familial cases) with hypocalcemia in association with low or normal serum PTH concentrations, consistent with ADH, but who did not have CASR or GNA11 mutations, were ascertained. Leukocyte DNA was used for sequence and copy number variation analysis of AP2S1. Results: Binomial probability analysis, using the assumption that AP2S1 mutations would occur in hypocalcemic patients at a prevalence of 20%, which is observed in FHH patients without CASR or GNA11 mutations, indicated that the likelihood of detecting at least one AP2S1 mutation was greater than 95% and greater than 98% in sample sizes of 14 and 19 hypocalcemic patients, respectively. AP2S1 mutations and copy number variations were not detected in the 19 hypocalcemic patients. Conclusion: The absence of AP2S1 abnormalities in hypocalcemic patients, suggests that ADH3 may not occur or otherwise represents a rare hypocalcemic disorder. PMID:24708097

Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast: A Trial of the Eastern Cooperative Oncology Group

PubMed Central

Hughes, Lorie L.; Wang, Molin; Page, David L.; Gray, Robert; Solin, Lawrence J.; Davidson, Nancy E.; Lowen, Mary Ann; Ingle, James N.; Recht, Abram; Wood, William C.

2009-01-01

Purpose To determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation. Patients and Methods Patients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively. Results With a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%). Conclusion Rigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results. PMID:19826126

Current treatment trends and the need for better predictive tools in the management of ductal carcinoma in situ of the breast.

PubMed

Martínez-Pérez, Carlos; Turnbull, Arran K; Ekatah, Gregory E; Arthur, Laura M; Sims, Andrew H; Thomas, Jeremy S; Dixon, J Michael

2017-04-01

Ductal carcinoma in situ (DCIS) of the breast represents a group of heterogeneous non-invasive lesions the incidence of which has risen dramatically since the advent of mammography screening. In this review we summarise current treatment trends and up-to-date results from clinical trials studying surgery and adjuvant therapy alternatives, including the recent consensus on excision margin width and its role in decision-making for post-excision radiotherapy. The main challenge in the clinical management of DCIS continues to be the tailoring of treatment to individual risk, in order to avoid the over-treatment of low-risk lesions or under-treatment of DCIS with higher risk of recurring or progressing into invasion. While studies estimate that only about 40% of DCIS would become invasive if untreated, heterogeneity and complex natural history have prevented adequate identification of these higher-risk lesions. Here we discuss attempts to develop prognostic tools for the risk stratification of DCIS lesions and their limitations. Early results of a UK-wide audit of DCIS management (the Sloane Project) have also demonstrated a lack of consistency in treatment. In this review we offer up-to-date perspectives on current treatment and prediction of DCIS, highlighting the pressing clinical need for better prognostic indices. Tools integrating both clinical and histopathological factors together with molecular biomarkers may hold potential for adequate stratification of DCIS according to risk. This could help develop standardised practices for optimal management of patients with DCIS, improving clinical outcomes while providing only the amount of therapy required for each individual patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): From microscopic measurements to macroscopic predictions of clinical progression

PubMed Central

Macklin, Paul; Edgerton, Mary E.; Thompson, Alastair M.; Cristini, Vittorio

2012-01-01

Ductal carcinoma in situ (DCIS)—a significant precursor to invasive breast cancer—is typically diagnosed as microcalcifications in mammograms. However, the effective use of mammograms and other patient data to plan treatment has been restricted by our limited understanding of DCIS growth and calcification. We develop a mechanistic, agent-based cell model and apply it to DCIS. Cell motion is determined by a balance of biomechanical forces. We use potential functions to model interactions with the basement membrane and amongst cells of unequal size and phenotype. Each cell’s phenotype is determined by genomic/proteomic- and microenvironment-dependent stochastic processes. Detailed “sub-models” describe cell volume changes during proliferation and necrosis; we are the first to account for cell calcification. We introduce the first patient-specific calibration method to fully constrain the model based upon clinically-accessible histopathology data. After simulating 45 days of solid-type DCIS with comedonecrosis, the model predicts: necrotic cell lysis acts as a biomechanical stress relief, and is responsible for the linear DCIS growth observed in mammography; the rate of DCIS advance varies with the duct radius; the tumour grows 7 to 10 mm per year—consistent with mammographic data; and the mammographic and (post-operative) pathologic sizes are linearly correlated—in quantitative agreement with the clinical literature. Patient histopathology matches the predicted DCIS microstructure: an outer proliferative rim surrounds a stratified necrotic core with nuclear debris on its outer edge and calcification in the centre. This work illustrates that computational modelling can provide new insight on the biophysical underpinnings of cancer. It may one day be possible to augment a patient’s mammography and other imaging with rigorously-calibrated models that help select optimal surgical margins based upon the patient’s histopathologic data. PMID:22342935

Identification of a G‐Protein Subunit‐α11 Gain‐of‐Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2)

PubMed Central

Piret, Sian E; Gorvin, Caroline M; Pagnamenta, Alistair T; Howles, Sarah A; Cranston, Treena; Rust, Nigel; Nesbit, M Andrew; Glaser, Ben; Taylor, Jenny C; Buchs, Andreas E; Hannan, Fadil M

2016-01-01

ABSTRACT Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia, inappropriately low serum parathyroid hormone concentrations and hypercalciuria. ADH is genetically heterogeneous with ADH type 1 (ADH1), the predominant form, being caused by germline gain‐of‐function mutations of the G‐protein coupled calcium‐sensing receptor (CaSR), and ADH2 caused by germline gain‐of‐function mutations of G‐protein subunit α‐11 (Gα11). To date Gα11 mutations causing ADH2 have been reported in only five probands. We investigated a multigenerational nonconsanguineous family, from Iran, with ADH and keratoconus which are not known to be associated, for causative mutations by whole‐exome sequencing in two individuals with hypoparathyroidism, of whom one also had keratoconus, followed by cosegregation analysis of variants. This identified a novel heterozygous germline Val340Met Gα11 mutation in both individuals, and this was also present in the other two relatives with hypocalcemia that were tested. Three‐dimensional modeling revealed the Val340Met mutation to likely alter the conformation of the C‐terminal α5 helix, which may affect G‐protein coupled receptor binding and G‐protein activation. In vitro functional expression of wild‐type (Val340) and mutant (Met340) Gα11 proteins in HEK293 cells stably expressing the CaSR, demonstrated that the intracellular calcium responses following stimulation with extracellular calcium, of the mutant Met340 Gα11 led to a leftward shift of the concentration‐response curve with a significantly (p < 0.0001) reduced mean half‐maximal concentration (EC50) value of 2.44 mM (95% CI, 2.31 to 2.77 mM) when compared to the wild‐type EC50 of 3.14 mM (95% CI, 3.03 to 3.26 mM), consistent with a gain‐of‐function mutation. A novel His403Gln variant in transforming growth factor, beta‐induced (TGFBI), that may be causing keratoconus was also identified, indicating likely digenic

Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

PubMed

Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

2017-05-01

We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

Harnessing 3D models of mammary epithelial morphogenesis. An off the beaten path approach to identify candidate biomarkers of early stage breast cancer

PubMed Central

Rossetti, Stefano; Bshara, Wiam; Reiners, Johanna A.; Corlazzoli, Francesca; Miller, Austin; Sacchi, Nicoletta

2016-01-01

Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8. Either ANXA2 downregulation or ANXA8 upregulation in the HME1 cell context are per se sufficient to confer a 3D DCIS-like morphology. Seemingly, different mutations impinged on a common mechanism that differentially regulates the two annexins. Second, we show that ANXA8 expression is significantly higher in DCIS tissue samples versus normal breast tissue and atypical ductal hyperplasia (ADH). Apparently, ANXA8 expression is significantly more upregulated in ER- negative versus ER-positive cases, and significantly correlates with tumor stage, grade and positive lymph node. Based on our study, 3D mammary morphogenesis models can be an alternate/complementary strategy for unraveling new DCIS mechanisms and biomarkers. PMID:27422542

Bioethanol production by heterologous expression of Pdc and AdhII in Streptomyces lividans.

PubMed

Lee, Jae Sun; Chi, Won-Jae; Hong, Soon-Kwang; Yang, Ji-Won; Chang, Yong Keun

2013-07-01

Two genes from Zymomonas mobilis that are responsible for ethanol production, pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adhII), were heterologously expressed in the Gram-positive bacterium Streptomyces lividans TK24. An examination of carbon distribution revealed that a significant portion of carbon metabolism was switched from biomass and organic acid biosynthesis to ethanol production upon the expression of pdc and adhII. The recombinant S. lividans TK24 produced ethanol from glucose with a yield of 23.7% based on the carbohydrate consumed. The recombinant was able to produce ethanol from xylose, L-arabinose, mannose, L-rhamnose, galactose, ribose, and cellobiose with yields of 16.0, 25.6, 21.5, 33.6, 30.6, 14.6, and 33.3%, respectively. Polymeric substances such as starch and xylan were directly converted to ethanol by the recombinant with ethanol yields of 18.9 and 8.8%, respectively. The recombinant S. lividans TK24/Tpet developed in this study is potentially a useful microbial resource for ethanol production from various sources of biomasses, especially microalgae.

Dynamically Coupled Food-web and Hydrodynamic Modeling with ADH-CASM

NASA Astrophysics Data System (ADS)

Piercy, C.; Swannack, T. M.

2012-12-01

Oysters and freshwater mussels are "ecological engineers," modifying the local water quality by filtering zooplankton and other suspended particulate matter from the water column and flow hydraulics by impinging on the near-bed flow environment. The success of sessile, benthic invertebrates such as oysters depends on environmental factors including but not limited to temperature, salinity, and flow regime. Typically food-web and other types of ecological models use flow and water quality data as direct input without regard to the feedback between the ecosystem and the physical environment. The USACE-ERDC has developed a coupled hydrodynamic-ecological modeling approach that dynamically couples a 2-D hydrodynamic and constituent transport model, Adaptive Hydraulics (ADH), with a bioenergetics food-web model, the Comprehensive Aquatics Systems Model (CASM), which captures the dynamic feedback between aquatic ecological systems and the environment. We present modeling results from restored oyster reefs in the Great Wicomico River on the western shore of the Chesapeake Bay, which quantify ecosystem services such as the influence of the benthic ecosystem on water quality. Preliminary results indicate that while the influence of oyster reefs on bulk flow dynamics is limited due to the localized influence of oyster reefs, large reefs and the associated benthic ecosystem can create measurable changes in the concentrations of nitrogen, phosphorus, and carbon in the areas around reefs. We also present a sensitivity analysis to quantify the relative sensitivity of the coupled ADH-CASM model to both hydrodynamic and ecological parameter choice.

The Genetics of a Small Autosomal Region of DROSOPHILA MELANOGASTER Containing the Structural Gene for Alcohol Dehydrogenase. I. Characterization of Deficiencies and Mapping of ADH and Visible Mutations

PubMed Central

Woodruff, R. C.; Ashburner, M.

1979-01-01

The position of the structural gene coding for alcohol dehydrogenase (ADH) in Drosophila melanogaster has been shown to be within polytene chromosome bands 35B1 and 35B3, most probably within 35B2. The genetic and cytological properties of twelve deficiencies in polytene chromosome region 34–35 have been characterized, eleven of which include Adh. Also mapped cytogenetically are seven other recessive visible mutant loci. Flies heterozygous for overlapping deficiencies that include both the Adh locus and that for the outspread mutant (osp: a recessive wing phenotype) are homozygous viable and show a complete ADH negative phenotype and strong osp phenotype. These deficiencies probably include two polytene chromosome bands, 35B2 and 35B3. PMID:115743

[Pathological and immunohistochemical analysis of giant cells of pancreas].

PubMed

Miyake, T; Suda, K; Yamamura, A; Tada, Y

1997-10-01

Multinucleated giant cells in the pancreas (five giant cell carcinomas, a mucinous cystadenocarcinoma attended with many osteoclast-like giant cells, 42 invasive ductal carcinomas and 29 chronic pancreatitises) were examined. Three types of multinucleated giant cell were identified: epithelial type, coexpressive type, mesenchymal type. Epithelial type expressed epithelial markers, such as keratin and EMA in 23 ductal carcinomas. Coexpressive type expressed both epithelial markers and mesenchymal marker vimentin was in four ductal carcinomas. Mesenchymal type expressed mesenchymal markers, vimentin and CD68 in four osteoclastoid type giant cell carcinomas, the mucinous cystadenocarcinoma, six ductal carcinomas and ten chronic pancreatitises. Epithelial and coexpressive type were considered to be epithelial neoplastic origin, those had bizarre appearance and transitional area from definite adenocarcinoma area. Vimentin expression is associated with sarcomatous proliferation. Mesenchymal type was considered to be nonneoplastic and a certain type of macrophage polykaryons.

Stiffness at shear-wave elastography and patient presentation predicts upgrade at surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma in situ.

PubMed

Evans, A; Purdie, C A; Jordan, L; Macaskill, E J; Flynn, J; Vinnicombe, S

2016-11-01

The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS). Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance. Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02). Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Flat epithelial atypia on core needle biopsy, must we surgically excise?

PubMed

Acott, A A; Mancino, A T

2016-12-01

Breast flat epithelial atypia (FEA) often coexists with more aggressive pathology and excision is currently recommended when diagnosed by core needle biopsy (CNB). Recent studies suggest isolated FEA has a low association with carcinoma and may warrant close surveillance. A radiology database containing 2189 breast CNB was reviewed for isolated FEA or FEA in combination with atypical pathology. 79 patients had FEA. There were 48/79 with isolated FEA and 31/79 concomitant FEA with ADH, ALH, or LCIS. 46 subsequent excisional biopsies of isolated FEA resulted: benign 38/46, ADH 5/46, LCIS 2/46, DCIS 1/46. Concomitant FEA + ADH/ALH/LCIS group resulted: benign 26/31, DCIS 3/31, DCIS and LCIS 1/31, tubular carcinoma 1/31. DCIS/invasive cancer on excision in the FEA + ADH group is 5/31 versus 1/46 for isolated FEA (p 0.0489). Findings support literature suggesting isolated FEA has a low association with carcinoma. These patients may not require surgical excision, but instead have close surveillance. Based on the higher cancer incidence in FEA combined with ADH, ALH, LCIS, or residual microcalcifications, we still recommend surgical excision. Breast flat epithelial atypia (FEA) often coexists with more aggressive pathology and surgical excision is currently recommended when diagnosed by core needle biopsy. Recent studies have suggested isolated FEA has a low association with carcinoma and these patients may warrant close surveillance. Isolated FEA has a low association with carcinoma in our series. These patients may not require surgical excision, but instead have close surveillance. Published by Elsevier Inc.

Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma

PubMed Central

Halaoui, Ruba; Rejon, Carlis; Chatterjee, Sudipa June; Szymborski, Joseph; Meterissian, Sarkis; Muller, William J.; Omeroglu, Atilla; McCaffrey, Luke

2017-01-01

Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical–basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization. PMID:28887414

Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

PubMed

Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

2017-12-08

Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci

Impact of the Level of Urothelial Carcinoma Involvement of the Prostate on Survival after Radical Cystectomy.

PubMed

Moschini, Marco; Soria, Francesco; Susani, Martin; Korn, Stephan; Briganti, Alberto; Roupret, Morgan; Seitz, Christian; Gust, Killian; Haitel, Andrea; Montorsi, Francesco; Wirth, Gregory; Robinson, Brian D; Karakiewicz, Pierre I; Özsoy, Mehmet; Rink, Michael; Shariat, Shahrokh F

2017-07-27

Urothelial prostatic involvement (UPI) at the time of radical cystoprostatectomy (RCP) was found associated with worse survival outcomes by several previous reports. Our aim is to evaluate the impact of different levels of UPI on survival outcomes using a large series of male patients treated with RCP. Whole step section specimens from 995 male BCa patients were assessed for UPI defined as: no involvement vs. prostatic urethral carcinoma in situ (CIS) vs. lamina propria involvement vs. ductal CIS vs. prostate stromal involvement. Primary end point of the study was predictors of prostatic involvement at RCP and its impact on overall survival after surgery. Prostatic involvement was recorded in 307 (30.9%) patients: 28% with prostatic urethral CIS, 12% with lamina propria involvement, 13% with ductal CIS and 47% with stromal involvement. Median follow-up was 70 months. Patients with stromal involvement had a worse 5-year survival (12%) than those with prostatic urethra CIS (40%), lamina propria involvement (36%), and ductal CIS (35%). Considering predictors of prostatic involvement, multifocal tumor (Odds Ratio [OR]: 6.60, p  < 0.001), lymphovascular invasion (OR: 2.61, p  < 0.001), lymph node metastases (OR: 2.02, p  < 0.001) and CIS (OR: 2.02, p  < 0.001) were found associated. Similar predictors were found assessing stromal involvement. Approximately one third of RCP patients harbor prostatic involvement of urothelial carcinoma. While all UPI are associated with worse overall survival, stromal involvement confers the worst outcome supporting its classification as T4 in the TNM staging.

Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis

PubMed Central

Chen, Wen-jun; Zhang, Xi; Wu, Cong-cong; Zhang, Chao-ying; Sun, Shuang-shuang; Wu, Jian

2017-01-01

Background There are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS. Results Radiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non-radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25. The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non-radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20. However, radiotherapy could not improve survival benefits, including overall survival, cancer-specific survival, breast-cancer-specific survival, and distant relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast events in older patients with DCIS. Materials and Methods PubMed and Embase database were searched for relevant studies. Hazard ratios (HRs), risk ratios (RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy in older patients. Conclusions Our study indicates that radiotherapy could slightly reduce the risk of local relapse in older patients with favorable early breast cancer. However, radiotherapy cannot translate into significant survival benefits. PMID:28415667

Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration.

PubMed

Horibata, Sachi; Rogers, Katherine E; Sadegh, David; Anguish, Lynne J; McElwee, John L; Shah, Pragya; Thompson, Paul R; Coonrod, Scott A

2017-05-26

Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development. Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland. Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF

Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

PubMed Central

2013-01-01

Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that

Pre- and Post-ductal oxygen saturation among apparently healthy low birth weight neonates.

PubMed

Odudu, Leo A; Ezenwa, Beatrice N; Esezobor, Christopher I; Ekure, Ekanem N; Egri Okwaji, Mathias T C; Ezeaka, Chinyere V; Njokanma, Fidelis O; Ladele, Jejelola

2017-01-01

Reference values of oxygen saturation (SpO2) to guide care of low birth weight neonates have been obtained mainly from Caucasians. Data from African newborns are lacking. To determine the pre- and post-ductal SpO2values of low birth weight neonates within the first 72 h of life, compare SpO2values of moderate-late preterm and term low birth weight neonates and determine how mode of delivery affected SpO2in the first 24 h of life. An observational descriptive study was carried out on apparently healthy low birth weight newborns weighing 1500 to ≤2499 g. Pre and post ductal SpO2values were recorded at the following hours of life: 10-24 h, >24-48 h and >48-72 h using a NONIN® pulse oximeter. The ranges of pre- and post-ductal SpO2in the study were similar for both preterm and term neonates in the study (89%-100%). The mean (standard deviation [SD]) pre-ductal SpO2was 95.9% (2.3) and the mean (SD) post-ductal SpO2was 95.9% (2.1). There was a significant increase in pre-ductal SpO2from 10 to 24 h through >48-72 h of life (P = 0.027). The mode of delivery did not affect SpO2values within 10-24 h of life. The present study documented daily single pre- and post-ductal SpO2 values for preterm and term low birth weight neonates weighing 1500 g to <2500 g during the first 72 h of life. The overall range and mean pre- and post-ductal SpO2 were similar for both categories of stable low birth weight neonates in the study. There was no significant difference between SpO2ranges for late preterm compared to term low birth weight neonates. The results obtained could serve as guide in assessing SpO2of low birth weight neonates weighing between 1500 and 2499 g in the first 72 h of life.

Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies.

PubMed

Calhoun, Benjamin C; Sobel, Amy; White, Richard L; Gromet, Matt; Flippo, Teresa; Sarantou, Terry; Livasy, Chad A

2015-05-01

Flat epithelial atypia of the breast commonly co-exists with atypical ductal hyperplasia, lobular neoplasia, and indolent forms of invasive carcinomas such as tubular carcinoma. Most patients with pure flat epithelial atypia on core biopsy undergo surgical excision to evaluate for carcinoma in the adjacent breast tissue. Studies to date have reported varying upgrade rates with most recommending follow-up excision. These studies have often lacked detailed radiographic correlation, central review by breast pathologists and information regarding the biology of the carcinomas identified upon excision. In this study, we report the frequency of upgrade to invasive carcinoma or ductal carcinoma in situ in excision specimens following a diagnosis of pure flat epithelial atypia on core biopsy. Radiographic correlation is performed for each case and grade/receptor status of detected carcinomas is reported. Seventy-three (73) core biopsies containing pure flat epithelial atypia were identified from our files, meeting inclusion criteria for the study. In the subsequent excision biopsies, five (7%) cases contained invasive carcinoma or ductal carcinoma in situ and seventeen (23%) contained atypical ductal hyperplasia or lobular neoplasia. All of the ductal carcinoma in situ cases with estrogen receptor results were estrogen receptor positive and intermediate grade. The invasive tumors were small (pT1a) hormone receptor-positive, HER2-negative, low-grade invasive ductal or tubular carcinomas with negative sentinel lymph-node biopsies. No upgrades were identified in the 14 patients who had all of their calcifications removed by the stereotactic core biopsy. Our rate of upgrade to carcinoma, once cases with discordant imaging are excluded, is at the lower end of the range reported in the literature. Given the low upgrade rate and indolent nature of the carcinomas associated with flat epithelial atypia, case management may be individualized based on clinical and radiographic

Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

PubMed

Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

2018-06-06

Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

Quantitative apparent diffusion coefficient as a noninvasive imaging biomarker for the differentiation of invasive breast cancer and ductal carcinoma in situ.

PubMed

Bickel, Hubert; Pinker-Domenig, Katja; Bogner, Wolfgang; Spick, Claudio; Bagó-Horváth, Zsuzsanna; Weber, Michael; Helbich, Thomas; Baltzer, Pascal

2015-02-01

The objective of this study was to evaluate whether apparent diffusion coefficient (ADC) obtained through diffusion-weighted imaging magnetic resonance imaging at 3 T can be used as an imaging biomarker to differentiate invasive breast cancer from noninvasive ductal carcinoma in situ (DCIS). One hundred seventy-six histopathologically verified primary malignant breast tumors were retrospectively evaluated in 170 patients. All patients had undergone a standardized 3-T magnetic resonance imaging protocol, containing a diffusion-weighted sequence with 2 b values and a series of dynamic contrast-enhanced T1-weighted sequences. Apparent diffusion coefficient was measured manually by a reader blinded to the histopathological results. The ADC values were correlated with histopathological results. Mean ADC values were compared between invasive cancers and DCIS as well as between different tumor grades. Receiver operating characteristics curves were used to calculate diagnostic performance. There were 155 invasive cancers and 21 noninvasive DCIS. Mean (SD) values differed significantly between the invasive cancers (0.9 [0.15] ×10 mm/s) and the DCIS (1.24 [0.23] ×10 mm/s, P < 0.001). Area under the receiver operating characteristics curve was 0.895 (95% confidence interval [CI], 0.840-0.936). A threshold of 1.01 ×10 mm/s or less allowed an identification of invasive cancers with a sensitivity of 78.06% (95% CI, 70.7%-84.3%) and a specificity of 90.5% (95% CI, 69.6%-98.8%). No significant ADC differences were found among different tumor grades (P > 0.05). Apparent diffusion coefficient could be used as an imaging biomarker for the diagnosis of breast cancer. It seems to be a valuable noninvasive quantitative biomarker to assess breast cancer invasiveness. Thus, ADC measurements provide the potential to reduce overdiagnosis and subsequent overtreatment.

GCDFP-15, AR, and Her-2 as biomarkers for primary ductal adenocarcinoma of the lacrimal gland: a Chinese case and literature review

PubMed Central

Zhu, Miao-Miao; Cui, Hong-Guang; Teng, Xiao-Dong

2015-01-01

Purpose Primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare malignant epithelial tumor, and its clinicopathological characteristics are still unclear. This study aimed to report a novel case of PDA of the lacrimal gland in the People’s Republic of China, as well as to determine its histopathological and immunohistochemical characteristics to support early diagnosis and direct further therapy. Patient and methods Clinical data (including ocular examination, computed tomography, magnetic resonance imaging, positron emission tomography, mammography, and serum tumor marker examination) and treatment of a 49-year-old woman with a left lacrimal gland mass, which was diagnosed as PDA of the lacrimal gland, were reported. Histopathological and immunohistochemical studies were performed. Eleven papers regarding this uncommon neoplasm were reviewed. Results Histopathologically, most of the tumor cells featured abundant granular eosinophilic cytoplasm, while few of them had a frothy appearance. The mass showed breast ductal carcinoma-like structural features, which most commonly demonstrated central necrosis, while less of these features showed cord-like infiltration. Immunohistochemically, the tumor cells were positive for GCDFP-15, CK 18 (++), AR (90%), Her-2 (+++), P53 (100%), and Ki-67 (with a proliferation index approximately 60%), while they were negative for ER, PR, P63, calponin, and CD 117. Conclusion This was the first Chinese case of PDA of the lacrimal gland that had been reported. We suggested that GCDFP-15, AR, and Her-2 should be tested as biomarkers for ductal adenocarcinoma of lacrimal gland to confirm diagnosis, guide therapy, and further predict prognosis. PMID:25999735

Treatment selection for patients with ductal carcinoma in situ (DCIS) of the breast using the University of Southern California/Van Nuys (USC/VNPI) prognostic index.

PubMed

Silverstein, Melvin J; Lagios, Michael D

2015-01-01

The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (DCIS) (tumor size, margin width, nuclear grade, age, and comedonecrosis). With five times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥3 mm. Excision plus RT achieves the less than 20% local recurrence threshold at 12 years for patients who score 7 and have margins <3 mm, patients who score 8 and have margins ≥3 mm, and for patients who score 9 and have margins ≥5 mm. Mastectomy is required for patients who score 8 and have margins <3 mm, who score 9 and have margins <5 mm and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. DCIS is a highly favorable disease. There is no difference in mortality rate regardless of which treatment is chosen. The USC/VNPI is a numeric tool that can be used to aid the treatment decision-making process. © 2015 Wiley Periodicals, Inc.

Meta-Analyses of ALDH2 and ADH1B with Alcohol Dependence in Asians

ERIC Educational Resources Information Center

Luczak, Susan E.; Glatt, Stephen J.; Wall, Tamara J.

2006-01-01

Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant [asterisk]2 allele was protective against alcohol dependence, and possession of a 2nd [asterisk]2 allele did not offer significant additional…

Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase.

PubMed Central

Burdette, D; Zeikus, J G

1994-01-01

The purification and characterization of three enzymes involved in ethanol formation from acetyl-CoA in Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E) is described. The secondary-alcohol dehydrogenase (2 degrees Adh) was determined to be a homotetramer of 40 kDa subunits (SDS/PAGE) with a molecular mass of 160 kDa. The 2 degrees Adh had a lower catalytic efficiency for the oxidation of 1 degree alcohols, including ethanol, than for the oxidation of secondary (2 degrees) alcohols or the reduction of ketones or aldehydes. This enzyme possesses a significant acetyl-CoA reductive thioesterase activity as determined by NADPH oxidation, thiol formation and ethanol production. The primary-alcohol dehydrogenase (1 degree Adh) was determined to be a homotetramer of 41.5 kDa (SDS/PAGE) subunits with a molecular mass of 170 kDa. The 1 degree Adh used both NAD(H) and NADP(H) and displayed higher catalytic efficiencies for NADP(+)-dependent ethanol oxidation and NADH-dependent acetaldehyde (identical to ethanal) reduction than for NADPH-dependent acetaldehyde reduction or NAD(+)-dependent ethanol oxidation. The NAD(H)-linked acetaldehyde dehydrogenase was a homotetramer (360 kDa) of identical subunits (100 kDa) that readily catalysed thioester cleavage and condensation. The 1 degree Adh was expressed at 5-20% of the level of the 2 degrees Adh throughout the growth cycle on glucose. The results suggest that the 2 degrees Adh primarily functions in ethanol production from acetyl-CoA and acetaldehyde, whereas the 1 degree Adh functions in ethanol consumption for nicotinamide-cofactor recycling. Images Figure 1 PMID:8068002

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli.

PubMed

Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-04-16

The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli

PubMed Central

Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-01-01

Background The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. Results We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Conclusion Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains. PMID:18412983

Co-expression of TAL1 and ADH1 in recombinant xylose-fermenting Saccharomyces cerevisiae improves ethanol production from lignocellulosic hydrolysates in the presence of furfural.

PubMed

Hasunuma, Tomohisa; Ismail, Ku Syahidah Ku; Nambu, Yumiko; Kondo, Akihiko

2014-02-01

Lignocellulosic biomass dedicated to bioethanol production usually contains pentoses and inhibitory compounds such as furfural that are not well tolerated by Saccharomyces cerevisiae. Thus, S. cerevisiae strains with the capability of utilizing both glucose and xylose in the presence of inhibitors such as furfural are very important in industrial ethanol production. Under the synergistic conditions of transaldolase (TAL) and alcohol dehydrogenase (ADH) overexpression, S. cerevisiae MT8-1X/TAL-ADH was able to produce 1.3-fold and 2.3-fold more ethanol in the presence of 70 mM furfural than a TAL-expressing strain and a control strain, respectively. We also tested the strains' ability by mimicking industrial ethanol production from hemicellulosic hydrolysate containing fermentation inhibitors, and ethanol production was further improved by 16% when using MT8-1X/TAL-ADH compared to the control strain. Transcript analysis further revealed that besides the pentose phosphate pathway genes TKL1 and TAL1, ADH7 was also upregulated in response to furfural stress, which resulted in higher ethanol production compared to the TAL-expressing strain. The improved capability of our modified strain was based on its capacity to more quickly reduce furfural in situ resulting in higher ethanol production. The co-expression of TAL/ADH genes is one crucial strategy to fully utilize undetoxified lignocellulosic hydrolysate, leading to cost-competitive ethanol production. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma

PubMed Central

Zhu, Sha; Ward, B. Marie; Yu, Jun; Matthew-Onabanjo, Asia N.; Janusis, Jenny; Hsieh, Chung-Cheng; Tomaszewicz, Keith; Hutchinson, Lloyd; Zhu, Lihua Julie; Kandil, Dina; Shaw, Leslie M.

2018-01-01

Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC. PMID:29669935

Relationships between immunophenotype, Ki-67 index, microvascular density, Ep-CAM/P-cadherin, and MMP-2 expression in early-stage invasive ductal breast cancer.

PubMed

Niemiec, Joanna A; Adamczyk, Agnieszka; Małecki, Krzysztof; Majchrzyk, Kaja; Ryś, Janusz

2012-12-01

There is still a lack of complete consensus on immunohistochemical surrogate markers for luminal A (LA) and luminal B (LB), HER2, and basal-like subtypes of breast carcinomas and their correlation with cancer cell adhesion and invasion-promoting factors. Therefore, early-stage invasive ductal breast cancer patients (N=209) were recruited to the study and divided into 4 subtypes, on the basis of the expression of the estrogen/progesterone receptor and HER2 (LA: 74.4% of cases; LB: 7.8%; HER2: 5.6%; and triple-negative phenotype: 12.2%). Regardless of the above-mentioned classification, we divided all carcinomas into 2 groups: carcinomas expressing at least 1 basal marker [cytokeratine (CK)5/6, CK5, vimentin, epidermal growth factor receptor, or aberrant CK8/18 expression-membranous or in <10% of cells] versus carcinomas negative for basal markers. Then we studied the relationships between the above subtypes (2 classifications) and (i) the expression of adhesion molecules (Ep-CAM, P-cadherin), (ii) matrix metalloproteinases (MMP)-2, (iii) the proliferation index (MIB-1 LI), and (iv) the microvascular density. We confirmed that triple-negative phenotypes are characterized by basal marker expression, a high tumor grade, and high MIB-1 LI. In this subtype, we found MMP-2 expression in stromal leukocytes less frequently. Both LA carcinomas and carcinomas negative for basal markers were more often negative for epithelial cell adhesion molecule (Ep-CAM) and P-cadherin. Moreover, we noted a higher mean value of microvascular density in CK5/6 and Ep-CAM-immunopositive tumors, carcinomas with aberrant CK8/18 expression, and carcinomas with no or strong expression of MMP-2 in stromal fibroblast-like cells. These results might suggest that mechanisms of stroma remodeling and carcinogenesis (Ep-CAM is the suggested marker of breast progenitors) may differ between breast cancer subtypes.

Benign Breast Disease Team Project — EDRN Public Portal

Cancer.gov

To identify women diagnosed with atypical ductal hyperplasia (ADH) who are at increased risk of developing invasive breast cancer (IBC) and who might benefit from risk reduction with the use of chemoprevention agents such as Tamoxifen. (Note: A companion protocol will study women with DCIS and their risk for invasive breast cancer.)

Effets du Parecoxib dans la Prévention des Adhérences abdominales postopératoires: étude expérimentale randomisée chez les rats

PubMed Central

Arung, Willy; Tshilombo, François; Odimba, Etienne

2015-01-01

Introduction Bien d’études ont été menées sur les adhérences intrapéritonéales, mais aucune unanimité n'est encore acquise sur leur prévention. Le but de notre étude a été d’évaluer le potentiel effet d'un antiinflammatoire, parecoxib dans la prévention des adhérences ainsi que sur la cicatrisation chez des rats. Méthodes Dans un modèle expérimental d'adhérences postopératoires secondaires à des lésions péritonéales par brûlure, 30 rats furent randomisés en trois groupes suivant le mode d'administration de parecoxib (groupe contrôle; intrapéritonéal; intramusculaire. Résultats Le parecoxib a significativement diminué la quantité (p < .05) et la sévérité (p < .01) des adhérences postopératoires dans les deux modèles expérimentaux. Au total, 21 rats ont développé des adhérences, respectivement 9 (100%) dans le groupe A, 5 (50%) dans le groupe B et 7 (70%) dans le groupe C (p = 0.05). Du point de vue de la formation des adhérences au site du traumatisme, dix-neuf rats en ont développé: 9 (100%) dans le groupe A et 5 (50%) pour chacun de deux autres groupes B et C. Une différence significative a été constatée en comparant ces groupes deux à deux: A vs B (p < 0.05); A vs C (p < 0,05). Parecoxib n'a pas compromis la cicatrisation intestinale, ni cutanée. Conclusion Cette étude a montré que le parecoxib pouvait réduire la formation des adhérences postopératoires. La confirmation de la sécurité du parecoxib sur les anastomoses intestinales doit être investiguée au cours d'autres expérimentations. PMID:26966478

Initial experience of automated breast volume scanning (ABVS) and ultrasound elastography in predicting breast cancer subtypes and staging.

PubMed

Wang, Xiao-Lei; Tao, Lin; Zhou, Xian-Li; Wei, Hong; Sun, Jia-Wei

2016-12-01

Breast cancer is a heterogeneous disease consisting of distinct histopathological subtypes with different clinical outcomes. In this article, we identified the automated breast volume scanning (ABVS) and shear wave velocity (SWV) characteristics of different pathological types of breast carcinoma. A retrospective review of both ABVS and SWV imaging of 118 consecutive breast masses was performed. The imaging features of both techniques were assessed with reference to histopathological results. Echo heterogeneity with a smooth and lobulated margin was a significant feature more frequently found in mucinous carcinoma groups (100%, P < 0.05). Between different stages of ductal carcinoma, echo homogeneity was more likely in high-grade ductal carcinomas (P < 0.05). SWV differences existed between inside tumor areas and either tumor boundary or tissues outside the tumors (P < 0.05), and values differed between different breast carcinoma stages. The central and tumor margin areas of ductal carcinomas were much harder than in tubular carcinoma and micro-carcinoma, respectively (P < 0.05). SWV ROC curve analyses yielded a cut-off value of 3.015 m/s between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma in the central part of lesions, with 83.5% sensitivity and 80% specificity for T0 vs T1-3 staging. Since some features were associated with different breast carcinoma types and stages, ABVS and SWV imaging has the potential to give clues about breast carcinoma differentiation in a non-invasive manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular-fibrosis and tumor progression

PubMed Central

Laklai, Hanane; Miroshnikova, Yekaterina A.; Pickup, Michael W.; Collisson, Eric A.; Kim, Grace E.; Barrett, Alex S.; Hill, Ryan C.; Lakins, Johnathon N.; Schlaepfer, David D.; Mouw, Janna K.; LeBleu, Valerie S.; Roy, Nilotpal; Novitskiy, Sergey V.; Johansen, Julia S.; Poli, Valeria; Kalluri, Raghu; Iacobuzio-Donahue, Christine A.; Wood, Laura D.; Hebrok, Matthias; Hansen, Kirk; Moses, Harold L.; Weaver, Valerie M.

2016-01-01

Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality yet anti-stromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor β (TGF-β) signaling have elevated epithelial Stat3 activity and develop a stiffer, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several Kras-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby Stat3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial Stat3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated Stat3 associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors, and highlight Stat3 and mechanics as key drivers of this phenotype. PMID:27089513

Imaging pancreatobiliary ductal system with optical coherence tomography: A review

PubMed Central

Mahmud, Mohammad S; May, Gray R; Kamal, Mohammad M; Khwaja, Ahmed S; Sun, Carry; Vitkin, Alex; Yang, Victor XD

2013-01-01

An accurate, noninvasive and cost-effective method of in situ tissue evaluation during endoscopy would be highly advantageous for the detection of dysplasia or early cancer and for identifying different disease stages. Optical coherence tomography (OCT) is a noninvasive, high-resolution (1-10 μm) emerging optical imaging method with potential for identifying microscopic subsurface features in the pancreatic and biliary ductal system. Tissue microstructure of pancreaticobiliary ductal system has been successfully imaged by inserting an OCT probe through a standard endoscope operative channel. High-resolution OCT images and the technique’s endoscopic compatibility have allowed for the microstructural diagnostic of the pancreatobiliary diseases. In this review, we discussed currently available pancreaticobiliary ductal imaging systems to assess the pancreatobiliary tissue microstructure and to evaluate varieties of pancreaticobiliary disorders and diseases. Results show that OCT can improve the quality of images of pancreatobiliary system during endoscopic retrograde cholangiopancheatography procedure, which may be important in distinguishing between the neoplastic and non-neoplastic lesions. PMID:24255746

Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis.

PubMed

Ishioka, Kuka; Masaoka, Hiroyuki; Ito, Hidemi; Oze, Isao; Ito, Seiji; Tajika, Masahiro; Shimizu, Yasuhiro; Niwa, Yasumasa; Nakamura, Shigeo; Matsuo, Keitaro

2018-04-03

Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (P interaction  = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.

Immunohistochemical status of p53, MDM2, bcl2, bax, and ER in invasive ductal breast carcinoma in Tunisian patients.

PubMed

Baccouche, Sami; Daoud, Jamel; Frikha, Mounir; Mokdad-Gargouri, Raja; Gargouri, Ali; Jlidi, Rachid

2003-12-01

TP53 gene alterations have been associated with sporadic breast cancer. To assess the role of p53 in invasive ductal carcinoma (IDC) of the breast among Tunisian patients, p53 protein status was studied by immuno-histochemical analysis. The p53 protein was expressed in 41 of 70 (58%) tumors. Study of the status of its target gene expression showed that MDM2 was overexpressed in 43 tumors (61%), bcl2 in 29 (41%), and bax in only 9 (12%). Estrogen receptor (ER) was detected in 38 tumor tissues (54%). The accumulated p53 was significantly associated with MDM2-positive, bcl2-negative, and ER-negative tumors (P = 0.024, P = 0.000027, and P = 0.000008, respectively), whereas with bax the correlaton was not significant. Bcl2 immunostaining displayed a positive correlation with ER (P = 0.001). A significantly higher fraction of p53-positive cells was observed in ER-negative SBRII-SBRIII tumors than in ER-positive SBRI-SBRII tumors (P = 0.000066). bcl2-positive tumors were significantly correlated with ER-positive/SBRI-SBRII tumors (P = 0.007), but negatively correlated with p53/bax (P = 0000004). MDM2 immunostaining displayed the same phenotype as p53 in the correlation with bcl2 and ER (P = 0.003), strengthened by significant associations between MDM2-positive/p53-positive and bcl2-negative or ER-negative, respectively (P = 0.00005 and P = 0.000001, respectively). MDM2-positive cells were significantly correlated with the p53-positive/bax-negative phenotype (P = 0.04). These results suggest that p53 accumulated in these tumor tissues is associated with bad prognostic markers (ER-negative, SBRIII) of IDC. MDM2 overexpression might be responsible for the accumulated p53 value in IDC. Regulation of the apoptotic process is involved in IDC; bcl2 is associated with a good prognostic marker (ER-positive and SBRI-II), whereas the regulation of bax is complex and does not necessarily correlate with the overexpression of p53.

Effects of large pressure amplitude low frequency noise in the parotid gland perivasculo-ductal connective tissue.

PubMed

Oliveira, Pedro; Brito, José; Mendes, João; da Fonseca, Jorge; Águas, Artur; Martins dos Santos, José

2013-01-01

In tissues and organs exposed to large pressure amplitude low frequency noise fibrosis occurs in the absence of inflammatory signs, which is thought to be a protective response. In the parotid gland the perivasculo-ductal connective tissue surrounds arteries, veins and the ductal tree. Perivasculo-ductal connective tissue is believed to function as a mechanical stabilizer of the glandular tissue. In order to quantify the proliferation of perivasculo-ductal connective tissue in large pressure amplitude low frequency noise-exposed rats we used sixty Wistar rats which were equally divided into 6 groups. One group kept in silence, and the remaining five exposed to continuous large pressure amplitude low frequency noise: g1-168h (1 week); g2-504h (3 weeks); g3-840h (5 weeks); g4-1512h (9 weeks); and g5-2184h (13 weeks). After exposure, parotid glands were removed and the perivasculo-ductal connective tissue area was measured in all groups. We applied ANOVA statistical analysis, using SPSS 13.0. The global trend is an increase in the average perivasculo-ductal connective tissue areas, that develops linearly and significantly with large pressure amplitude low frequency noise exposure time (p < 0.001). It has been suggested that the biological response to large pressure amplitude low frequency noise exposure is associated with the need to maintain structural integrity. The structural reinforcement would be achieved by increased perivasculo-ductal connective tissue. Hence, these results show that in response to large pressure amplitude low frequency noise exposure, rat parotid glands increase their perivasculo-ductal connective tissue.

Persistence of hAQP1 expression in human salivary gland cells following AdhAQP1 transduction is associated with a lack of methylation of hCMV promoter

PubMed Central

Zheng, C; Baum, BJ; Liu, X; Goldsmith, CM; Perez, P; Jang, S-I; Cotrim, AP; McCullagh, L; Ambudkar, IS; Alevizos, I

2017-01-01

In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector encoding human aquaporin-1 (hAQP1). This vector uses the human cytomegalovirus enhancer/promoter (hCMVp). As subject peak responses were at times much longer (7–42 days) than expected, we hypothesized that the hCMVp may not be methylated in human salivary gland cells to the extent previously observed in rodent salivary gland cells. This hypothesis was supported in human salivary gland primary cultures and human salivary gland cell lines after transduction with AdhAQP1. Importantly, hAQP1 maintained its function in those cells. Conversely, when we transduced mouse and rat cell lines in vitro and submandibular glands in vivo with AdhAQP1, the hCMVp was gradually methylated over time and associated with decreased hAQP1 expression and function in vitro and decreased hAQP1 expression in vivo. These data suggest that the hCMVp in AdhAQP1was probably not methylated in transduced human salivary gland cells of responding subjects, resulting in an unexpectedly longer functional expression of hAQP1. PMID:26177970

Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model.

PubMed Central

Pour, P. M.; Kazakoff, K.

1996-01-01

Previous studies have shown that some N-nitrosobis (2-oxopropyl)amine (BOP)-induced ductal/ductular pancreatic cancers in the hamster model develop within islets and that streptozotocin (SZ) pretreatment that caused islet degeneration and atrophy inhibits pancreatic cancer induction. Hence, it appears that in this model islets play a significant role in exocrine pancreatic carcinogenesis. To examine whether stimulation of islet cell proliferation (nesidioblastosis) enhances pancreatic exocrine cancer development, we tested the effect of the pancreatic carcinogen BOP in hamsters after induction of nesidioblastosis by cellophane wrapping. Before wrapping, hamsters were treated with SZ to inhibit pancreatic tumor induction in the unwrapped pancreatic tissues. Control groups with a wrapped pancreas did not receive SZ. Six weeks after SZ treatment, all hamsters were treated with BOP (10 mg/kg body weight) weekly for 10 weeks and the experiment was terminated 38 weeks after the last BOP treatment. Many animals recovered from their diabetes at the time when BOP was injected and many more after BOP treatment. Only nine hamsters remained diabetic until the end of the experiment. Both SZ-treated and control groups developed proliferative and malignant pancreatic ductal-type lesions primarily in the wrapped area (47%) but less frequently in the larger segments of the pancreas, including the splenic lobe (34%), gastric lobe (13%), and duodenal lobe (6%). Only a few lesions developed in the unwrapped pancreatic region of nine diabetic hamsters with atrophic islets, whereas seven of these hamsters had tumors in the wrapped area. Histologically, most tumors appeared to originate from islets, many invasive carcinomas had foci of islets, and some tumor cells showed reactivity with anti-insulin. The results show that, in the BOP hamster model, islets are the site of formation of the major fraction of exocrine pancreatic cancer and that induction of nesidioblastosis enhances

Overexpression of ADH1 and HXT1 genes in the yeast Saccharomyces cerevisiae improves the fermentative efficiency during tequila elaboration.

PubMed

Gutiérrez-Lomelí, Melesio; Torres-Guzmán, Juan Carlos; González-Hernández, Gloria Angélica; Cira-Chávez, Luis Alberto; Pelayo-Ortiz, Carlos; Ramírez-Córdova, Jose de Jesús

2008-05-01

This work assessed the effect of the overexpression of ADH1 and HXT1 genes in the Saccharomyces cerevisiae AR5 strain during fermentation of Agave tequilana Weber blue variety must. Both genes were cloned individually and simultaneously into a yeast centromere plasmid. Two transformant strains overexpressing ADH1 and HXT1 individually and one strain overexpressing both genes were randomly selected and named A1, A3 and A5 respectively. Overexpression effect on growth and ethanol production of the A1, A3 and A5 strains was evaluated in fermentative conditions in A. tequilana Weber blue variety must and YPD medium. During growth in YPD and Agave media, all the recombinant strains showed lower cell mass formation than the wild type AR5 strain. Adh enzymatic activity in the recombinant strains A1 and A5 cultivated in A. tequilana and YPD medium was higher than in the wild type. The overexpression of both genes individually and simultaneously had no significant effect on ethanol formation; however, the fermentative efficiency of the A5 strain increased from 80.33% to 84.57% and 89.40% to 94.29% in YPD and Agave medium respectively.

Metastatic carcinoma of breast or a chordoma? A case report and clinical perspectives.

PubMed

Trivedi, Sachin; Odrazka, Karel

2015-01-01

We present a case of chordoma in a patient who had been previously treated for ductal carcinoma of the breast. The initial clinical findings and radiological studies suggested a possibility of metastases. However, the findings also adhered to the classical presentations and findings of the chordoma of the base of skull. It was only after the surgical resection and immunohistochemical confirmation that the diagnosis of chordoma could be established. Here, we discuss chordoma with the analysis of our clinical intrigue.

Factors associated with the increasing trend of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ: Analysis of Surveillance, Epidemiology, and End Results data.

PubMed

You, Qiuting; Chen, Kai; Li, Yudong; Lai, Jianguo; Fang, Yichao; Shen, Shiyu; Liu, Yicheng; Su, Fengxi; Yu, Fengyan

2018-05-22

Our study aimed to investigate the factors influencing trends of contralateral prophylactic mastectomy (CPM) among patients with unilateral ductal carcinoma in situ (DCIS). We used the Surveillance, Epidemiology, and End Results (SEER) data to identify patients with unilateral DCIS diagnosed from 1998 to 2013. Patients were categorized as breast-conserving surgery (BCS), Unilateral Mastectomy and CPM group. Univariate and multivariate logistic regressions were applied to assess the factors associated with undergoing CPM among mastectomy patients. The trends of CPM among mastectomy patients through year were presented by different subgroups of sociodemographic and pathological characteristics. Of those, 105326 patients with DCIS were identified, and 6370 patients underwent CPM. The proportion of CPM was 6.05% for all surgically-treated patients and 21.09% for mastectomy patients, and it increased more than six-fold between 1998 and 2013 (from 1.74% to 10.89% for all surgically-treated patients and from 5.44% to 37.47% for mastectomy patients). Younger age, white race, married status, smaller tumor size, positive ER and PR status were significantly associated with higher CPM proportion among mastectomy patients. The proportion of CPM was increasing through year, and the increasing trends were obvious in the subgroups of younger, white, married, metropolitan, with higher bachelor degree and higher median family income patients, while there were no apparent differences in the trends between subgroups of pathological characteristics. The trends of CPM among mastectomy patients were increasing through years and influenced by patients' sociodemographic characteristics, but not pathological characteristics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

PubMed Central

Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

2016-01-01

In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

PubMed

Schuh, Fernando; Biazús, Jorge Villanova; Resetkova, Erika; Benfica, Camila Zanella; Ventura, Alessandra de Freitas; Uchoa, Diego; Graudenz, Márcia; Edelweiss, Maria Isabel Albano

2015-07-10

Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic

Flat epithelial atypia of the breast.

PubMed

Lerwill, Melinda F

2008-04-01

Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a "flat" pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.

Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome.

PubMed

Joshi, M G; Lee, A K; Loda, M; Camus, M G; Pedersen, C; Heatley, G J; Hughes, K S

1996-02-01

Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome. Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival. Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival. Male breast carcinoma presents in an advanced stage with less favorable

The joint effects of ADH1B variants and childhood adversity on alcohol related phenotypes in African-American and European-American women and men.

PubMed

Sartor, Carolyn E; Wang, Zuoheng; Xu, Ke; Kranzler, Henry R; Gelernter, Joel

2014-12-01

The ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes. This study examined the joint effects of variation in ADH1B and childhood adversity-a well-documented risk factor for alcohol problems and moderator of genetic liability to psychiatric outcomes-on maximum drinks consumed in a 24-hour period (maxdrinks) and alcohol use disorder (AUD) symptoms. Data were drawn from 2,617 African-American (AA) and 1,436 European-American (EA) participants (42% female) in a multisite genetic study of substance dependence. We tested the most significant ADH1B single nucleotide polymorphisms for alcohol dependence from a genomewide association study with this sample, ADH1B-rs1229984 (Arg48His) and ADH1B-rs2066702 (Arg370Cys), in EA and AA subsamples, respectively. Ordinal regression analyses conducted separately by sex and population revealed significant main effects for childhood adversity for both alcohol phenotypes in AA women and men and for maxdrinks in EA women. A significant rs1229984 by childhood adversity interaction was observed for AUD symptoms in EA men. Unexposed His-allele carriers reported a mean of 3.6 AUD criteria, but adversity-exposed His-allele carriers endorsed approximately the same number (6.3) as those without the protective allele (6.3 and 7.0 for adversity-exposed and -unexposed groups, respectively). Results suggest that under conditions of childhood adversity, the His allele does not exert its protective effects in EA men (OR = 0.57, CI: 0.32 to 1.01; p = 0.056). Findings highlight the robust risk effect conferred by childhood adversity and the importance of considering population and sex in genetically informative investigations of its association with alcohol outcomes. Copyright © 2014 by the Research Society on Alcoholism.

Trends in gastrectomy and ADH1B and ALDH2 genotypes in Japanese alcoholic men and their gene-gastrectomy, gene-gene and gene-age interactions for risk of alcoholism.

PubMed

Yokoyama, Akira; Yokoyama, Tetsuji; Matsui, Toshifumi; Mizukami, Takeshi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

2013-01-01

The life-time drinking profiles of Japanese alcoholics have shown that gastrectomy increases susceptibility to alcoholism. We investigated the trends in gastrectomy and alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genotypes and their interactions in alcoholics. This survey was conducted on 4879 Japanese alcoholic men 40 years of age or older who underwent routine gastrointestinal endoscopic screening during the period 1996-2010. ADH1B/ALDH2 genotyping was performed in 3702 patients. A history of gastrectomy was found in 508 (10.4%) patients. The reason for the gastrectomy was peptic ulcer in 317 patients and gastric cancer in 187 patients. The frequency of gastrectomy had gradually decreased from 13.3% in 1996-2000 to 10.5% in 2001-2005 and to 7.8% in 2006-2010 (P < 0.0001). ADH1B*1/*1 was less frequent in the gastrectomy group than in the non-gastrectomy group (age-adjusted prevalence: 20.4 vs. 27.6%, P = 0.006). ALDH2 genotype distribution did not differ between the two groups. The frequency of inactive ALDH2*1/*2 heterozygotes increased slightly from 13.0% in 1996-2000 to 14.0% in 2001-2005 and to 15.4% in 2006-2010 (P < 0.08). Two alcoholism-susceptibility genotypes, ADH1B*1/*1 and ALDH2*1/*1, modestly but significantly tended not to occur in the same individual (P = 0.026). The frequency of ADH1B*1/*1 decreased with ascending age groups. The high frequency of history of gastrectomy suggested that gastrectomy is still a risk factor for alcoholism, although the percentage decreased during the period. The alcoholism-susceptibility genotype ADH1B*1/*1 was less frequent in the gastrectomy group, suggesting a competitive gene-gastrectomy interaction for alcoholism. A gene-gene interaction and gene-age interactions regarding the ADH1B genotype were observed.

Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

PubMed

Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

2018-06-01

To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool

PubMed Central

dos-Santos, Petra B; Zanetti, Juliana S; Vieira-de-Mello, Gabriela S; Rêgo, Moacyr BM; A, Alfredo Ribeiro-Silva; Beltrão, Eduardo Isidoro Carneiro

2014-01-01

Increased sialylation and β1,6-branched oligosaccharides has been associated with a variety of structural changes in cell surface carbohydrates, most notably in tumorigenesis. Lectins are defined as proteins that preferentially recognize and bind carbohydrate complexes protruding from glycolipids and glycoproteins. This interaction with carbohydrates can be as specific as the interaction between antigen and antibody. Due to this type of interaction lectins have been used as experimental auxiliary tools in histopathological diagnosis of cancer. This study was designed to evaluate the differential expression of sialic acids and β1,6-N-acetylglucosaminyltransferase V (MGAT5) in invasive (IDC) and in situ (DCIS) ductal carcinoma of the breast and its possible application as prognostic biomarkers. A possible transition between pre-malign and malign lesions was evaluated using DCIS samples. Biopsies were analyzed regarding the expression of MUC1, p53, Ki-67, estrogen receptor, progesterone receptor, HER-2 and MGAT5. α2,6-linked sialic acids residues recognized by SNA lectin was overexpressed in 33.3% of IDC samples and it was related with Ki-67 (p=0.042), PR (p=0.029), lymphnodes status (p=0.017) and death (p=0.011). Regarding survival analysis SNA was the only lectin able to correlate with specific-disease survival and disease-free survival (p=0.024 and p=0.041, respectively), besides, it presents itself as an independent variable by Cox Regression analysis (p= 0.004). Comparing IDC and DCIS cases, only SNA showed different staining pattern (p=0.034). The presence of sialic acids on tumor cell surface can be an indicative of poor prognosis and our study provides further evidence that SNA lectin can be used as a prognostic probe in IDC and DCIS patients. PMID:24966944

Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma.

PubMed

Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Marike Boezen, H; de Bock, Geertruida H; van der Graaf, Winette T A; Wesseling, Jelle

2011-10-01

The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.

Informed shared decision-making supported by decision coaches for women with ductal carcinoma in situ: study protocol for a cluster randomized controlled trial.

PubMed

Berger-Höger, Birte; Liethmann, Katrin; Mühlhauser, Ingrid; Haastert, Burkhard; Steckelberg, Anke

2015-10-12

Women with breast cancer want to participate in treatment decision-making. Guidelines have confirmed the right of informed shared decision-making. However, previous research has shown that the implementation of informed shared decision-making is suboptimal for reasons of limited resources of physicians, power imbalances between patients and physicians and missing evidence-based patient information. We developed an informed shared decision-making program for women with primary ductal carcinoma in situ (DCIS). The program provides decision coaching for women by specialized nurses and aims at supporting involvement in decision-making and informed choices. In this trial, the informed shared decision-making program will be evaluated in breast care centers. A cluster randomized controlled trial will be conducted to compare the informed shared decision-making program with standard care. The program comprises an evidence-based patient decision aid and training of physicians (2 hours) and specialized breast care and oncology nurses (4 days) in informed shared decision-making. Sixteen certified breast care centers will be included, with 192 women with primary DCIS being recruited. Primary outcome is the extent of patients' involvement in shared decision-making as assessed by the MAPPIN-Odyad (Multifocal approach to the 'sharing' in shared decision-making: observer instrument dyad). Secondary endpoints include the sub-measures of the MAPPIN-inventory (MAPPIN-Onurse, MAPPIN-Ophysician, MAPPIN-Opatient, MAPPIN-Qnurse, MAPPIN-Qpatient and MAPPIN-Qphysician), informed choice, decisional conflict and the duration of encounters. It is expected that decision coaching and the provision of evidence-based patient decision aids will increase patients' involvement in decision-making with informed choices and reduce decisional conflicts and duration of physician encounters. Furthermore, an accompanying process evaluation will be conducted. To our knowledge, this is the first study

Trends in Detection of Invasive Cancer and Ductal Carcinoma In Situ at Biennial Screening Mammography in Spain: A Retrospective Cohort Study

PubMed Central

Román, Marta; Rué, Montse; Sala, Maria; Ascunce, Nieves; Baré, Marisa; Baroja, Araceli; De la Vega, Mariola; Galcerán, Jaume; Natal, Carmen; Salas, Dolores; Sánchez-Jacob, Mercedes; Zubizarreta, Raquel; Castells, Xavier

2013-01-01

Background Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods Retrospective cohort study of 1,564,080 women aged 45–69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002. PMID:24376649

Prognostic Significance of Clinicopathologic Features in Patients With Breast Ductal Carcinoma-in-Situ Who Received Breast-Conserving Surgery.

PubMed

Kuo, Sung-Hsin; Lo, Chiao; Chen, Yu-Hsuan; Lien, Huang-Chun; Kuo, Wen-Hung; Wang, Ming-Yang; Lee, Yi-Hsuan; Huang, Chiun-Sheng

2018-04-10

To identify whether a certain group of breast ductal carcinoma-in-situ (DCIS) patients can be treated with breast-conserving surgery (BCS) alone; to analyze the clinicopathologic features of DCIS and tamoxifen administration in patients treated with BCS who developed ipsilateral breast tumor recurrence (IBTR). Data for 375 women with breast DCIS who underwent BCS at our institute between June 2003 and October 2010 were analyzed. The patients were divided into different categories according to the recurrence risk predicted using the California/Van Nuys Prognostic Index (USC/VNPI) score (4-6, 7-9, and 10-12), Eastern Cooperative Oncology Group (ECOG) E5194 criteria, or combined risk features with USC/VNPI score and ECOG E5194 criteria. The IBTR and disease-free survival (DFS) rates were calculated by the Kaplan-Meier method. The prognostic effects of age, tumor size, tumor grade, margin width, estrogen receptor status, USC/VNPI score, low-risk characteristics, and tamoxifen use were evaluated by log-rank tests. Of the patients, 168 were treated with breast irradiation after BCS and 207 were not. The patients who were treated with radiotherapy (RT) tended to be younger (< 40 years), to have higher USC/VNPI scores (7-9), and to meet the ECOG E5194 non-cohort 1 criteria. The 7-year risk of IBTR was 6.2% (n = 11) in the patients who received irradiation and 9.0% (n = 22) in those who did not. DFS rates were better in the patients who underwent RT than in those who did not (93.3% vs. 88.5%, P = .056). Among the patients who underwent BCS alone, age ≥ 40 years, margin width > 10 mm, USC/VNPI scores 4-6, ECOG E5194 cohort 1 criteria, estrogen receptor-positive status, and tamoxifen use predicted lower IBTR and better DFS rates. In the multivariate analysis, combined low-risk characteristics (USC/VNPI scores 4-6 and meeting the ECOG E5194 cohort 1 criteria) were identified as an independent prognostic factor of lower IBTR (P = .028) and better DFS (P = .005). RT

The role of chalcones: helichrysetin, xanthohumol, and flavokawin-C in promoting neurite outgrowth in PC12 Adh cells.

PubMed

Phan, Chia-Wei; Sabaratnam, Vikineswary; Yong, Wai-Kuan; Abd Malek, Sri Nurestri

2018-05-01

Chalcones are a group of compounds widely distributed in plant kingdom. The aim of this study was to assess the neurite outgrowth stimulatory activity of selected chalcones, namely helichrysetin, xanthohumol and flavokawin-C. Using adherent rat pheochromocytoma (PC12 Adh) cells, the chalcones were subjected to neurite outgrowth assay and the extracellular nerve growth factor (NGF) levels were determined. Xanthohumol (10 μg/mL) displayed the highest (p < 0.05) percentage of neurite-bearing PC12 Adh cells and the highest (p < 0.05) NGF level in the culture medium of xanthohumol-treated cells. While, helichrysetin induced a moderately high numbers of neurite-bearing cells, flavokawin-C did not stimulate neurite outgrowth. This work supports the potential use of xanthohumol as a potential neuroactive compound to stimulate neurite outgrowth.

Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

PubMed

Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

2018-06-01

The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

Morphology of male breast carcinoma in the evaluation of prognosis.

PubMed

Cunha, F; André, S; Soares, J

1990-12-01

We studied a series of 44 consecutive cases of male breast carcinoma over a 14 year period in order to evaluate the clinico-pathological characteristics and the impact of some morphologic factors on prognosis. The age of the patients ranged from 38 to 84 years (mean 62 +/- 10.8). All the patients presented a painless mass, associated with nipple retraction in 13 cases (29.4%), skin ulceration in 12 cases (27.2%) and nipple discharge in 6 (13.6%). Microscopically all the tumors were infiltrating ductal carcinomas, 42 being of the NOS type. A better survival was associated with low mitotic index, T 1 tumors and absence of peritumoral lymphatic permeation. However, only these two parameters had statistical significance and were found to have predictive value on the prognosis of the disease. The degree of differentiation assessed according to Bloom and Richardson's classification showed no influence on prognosis. Post surgical radiotherapy did not seem to influence the outcome of the disease.

Quality of life in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative irradiation.

PubMed

Amichetti, M; Caffo, O; Arcicasa, M; Roncadin, M; Lora, O; Rigon, A; Zini, G; Armaroli, L; Coghetto, F; Zorat, P; Neri, S; Teodorani, N

1999-03-01

To evaluate the quality of life (QL) in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative irradiation. A self-completed questionnaire covering many disease-, symptom-, and treatment-specific issues was administered to 106 conservatively treated patients affected by non-infiltrating breast cancer. The questionnaire was based on a series of 34 items assessing five main fields of post-treatment adjustment: physical well being, sexual adaptation, aesthetic outcome, emotional/psychological well being, relational behaviour. Furthermore, the patients were requested to evaluate the degree of information provided by the medical staff concerning surgical procedures and radiation therapy, and to evaluate the effects of the treatment on their social and overall life. The questionnaire was completed by 83 patients (78%), who had a median follow-up of 54.5 months. This final sample had a median age of 50 years (range 29-88) at the time of treatment and 54 years (range 32-94) at the time of study. The patients claimed to be in good physical condition. Data relating to sexual life were provided by 93% of the sample. Some limitations in sexuality, some interference with sexual desire, and some modifications during intercourse were reported by 5, 6, and 5 patients, respectively. The subjective evaluations of the cosmetic results of the therapies were generally good. Only 13 patients (16%) reported the perception of a worsened body image. Forty-six percent of the sample (38 patients) declared that they felt tense, 48% (39 patients) nervous, 29% (38 patients) lonely, 59% (41 patients) anxious, and 41% (34 patients) depressed. Only seven patients (8%) declared that the treatment had had a bad effect on their social life, and 15 (18%) thought that their current life had been affected by the treatment. The amount of information received concerning the disease and treatment (surgery and radiotherapy) was considered sufficient by 79

Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways.

PubMed

Farnie, Gillian; Clarke, Robert B; Spence, Katherine; Pinnock, Natasha; Brennan, Keith; Anderson, Neil G; Bundred, Nigel J

2007-04-18

The epidermal growth factor receptor (EGFR) and Notch signaling pathways have been implicated in self-renewal of normal breast stem cells. We investigated the involvement of these signaling pathways in ductal carcinoma in situ (DCIS) of the breast. Samples of normal breast tissue (n = 15), pure DCIS tissue of varying grades (n = 35), and DCIS tissue surrounding an invasive cancer (n = 7) were used for nonadherent (i.e., mammosphere) culture. Mammosphere cultures were treated at day 0 with gefitinib (an EGFR inhibitor), DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester) (a gamma-secretase inhibitor), or Notch 4-neutralizing antibody. Mammosphere-forming efficiency (MFE) was calculated by dividing the number of mammospheres of 60 microm or more formed by the number of single cells seeded and is expressed as a percentage. The Notch 1 intracellular domain (NICD) was detected immunohistochemically in paraffin-embedded DCIS tissue from 50 patients with at least 60 months of follow-up. All statistical tests were two-sided. DCIS had a greater MFE than normal breast tissue (1.5% versus 0.5%, difference = 1%, 95% confidence interval [CI] = 0.62% to 1.25%, P<.001). High-grade DCIS had a greater MFE than low-grade DCIS (1.6% versus 1.09%, difference = 0.51%, 95% CI = 0.07% to 0.94%, P = .01). The MFE of high-grade DCIS treated with gefitinib in the absence of exogenous EGF was lower than that of high-grade DCIS treated with mammosphere medium lacking gefitinib and exogenous EGF (0.56% versus 1.36%, difference 0.8%, 95% CI = 0.33% to 1.4%, P = .004). Increased Notch signaling as detected by NICD staining was associated with recurrence at 5 years (P = .012). DCIS MFE was reduced when Notch signaling was inhibited using either DAPT (0.89% versus 0.51%, difference = 0.38%, 95% CI = 0.2% to 0.6%, P<.001) or a Notch 4-neutralizing antibody (0.97% versus 0.2%, difference = 0.77%, 95% CI = 0.52% to 1.0%, P<.001). We describe a novel primary culture technique

Molecular Variation of Adh and P6 Genes in an African Population of Drosophila Melanogaster and Its Relation to Chromosomal Inversions

PubMed Central

Benassi, V.; Aulard, S.; Mazeau, S.; Veuille, M.

1993-01-01

Four-cutter molecular polymorphism of Adh and P6, and chromosome inversion polymorphism of chromosome II were investigated in 95 isogenic lines of an Ivory Coast population of Drosophila melanogaster, a species assumed to have recently spread throughout the world from a West African origin. The P6 gene showed little linkage disequilibrium with the In(2L)t inversion, although it is located within this inversion. This suggests that the inversion and the P6 locus have extensively exchanged genetic information through either double crossover or gene conversion. Allozymic variation in ADH was in linkage disequilibrium with In(2L)t and In(2R)NS inversions. Evidence suggests either that inversion linkage with the Fast allele is selectively maintained, or that this allele only recently appeared. Molecular polymorphism at the Adh locus in the Ivory Coast is not higher than in North American populations. New haplotypes specific to the African population were found, some of them connect the ``Wa(s)-like'' haplotypes found at high frequencies in the United States to the other slow haplotypes. Their relation with In(2L)t supports the hypothesis that Wa(s) recently recombined away from an In(2L)t chromosome which may be the cause of its divergence from the other haplotypes. PMID:8349110

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases

PubMed Central

Lv, Zhuangwei; Liu, Min; Shen, Jinghui; Xiang, Dong; Ma, Yunfeng; Ji, Yanhong

2018-01-01

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER− and PR−. Furthermore, high serum levels of TGF-α were associated with HER2+ tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment. PMID:29904427

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases.

PubMed

Lv, Zhuangwei; Liu, Min; Shen, Jinghui; Xiang, Dong; Ma, Yunfeng; Ji, Yanhong

2018-06-01

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER - and PR - . Furthermore, high serum levels of TGF-α were associated with HER2 + tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment.

Quality of Life Over Time in Women Diagnosed with Ductal Carcinoma In situ, Early-Stage Invasive Breast Cancer, and Age-Matched Controls

PubMed Central

Jeffe, DB; Pérez, M; Liu, Y; Collins, KK; Aft, RL; Schootman, M

2012-01-01

Little is known about quality-of-life (QOL) differences over time between incident ductal carcinoma in situ (DCIS) and early-stage invasive breast cancer (EIBC) cases as compared with same-aged women without breast cancer (controls). We prospectively recruited and interviewed 1096 women (16.8% DCIS, 33.3% EIBC [25.7% Stage I, 7.6% Stage IIA], 49.9% controls; mean age 58; 23.7% non-white) a mean 6.7 weeks (T1), and 6.2 (T2), 12.3 (T3), and 24.4 months (T4) after surgery (patients) or screening mammogram (controls). We tested two hypotheses: (1) DCIS patients would report lower levels of QOL compared with controls but would report similar QOL compared with EIBC patients at baseline; and (2) DCIS patients’ QOL would improve during 2-year follow-up and approach levels similar to that of controls faster than EIBC patients. We tested Hypothesis 1 using separate general linear regression models for each of the eight subscales on the RAND 36-item Health Survey, controlling for variables associated with at least one subscale at T1. Both DCIS and EIBC patients reported lower QOL at T1 than controls on all subscales (each p < .05). We tested Hypothesis 2 using generalized estimating equations to examine change in each QOL subscale over time across the three diagnostic groups adjusting for covariates. By T3, physical functioning, role limitations due to physical problems, energy/fatigue, and general health each differed significantly by diagnostic group at P < 0.05, due to larger differences between EIBC patients and controls; but DCIS patients no longer differed significantly from controls on any of the QOL subscales. At T4, EIBC patients still reported worse physical functioning (P = 0.0001) and general health (P = 0.0017) than controls, possibly due to lingering treatment effects. DCIS patients’ QOL was similar to that of controls two years after diagnosis, but some aspects of EIBC patients’ QOL remained lower. PMID:22484800

Fatty acid synthase affects expression of ErbB receptors in epithelial to mesenchymal transition of breast cancer cells and invasive ductal carcinoma

PubMed Central

Chen, Tingting; Zhou, Lan; Li, Hua; Tian, Yuan; Li, Junqin; Dong, Lihua; Zhao, Yuhua; Wei, Dapeng

2017-01-01

The aim of the present study was to investigate changes in the expression of ErbBs during epithelial-mesenchymal transition (EMT) of breast cancer cells and its association with the expression of fatty acid synthase (FASN). MCF-7-MEK5 cells were used as the experimental model, while MCF-7 cells were used as a control. Tumor cells were implanted into nude mice for in vivo analysis. Cerulenin was used as a FASN inhibitor. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect expression levels of FASN and ErbB1-4. Immunohistochemistry was used to detect the expression of FASN and ErbB1-4 in 58 invasive ductal carcinomas (IDC), as well as their association with clinicopathological characteristics. The expression of FASN and ErbB1-4 in MCF-7-MEK5 cells and tumor tissues increased significantly compared with controls (P<0.001). Inhibition of FASN by cerulenin resulted in a significant decrease in expression of ErbB1, 2 and 4 (P<0.001), whereas there was no evident change in ErbB3. In IDC samples, the expression of FASN and ErbB1-4 increased considerably in lymph node metastases compared with non-lymph node metastases (P<0.05). ErbB2 expression increased in advanced clinical stages (II, III and IV) of IDC and in tumors with larger diameters (P<0.05). The expression of ErbB3 increased in ER-positive tumors (P<0.05). Additionally, a positive association between the expression of FASN and ErbB1, 2 and 4 was observed (P<0.05). FASN activates ErbB1, 2 and 4, and their dimers, which are polymerized via the microstructural domain of the cell membrane. This may initiate EMT and consequentlyincrease the invasion and migration of cancer cells. However, ErbB3 may also affect tumor progression via a FASN-independent pathway. PMID:29113229

How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey

PubMed Central

McCaffery, Kirsten; Nickel, Brooke; Moynihan, Ray; Hersch, Jolyn; Teixeira-Pinto, Armando; Irwig, Les; Barratt, Alexandra

2015-01-01

Objective There have been calls to remove ‘carcinoma’ from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as ‘abnormal cells’ versus ‘pre-invasive breast cancer cells’ on women's concern and treatment preferences. Setting and participants Community sample of Australian women (n=269) who spoke English as their main language at home. Design Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either ‘abnormal cells’ (arm A) or ‘pre-invasive breast cancer cells’ (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Results Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A (‘abnormal cells’ first term) indicated they would feel more concerned if given the alternative term (‘pre-invasive breast cancer cells’) compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from ‘abnormal cells’ to ‘pre-invasive breast cancer cells’ compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). Conclusions In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted women's concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards

A Duodenal Ulcer Caused by Pancreatic Ductal Hypertension with Chronic Pancreatitis.

PubMed

Imoto, Akira; Masuda, Daisuke; Okuda, Atsushi; Takagi, Wataru; Onda, Saori; Sano, Tatsushi; Mikami, Takashi; Mohamed, Malak; Ogura, Takeshi; Higuchi, Kazuhide

2015-01-01

We herein describe the case of a 67-year-old woman with a duodenal ulcer thought to be caused by elevated pancreatic ductal pressure. The patient complained of continuous upper abdominal pain. Her medical history included idiopathic chronic pancreatitis. Endoscopy revealed a huge duodenal ulcer located on the inferior duodenal angle, which had not been seen on endoscopic retrograde pancreatography two months previously. A combination study using endoscopy and contrast imaging confirmed the relationship between the duodenal ulcer and the pancreatic branch duct. To our knowledge, this is the first case of duodenal ulcer thought to be caused by elevated pancreatic ductal pressure.

ZEB1 expression is correlated with tumor metastasis and reduced prognosis of breast carcinoma in Asian patients.

PubMed

Xiang, Shuai; Liu, Ya-Min; Chen, Xu; Wang, Ya-Wen; Ma, Ran-Ran; Wu, Xiao-Juan; Gao, Peng

2015-07-01

Tumor metastasis is one of the key events leading to tumor relapse and poor prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated in human carcinogenesis. However, involvement of ZEB1 deregulation in tumorigenesis in Asian patients with breast carcinoma remains elusive. The present study included 102 Asian patients with breast carcinoma treated by surgery from January of 2005 to December of 2006, and the expression of ZEB1 was evaluated by immunohistochemistry. To further assess the prognostic value of ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of ZEB1 expression was found in carcinomas with higher aggressive potential. We also correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in invasive ductal carcinoma. Furthermore, our data suggested an elevated level of Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced overall survival and disease-free survival were observed in cases with positive ZEB1 expression than that in negative cases. Our results correlated ZEB1 with aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as a prognostic marker in breast carcinoma.

Association Between Hospital Financial Distress and Immediate Breast Reconstruction Surgery After Mastectomy Among Women With Ductal Carcinoma In Situ.

PubMed

Richards, Catherine A; Rundle, Andrew G; Wright, Jason D; Hershman, Dawn L

2018-04-01

Hospital financial distress (HFD) is a state in which a hospital is at risk of closure because of its financial condition. Hospital financial distress may reduce the services a hospital can offer, particularly unprofitable ones. Few studies have assessed the association of HFD with quality of care. To examine the association between HFD and receipt of immediate breast reconstruction surgery after mastectomy among women diagnosed with ductal carcinoma in situ (DCIS). This retrospective cohort study assessed data from the Nationwide Inpatient Sample of 5760 women older than 18 years (mean [SD] age: 57.5 [13.2]) with DCIS who underwent mastectomy in 2008-2012 at hospitals categorized by financial distress. Women treated at 1156 hospitals located in 538 different counties across Arkansas, Arizona, California, Colorado, Connecticut, Florida, Iowa, Kentucky, Massachusetts, Maryland, Missouri, North Carolina, New Hampshire, New Jersey, Nevada, New York, Oregon, Pennsylvania, Rhode Island, Utah, Virginia, Vermont, Washington, Wisconsin, West Virginia, and Wyoming were included. Of these, 2385 women (41.4%) underwent immediate breast reconstruction surgery. Women with invasive cancer were excluded. The database included unique hospital identification variables, and participants were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Data were analyzed from January 1, 2012, to February 28, 2014. The primary outcome was the adjusted association between HFD and receipt of immediate breast reconstruction surgery after mastectomy. In this analysis of database information, 2385 of 5760 women (41.4%) received immediate breast reconstruction surgery. Of these, 693 (36.7%) were treated at a hospital under high HFD and received immediate breast reconstruction surgery compared with 863 (44.0%) treated at a hospital under low HFD (P < .001). Reconstruction surgery was associated with younger age, white race, private insurance

Mineral exploration, Mahd adh Dhahab District, Kingdom of Saudi Arabia

USGS Publications Warehouse

Worl, Ronald G.

1978-01-01

Mahd adh Dhahab is the largest of numerous ancient gold mines scattered through the Precambrian shield of Saudi Arabia and the only one with recent production. During the period 1939-54, 765,768 fine ounces of gold and 1,002,029 ounces of silver were produced from the mines by the Saudi Arabian Mining Syndicate. Ore minerals at Mahd adh Dhahab include free gold and silver, tellurides, sphalerite, and chalcopyrite in and associated with a system of north-trending quartz veins and quartz veinlet stockworks. Pyrite is a common sulfide gangue mineral. Country rocks are a north dipping sequence of pyroclastic and transported pyroclastic rocks of the Hulayfah Group that are locally highly silicified and potassium-feldspathized. The prime target for this exploration program was a north-trending zone of quartz veins and breccias, faults, alteration, and metalization approximately 400 m wide and 1000 m long. The ancient and recent mine workings are located in the northern part of this zone. Although the quartz veins and alteration cut all lithologies, the major metalization is confined to the intersection of veins and agglomerate. Ten holes were diamond drilled to explore geochemical, geological, and geophysical targets in the area. A significant new zone of metalization was discovered 700 m south of the ancient and recent mine workings and within the same major zone of quartz veins, alteration, and faults. Metalization in this southern mineralized zone is at the intersection of the quartz veins and a distinctive and highly altered agglomerate. The total zone of vein and agglomerate intercept is potentially metalized and comprises a block of ground 40 m thick and 400 m wide along the strike of the agglomerate and projected downdip 250 m. Tonnage of this block is 17.2 million tons. The explored zone, approximately 25 percent of the potentially metalized rock, has a potential resource of 1.1 million tons containing 27 g/t gold and 73 g/t silver.

Heterogeneity of keratin expression and actin distribution in benign and malignant mammary diseases.

PubMed

Wada, T; Yasutomi, M; Yamada, K; Hashimura, K; Kunikata, M; Tanaka, T; Huang, J W; Mori, M

1991-01-01

Immunoreactivity of monoclonal anti-cytokeratin KL1, PKK1, K8.12 and anti-actin antibodies in 101 cases of diseased human breast lesions showed irregular keratin distribution in luminal cells of terminal ductal-lobular unit and basal layer cells of the interlobular and main duct. Actin staining was confined to myoepithelial cells. Benign lesions showed great heterogeneity in luminal cells of the terminal ductal-lobular units. Breast carcinoma showed a reduced staining for keratins, heterogeneity of keratin expression was found in solid tubular carcinoma, and actin was usually absent: however, papillo-ductal or comedo type had actin positive myoepithelial cells around carcinoma foci.

Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

PubMed

Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

2009-09-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

Targeted Overexpression of EZH2 in the Mammary Gland Disrupts Ductal Morphogenesis and Causes Epithelial Hyperplasia

PubMed Central

Li, Xin; Gonzalez, Maria E.; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D.; Kleer, Celina G.

2009-01-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with β-catenin, inducing β-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/β-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with β-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma. PMID:19661437

Ductal recanalization and stenting for late presenters with TGA intact ventricular septum

PubMed Central

Kothari, Shyam S; Ramakrishnan, Sivasubramanian; Senguttuvan, Nagendra Boopathy; Gupta, Saurabh Kumar; Bisoi, Akshay K

2011-01-01

Introduction: The ideal management strategy for patients presenting late with transposition of great arteries (TGA), intact ventricular septum (IVS), and regressed left ventricle (LV) is not clear. Primary switch, two-stage switch, and Senning operation are the options. Left ventricular retraining prior to arterial switch by ductal stenting may be effective, but the experience is very limited. Methods: Five of six children aged 3–6 months with TGA-IVS and regressed LV underwent recanalization and transcatheter stenting of ductus arteriosus. The ductal stent was removed during arterial switch surgery. Results: The procedure was successful in 5/6 patients. All the patients had totally occluded ductus and needed recanalization with coronary total occlusion hardware. The ductus was dilated and stented with coronary stents. In all the patients, there was significant luminal narrowing despite adequate stent placement and deployment. Two patients needed reintervention for abrupt closure of the stent. Ductal stenting resulted in left ventricular preparedness within 7–14 days. One patient died of progressive sepsis after 14 days of stenting, even though the LV was prepared. Four patients underwent successful uneventful arterial switch surgery. During surgery, it was observed that the mucosal folds of duct were protruding through the struts of the stent in one patient. Conclusions: Ductal stenting is a good alternative strategy for left ventricular retraining in TGA with regressed LV even in patients with occluded ducts. PMID:21976872

Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

ClinicalTrials.gov

2018-06-11

Ductal Breast Carcinoma In Situ; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma

Uroplakin II (UPII), GATA3, and p40 are Highly Sensitive Markers for the Differential Diagnosis of Invasive Urothelial Carcinoma.

PubMed

Hoang, Laura L; Tacha, David; Bremer, Ryan E; Haas, Thomas S; Cheng, Liang

2015-01-01

Distinguishing between invasive urothelial carcinoma from other genitourinary lesions such as prostatic and renal carcinomas can be difficult, and may require highly sensitive immunohistochemical markers. GATA-binding protein 3 (GATA3) has been reported in a high percentage of urothelial and breast carcinomas. Mouse monoclonal uroplakin II (UPII) and p40 antibodies have recently been developed and demonstrated high specificity in urothelial carcinoma. This study evaluated the immunohistochemical staining sensitivities of UPII, GATA3, p40, and p63 in the detection of invasive urothelial carcinoma. UPII, GATA3, and p40 were further tested for specificity in lung, breast, colon, kidney, and prostate cancers. In all invasive urothelial carcinoma cases, UPII, GATA3, p40, and p63 exhibited sensitivities of 77.7%, 83.5%, 85.4%, and 80.6%, respectively. The combination of UPII, GATA3, and p40 antibodies stained 94.2% (97/103) of all invasive urothelial carcinoma cases, including 92.2% (71/77) of grade 2-3 urothelial carcinomas. In addition, GATA3 and UPII showed negative staining in lung squamous cell carcinomas and p40 showed negative staining in breast infiltrating ductal carcinomas. The combination of UPII, GATA3, and p40 showed negative staining in lung adenocarcinoma, colon adenocarcinoma, and renal carcinomas. In conclusion, UPII, GATA3, and p40, when used in combination, are highly sensitive in the differential diagnosis of invasive urothelial carcinoma.

Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.

PubMed

Hanski, C; Hofmeier, M; Schmitt-Gräff, A; Riede, E; Hanski, M L; Borchard, F; Sieber, E; Niedobitek, F; Foss, H D; Stein, H; Riecken, E O

1997-08-01

Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P < 0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.

Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

PubMed

Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

2015-12-01

Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

Morphologic diversity of syringocystadenocarcinoma papilliferum based on a clinicopathologic study of 6 cases and review of the literature.

PubMed

Kazakov, Dmitry V; Requena, Luis; Kutzner, Heinz; Fernandez-Figueras, Maria Teresa; Kacerovska, Denisa; Mentzel, Thomas; Schwabbauer, Peter; Michal, Michal

2010-06-01

Syringocystadenocarcinoma papilliferum is an extremely rare cutaneous adnexal neoplasm. The purpose of our investigation was to study a series of syringocystadenocarcinoma papilliferum to document morphologic variations of the neoplasm. This is a light-microscopic study of 6 cases of syringocystadenocarcinoma papilliferum obtained from the combined archival, institutional, and consultations files of the authors over 60 years, complemented by a literature review. Syringocystadenocarcinoma papilliferum invariably occurred in association with syringocystadenoma papilliferum and presented as an in situ adenocarcinoma and/or invasive adenocarcinoma. Additionally, an invasive component was represented by squamous cell carcinoma. Variable present features included pagetoid migration of the neoplastic cells, dirty necrosis, mucinous ductal metaplasia, and ductal changes analogous to those seen in the breast. The ductal changes included patterns identical to columnar cell change (flat epithelial atypia), usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ. A combination of the above patterns in a single lesion was noted. It is concluded that morphologic diversity of syringocystadenocarcinoma papilliferum is substantial. Its association with the benign counterpart and ductal changes suggests a transformation that may involve usual ductal hyperplasia-atypical ductal hyperplasia-(ductal) adenocarcinoma in situ-invasive adenocarcinoma pathway.

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

PubMed

Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent

2018-05-21

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with

Invasive micropapillary carcinoma: a distinct type of adenocarcinomas in the gastrointestinal tract.

PubMed

Guzińska-Ustymowicz, Katarzyna; Niewiarowska, Katarzyna; Pryczynicz, Anna

2014-04-28

Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical ''inside-out'' structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization.

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

ClinicalTrials.gov

2018-06-08

Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lalani, Nafisha; Paszat, Lawrence; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario

Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databasesmore » and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF

Infrequent Loss of Luminal Differentiation in Ductal Breast Cancer Metastasis

PubMed Central

Calvo, Julia; Sánchez-Cid, Lourdes; Muñoz, Montserrat; Lozano, Juan José; Thomson, Timothy M.; Fernández, Pedro L.

2013-01-01

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. PMID:24205108

Multi-Institutional Experience of Ductal Carcinoma In Situ in Black vs White Patients Treated With Breast-Conserving Surgery and Whole Breast Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Carl; Bai, Harrison; Neboori, Hanmanth

2012-11-01

Purpose: Given the paucity of data on racial disparities in ductal carcinoma in situ (DCIS), the data from a multi-institutional cohort of DCIS patients treated with breast-conserving surgery and whole breast radiation therapy (RT) were analyzed to determine whether racial disparities or differences exist. Methods and Materials: A total of 533 white and 76 black DCIS patients from 3 university-based cancer centers were uniformly treated with breast-conserving surgery and RT. All patient data were collected and analyzed as a function of race. Results: The median follow-up was 5.2 years. No significant racial differences were seen in tumor size, age atmore » diagnosis, estrogen receptor status, necrosis, or grade (all P>.05). Of the treatment parameters, the RT dose delivered, boost, positive margin rates, frequency of hormone receptor status assessment, and receipt of hormonal therapy for the 2 cohorts did not significantly differ (all P>.05). The local relapse-free survival was similar at 5 years (96.1% and 98.1%, P=.399) and 10 years (92.8% vs 95.8%, P=.360), with no significant overall survival difference at 10 years (94.0% vs 88.9%, P=.290) between the white and black patients, respectively. On multivariate analysis, race was not an independent predictor of local relapse-free survival or overall survival when accounting for age, grade, and margin status. Conclusion: In our large cohort of DCIS patients uniformly treated at 3 institutions with breast conservation without any apparent differences in treatment delivery parameters, we demonstrated that the clinical and pathologic features and local survival outcomes did not differ as a function of race. Our results suggest that when black patients with DCIS are appropriately selected for breast conservation and receive adjuvant RT without racial disparities in the treatment parameters, differences in the outcomes as a function of race do not exist.« less

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

PubMed

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-11-19

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Electrical characteristics of Graphene based Field Effect Transistor (GFET) biosensor for ADH detection

NASA Astrophysics Data System (ADS)

Selvarajan, Reena Sri; Hamzah, Azrul Azlan; Majlis, Burhanuddin Yeop

2017-08-01

First pristine graphene was successfully produced by mechanical exfoliation and electrically characterized in 2004 by Andre Geim and Konstantin Novoselov at University of Manchester. Since its discovery in 2004, graphene also known as `super' material that has enticed many researchers and engineers to explore its potential in ultrasensitive detection of analytes in biosensing applications. Among myriad reported sensors, biosensors based on field effect transistors (FETs) have attracted much attention. Thus, implementing graphene as conducting channel material hastens the opportunities for production of ultrasensitive biosensors for future device applications. Herein, we have reported electrical characteristics of graphene based field effect transistor (GFET) for ADH detection. GFET was modelled and simulated using Lumerical DEVICE charge transport solver (DEVICE CT). Electrical characteristics comprising of transfer and output characteristics curves are reported in this study. The device shows ambipolar curve and achieved a minimum conductivity of 0.23912 e5A at Dirac point. However, the curve shifts to the left and introduces significant changes in the minimum conductivity as drain voltage is increased. Output characteristics of GFET exhibits linear Id - Vd dependence characteristics for gate voltage ranging from 0 to 1.5 V. In addition, behavior of electrical transport through GFET was analyzed for various simulation temperatures. It clearly proves that the electrical transport in GFET is dependent on the simulation temperature as it may vary the maximum resistance in channel of the device. Therefore, this unique electrical characteristics of GFET makes it as a promising candidate for ultrasensitive detection of small biomolecules such as ADH in biosensing applications.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

PubMed

Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

[Results of surgical treatment in ampullary and pancreatic carcinoma and its prognostic parameters after R0-resection].

PubMed

Ridwelski, K; Meyer, F; Schmidt, U; Lippert, H

2005-08-01

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic

Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?

PubMed

Hajaj, Mohamad; Karim, Ahmed; Pascaline, Sana; Noor, Lubna; Patel, Shivali; Dakka, Mahmoud

2017-10-01

Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery. Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful

A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors

ClinicalTrials.gov

2016-03-23

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Tumor Virus Infections

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

PubMed

Shield, Paul W; Papadimos, David J; Walsh, Michael D

2014-04-01

The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

PubMed

Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

2003-02-01

Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth Inhibitor...9 Fibroblast Growth Factor -2: an Epithelial Ductal Cell Growth Inhibitor that Drops Out in Breast Cancer

Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer

PubMed Central

Barr Fritcher, Emily G.; Degnim, Amy C.; Hartmann, Lynn C.; Radisky, Derek C.; Boughey, Judy C.; Anderson, Stephanie S.; Vierkant, Robert A.; Frost, Marlene H.; Visscher, Daniel W.; Reynolds, Carol

2011-01-01

Background Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. Methods ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967–1991. The ACISRIII (Dako, Carpinteria, CA) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared to the Iowa SEER control population. Results Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity [p<0.05]. ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. Conclusion We found increasing ER expression in atypical hyperplasia with increasing age. ER expression in atypical hyperplasia does not further discriminate breast cancer risk in women with atypia. PMID:21209395

Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma

PubMed Central

Kuo, Kung-Kai; Kuo, Chao-Jen; Chiu, Chiang-Yen; Liang, Shih-Shin; Huang, Chun-Hao; Chi, Shu-Wen; Tsai, Kun-Bow; Chen, Chiao-Yun; Hsi, Edward; Cheng, Kuang-Hung; Chiou, Shyh-Horng

2016-01-01

Objectives The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling. Methods Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion. Results Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, ≥2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include α-enolase, α-catenin, 14-3-3 β, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining. Conclusions The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC. PMID:26262590

NOGGIN IS REQUIRED FOR NORMAL LOBE PATTERNING AND DUCTAL BUDDING IN THE MOUSE PROSTATE

PubMed Central

Cook, Crist; Vezina, Chad M.; Hicks, Sarah M.; Shaw, Aubie; Yu, Min; Peterson, Richard E.; Bushman, Wade

2008-01-01

Mesenchymal expression of the BMP antagonist NOGGIN during prostate development plays a critical role in pre-natal ventral prostate development and opposes BMP4-mediated inhibition of cell proliferation during postnatal ductal development. Morphologic examination of newborn Noggin-/- male fetuses revealed genitourinary anomalies including cryptorchidism, incomplete separation of the hindgut from the urogenital sinus (UGS), absence of the ventral mesenchymal pad and a complete loss of ventral prostate (VP) budding. Examination of lobe-specific marker expression in the E14 Noggin-/- UGS rescued by transplantation under the renal capsule of a male nude mouse confirmed a complete loss of VP determination. More modest effects were observed in the other lobes, including decreased number of ductal buds in the dorsal and lateral prostates of newborn Noggin-/- males. BMP4 and BMP7 have been shown to inhibit ductal budding and outgrowth by negatively regulating epithelial cell proliferation. We show here that NOGGIN can neutralize budding inhibition by BMP4 and rescues branching morphogenesis of BMP4-exposed UGS in organ culture and show that the effects of BMP4 and NOGGIN activities converge on P63+ epithelial cells located at nascent duct tips. Together, these studies show that the BMP-NOGGIN axis regulates patterning of the ventral prostate, regulates ductal budding, and controls proliferation of P63+ epithelial cells in the nascent ducts of developing mouse prostate. PMID:18028901

Weight loss reduces breast ductal fluid estrogens in obese postmenopausal women: a single arm intervention pilot study.

PubMed

Carpenter, Catherine L; Duvall, Karen; Jardack, Patricia; Li, Luyi; Henning, Susanne M; Li, Zhaoping; Heber, David

2012-12-05

Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women. We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage. Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%). Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.

PubMed

Blair, Alex B; Zheng, Lei

2017-06-01

The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

PubMed Central

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-01-01

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001 PMID:24252877

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

PubMed Central

Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

2013-01-01

Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.

PubMed

Elshof, Lotte E; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A Elise; Skinner, Victoria P; Dif, Nicolas; Pijnappel, Ruud M; Bijker, Nina; Rutgers, Emiel J Th; Wesseling, Jelle

2015-08-01

The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Advanced Solid Tumors

ClinicalTrials.gov

2018-05-16

Small Cell Lung Carcinoma; Carcinoma, Squamous Cell of Head and Neck; Stomach Neoplasms; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Esophagogastric Junction Neoplasms; Carcinoma, Pancreatic Ductal; Esophageal Squamous Cell Carcinoma

A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis.

PubMed

Nealon, William H; Bhutani, Manoop; Riall, Taylor S; Raju, Gottumukkala; Ozkan, Orhan; Neilan, Ryan

2009-05-01

Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications.

Prognostic significance of p16INK4a/p53 in Tunisian patients with breast carcinoma.

PubMed

Karray-Chouayekh, Sondes; Baccouche, Sami; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Daoud, Jamel; Frikha, Mounir; Jlidi, Rachid; Gargouri, Ali; Mokdad-Gargouri, Raja

2011-09-01

Infiltrating ductal carcinoma (IDC) of the breast is a result of genetic alterations that affect the regulation of the cell cycle check-point and apoptosis. The aim of the present study was analysis using immunohistochemical localization of mouse double minute-2 (mdm2), p16INK4a, p53, bax and bcl-2 markers in Tunisian patients with breast IDC and to determine if there was correlation with the major clinico-pathological parameters and with survival of patients. We showed that the expression of p53, p16INK4a, mdm2, bcl-2, and bax was observed in 46.3%, 20.7%, 38%, 50% and 11.9% of cases, respectively. Statistical analysis revealed that positive expression of mdm2 was associated with larger tumors (P=0.013), whereas bax positivity was more prevalent in younger patients and in tumors of smaller size (P=0.008 and P=0.012 respectively). Furthermore, the expression of p16INK4a correlated with advanced grade (P<0.0001), triple negative tumors (ER-/PR-/HER2-, P=0.001) and mdm2 expression (P=0.017). The absence of nuclear p53 accumulation was predictive of good prognosis as well as when it was associated with negative expression of p16INK4a. Our findings suggest that among the biomarkers tested, p16INK4a might have a useful clinical and prognostic significance in infiltrating ductal carcinoma of the breast. Copyright © 2010 Elsevier GmbH. All rights reserved.

Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: Rate of upgrade to carcinoma at excision.

PubMed

Pareja, Fresia; Corben, Adriana D; Brennan, Sandra B; Murray, Melissa P; Bowser, Zenica L; Jakate, Kiran; Sebastiano, Christopher; Morrow, Monica; Morris, Elizabeth A; Brogi, Edi

2016-09-15

The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core-needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC). This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded. The radiologic and clinicopathologic features of patients with a CNB diagnosis of IDP were correlated with an upgrade to carcinoma at EXC. The study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent EXC. The upgrade rate was 2.3% (4 of 171). The upgraded lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥ 8 mm away. Twenty-four women (25 IDPs) did not undergo EXC and had stable imaging on follow-up (median, 23.5 months). The upgrade rate at EXC for IDPs diagnosed at CNB with radiologic-pathologic concordance was 2.3%. These findings suggest that observation is appropriate for patients with radiologic-pathologic concordant CNB yielding IDP, regardless of its size. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2819-2827. © 2016 American Cancer Society. © 2016 American Cancer Society.

Approach and management of primary ectopic breast carcinoma in the axilla: where are we? A comprehensive historical literature review.

PubMed

Visconti, Giuseppe; Eltahir, Yassir; Van Ginkel, Robert J; Bart, Joost; Werker, Paul M N

2011-01-01

Primary ectopic breast carcinoma is a rare disease and, at present, no specific guidelines on its diagnosis and treatment are available. The purpose of this article is to review the world literature in English on primary ectopic breast carcinoma located in the armpit and to offer guidelines for diagnosis and treatment. Data for this review were identified by searches of MEDLINE, PubMed, The Cochrane Library, ACNP (Italian catalogue of journals) and references from relevant articles using relevant search terms and data published in the previous reviews. Primary ectopic breast carcinoma of the axilla mostly affects women of over 40 (range 28-90 yrs) years of age. The most frequent histological diagnosis is invasive ductal carcinoma not otherwise specified (NOS) (72%). Because of its rareness, in most cases, the diagnosis is delayed for on average 40.5 months. This disease is rare, but a high level of suspicion for carcinoma is mandatory when confronted with a tumour in this area. Once diagnosed, patients should undergo staging, and prognostic and adjuvant treatment procedures identical to orthotopic breast carcinoma guidelines. There are some limitations for the staging. Loco-regional treatment, on indication, combined with endocrine therapy and/or chemotherapy seems the treatment of choice. Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Evolving concepts in the management of lobular neoplasia.