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Sample records for borderline ovarian tumor

  1. [Ovarian tumors of low malignant potential (borderline ovarian tumors)].

    PubMed

    Luchian, Alina-Mihaela; Pricop, M

    2011-01-01

    Ovarian borderline tumors are rare, their good prognosis depending on their stage at the time of diagnosis, and the presence of invasive implants. There is little information on tumor type identified intra-surgically, as well as on the most favorable treatment in borderline ovarian tumors. To determine the criteria of identification and presurgery and intra-surgery differentiation of the ovarian borderline tumors from the invasive carcinoma and benign ovarian tumors. This study included 54 patients with TPMS (ovarian borderline tumors) surgically treated in the past 22 years (January 1988-December 2009) at the 4th Gynecological Clinic of the lasi "Gr. T. Popa" University of Medicine and Pharmacy. In this interval 1,107 ovarian tumors: 575 benign, 478 malignant, and 54 TPMS (4.87%) were recorded. The age of the patients with borderline tumors ranged between 20 and 78 years, mean age 46 years, and the histological types were: mucinous (27 cases), serous (18 cases), mixed (8 cases), and Brenner tumor (1 case). We have analyzed the distribution of these cases according to the time when surgical treatment was performed. The frequency of borderline ovarian tumors in our study is 4.87%, lower than in the literature. We believe that this low percentage in our study is due to missing the microscopic data in some macroscopic benign tumors. By this research we aimed at elaborating a therapeutic strategy for each case using with discernment the modern treatment (surgery, chemotherapy, radiotherapy), as well as new chemical drugs with the goal of obtaining better results and longer survival. There are no tumor markers which could predict the progression of a borderline ovarian tumor to invasive tumors, but the invasive course is only 0.7%.

  2. Needleoscopic Conservative Staging of Borderline Ovarian Tumor.

    PubMed

    Gueli Alletti, Salvatore; Rossitto, Cristiano; Perrone, Emanuele; Cianci, Stefano; De Blasis, Ilaria; Fagotti, Anna; Scambia, Giovanni

    To investigate the safety and technical feasibility of needleoscopic fertility-sparing staging of borderline ovarian tumors. Video article and review of the literature (Canadian Task Force classification Level III). This 29-year-old woman had a right ovarian cyst suspicious for borderline ovarian tumor on preoperative magnetic resonance imaging and ultrasound showing the presence of a right unilocular ovarian cyst with a papillary projection. Informed consent for abdominal or laparoscopic approach was obtained from the patient in accordance with the local legislation. The patient also provided informed consent to use images and videos of the procedure. Institutional Review Board approval was not required for this kind of procedure. Treatment involved conservative staging with right ovarian cystectomy, peritoneal biopsies, infracolic omental biopsy, and peritoneal cytology. Instrumentation included two 2.4-mm needleoscopic instruments. The total operative time was 62 minutes, and estimated blood loss was <10 mL. No intraoperative complications were recorded. At the end of the surgical procedure, the outer diameter of the incision was increased by only up to 3 mm. The patient was discharged the day after the procedure. Histopathological analysis confirmed a serous borderline ovarian tumor. A 30 days postoperative follow-up, a satisfactory cosmetic result was reported by both the patient (score of 10 of out of a possible 10) and the surgeon (10 of 10). To the best of our knowledge, there are no previously published reports of needleoscopic treatment of borderline ovarian tumor, which represents a great challenge for ultra-minimally invasive approaches [1-3]. Based on our initial experience, the needleoscopic instruments could prove to be a beneficial tool in adnexal benign or borderline disease. At present, only a hybrid operative setting should be considered to overcome the lack of bipolar energy [4-6]. Further studies are needed to define the benefits

  3. Borderline ovarian tumors: a review of treatment.

    PubMed Central

    Chambers, J. T.

    1989-01-01

    Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863

  4. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    PubMed

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

    PubMed Central

    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  6. Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

    PubMed

    Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken

    2015-05-01

    Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

  7. Long-term survival in women with borderline ovarian tumors: a population-based survey of borderline ovarian tumors in Sweden 1960-2007.

    PubMed

    Kalapotharakos, Grigorios; Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer

    2016-04-01

    We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden. All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis. The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121). Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  9. Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings

    PubMed Central

    Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta

    2016-01-01

    Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412

  10. Pregnancy after fertility-sparing surgery for borderline ovarian tumors.

    PubMed

    Lian, Chengying; Chen, Xiujuan; Ni, Yihua; Huang, Xiaochen; Lin, Yuan

    2016-09-01

    To investigate the ability to conceive and the factors affecting chances of pregnancy among patients with borderline ovarian tumors (BOTs) treated with fertility-sparing surgery. A retrospective study included nulliparous patients aged 40years or younger who had undergone fertility-sparing surgery for BOTs between January 2005 and June 2012 at a center in Fuzhou, China. Identified patients were followed up by telephone or mail between March 15 and June 30, 2013. Patients who had already been pregnant and those who had not but had discontinued contraception for more than 1year were included in final analyses. Among 23 included patients, 17 (74%) had become pregnant within the mean follow-up period of 48.2months. The frequencies of previous infertility, sequelae of pelvic inflammatory disease, and endometriosis were all higher in the nonpregnant group than in the pregnant group (P≤0.021 for all). More women in the nonpregnant group that in the pregnant group had BOTs of stage II or worse, but the difference was nonsignificant (P=0.059). Fertility-sparing surgery in young patients with BOTs is associated with a good pregnancy rate. However, the tumor stage and coexisting infertility factors are important considerations in selecting the optimal surgical approach. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  11. The molecular pathology of ovarian serous borderline tumors.

    PubMed

    Malpica, A; Wong, K-K

    2016-04-01

    Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.

  12. [Borderline ovarian tumors and global radiation in relation with climate change impact].

    PubMed

    Luchian, Alina-Mihaela; Pricop, M

    2011-01-01

    There is limited information on borderline ovarian tumor detected intra-surgically and its most favorable treatment in relation with global radiation and climate changes. To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iaşi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors.

  13. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  14. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report.

    PubMed

    Takemoto, Shuji; Kawano, Ryosuke; Honda, Kazumi; Nakazono, Aki; Shimamatsu, Kazuhide

    2012-05-14

    Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

  15. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report

    PubMed Central

    2012-01-01

    Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery. PMID:22583977

  16. p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.

    PubMed

    Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria

    2016-10-22

    Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05. p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the

  17. Ovarian serous borderline tumors with noninvasive and invasive peritoneal implants: A case report each.

    PubMed

    Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao

    2015-01-01

    Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.

  18. A case-control study of borderline ovarian tumors: the influence of perineal exposure to talc.

    PubMed

    Harlow, B L; Weiss, N S

    1989-08-01

    The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used.

  19. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria.

    PubMed

    Hauptmann, Steffen; Friedrich, Katrin; Redline, Raymond; Avril, Stefanie

    2017-02-01

    Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Since BOT were first identified >40 years ago, they have inspired controversies disproportionate to their incidence. This review discusses diagnostic criteria for the histologic subtypes of BOT, highlighting areas of diagnostic challenges, ongoing controversies, and changes in terminology implemented by the recent 2014 WHO Classification of Tumours of the Female Genital Organs. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. Serous borderline tumors (SBT) share molecular and genetic alterations with low-grade serous carcinomas and can present at higher stages with peritoneal implants and/or lymph node involvement, which validates their borderline malignant potential. All other (non-serous) subtypes of BOT commonly present at stage I confined to the ovary(ies) and are associated with overall survival approaching that of the general population. An important change in the WHO 2014 classification is the new terminology of non-invasive implants associated with SBT, as any invasive foci (previously called "invasive implants") are now in line with their biological behavior considered peritoneal low-grade serous carcinoma (LGSC). The controversy regarding the terminology of non-serous borderline tumors, called by some pathologists "atypical proliferative tumor" in view of their largely benign behavior, has not been resolved. The concepts of intraepithelial carcinoma and microinvasion may evolve in further studies, as their presence appears to have no prognostic impact and is subject to considerable inter-observer variability.

  20. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  1. Borderline ovarian tumors: a study of 100 cases from a Tertiary Care Hospital

    PubMed Central

    Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.

    2013-01-01

    Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520

  2. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  3. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  4. Ultrasonographic diagnosis and longitudinal follow-up of recurrences after conservative surgery for borderline ovarian tumors.

    PubMed

    Franchi, Dorella; Boveri, Sara; Radice, Davide; Portuesi, Rosalba; Zanagnolo, Vanna; Colombo, Nicoletta; Testa, Antonia Carla

    2016-12-01

    Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline

  5. Decision making in borderline ovarian tumors: report of a rare case of mesosigma psammocarcinoma.

    PubMed

    Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella

    2013-09-03

    Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.

  6. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors.

    PubMed

    El Din, Amina A Gamal; Badawi, Manal A; Aal, Shereen E Abdel; Ibrahim, Nihad A; Morsy, Fatma A; Shaffie, Nermeen M

    2015-12-15

    Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.

  7. Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.

    PubMed

    Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2015-10-01

    Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.

  8. Differentiation between borderline and benign ovarian tumors: combined analysis of MRI with tumor markers for large cystic masses (≥5 cm).

    PubMed

    Park, Sung Yoon; Oh, Young Taik; Jung, Dae Chul

    2016-05-01

    There is overlap in imaging features between borderline and benign ovarian tumors. To analyze diagnostic performance of magnetic resonance imaging (MRI) combined with tumor markers for differentiating borderline from benign ovarian tumor. Ninety-nine patient with MRI and surgically confirmed ovarian tumors 5 cm or larger (borderline, n = 37; benign, n = 62) were included. On MRI, tumor size, septal number (0; 1-4; 5 or more), and presence of solid portion such as papillary projection or septal thickening 0.5 cm or larger were investigated. Serum tumor markers (carbohydrate antigen 125 [CA 125] and CA 19-9) were recorded. Multivariate analysis was conducted for assessing whether combined MRI with tumor markers could differentiate borderline from benign tumor. The diagnostic performance was also analyzed. Incidence of solid portion was 67.6% (25/37) in borderline and 3.2% (2/62) in benign tumors (P < 0.05). In all patients, without combined analysis of MRI with tumor markers, multivariate analysis revealed solid portion (P < 0.001) and CA 125 (P = 0.039) were significant for predicting borderline tumors. When combined analysis of MRI with CA 125 ((i) the presence of solid portion or (ii) CA 125 > 44.1 U/mL with septal number ≥5 for borderline tumor) is incorporated to multivariate analysis, it was only significant (P = 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of combined analysis of MRI with CA 125 were 89.1%, 91.9%, 86.8%, 93.4, and 90.9%, respectively. Combined analysis of MRI with CA 125 may allow better differentiation between borderline and benign ovarian tumor compared with MRI alone. © The Foundation Acta Radiologica 2015.

  9. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

    PubMed

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

    2015-01-01

    Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

  10. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  11. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies.

    PubMed

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna; Bandera, Elisa V; Doherty, Jennifer A; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Edwards, Robert P; Schildkraut, Joellen M; Berchuck, Andrew; Olson, Sara H; Kiemeney, Lambertus A; Massuger, Leon F A G; Narod, Steven A; Phelan, Catherine M; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H; Pearce, Celeste L; Risch, Harvey A; Jensen, Allan

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. May increased CA125 in borderline ovarian tumor be indicative of a poor prognosis? A case report.

    PubMed

    Anastasi, Emanuela; Porpora, Maria Grazia; Pecorella, Irene; Bernardo, Silvia; Frati, Luigi; Benedetti Panici, Pierluigi; Manganaro, Lucia

    2014-07-01

    We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).

  13. Epidemiologic features of borderline ovarian tumors in California: a population-based study.

    PubMed

    Morris, Cyllene R; Liu, Lihua; Rodriguez, Anne O; Cress, Rosemary D; Snipes, Kurt

    2013-04-01

    Borderline ovarian tumors (BOT) became no longer reportable in 2001, and few registries still collect information on these still poorly understood tumors. This study's objective was to describe epidemiologic features, trends, and survival of BOTs compared with those of low-grade (LG) and high-grade (HG) epithelial ovarian cancer (EOC) in the large and diverse population of California. Data from the California Cancer Registry were used to examine demographic and tumor characteristics among women diagnosed with BOT (n = 9,786), LG-EOC (n = 3,656), and HG-EOC (n = 40,611) from 1988 to 2010. Annual percent changes in BOT and LG-EOC incidence rates were estimated using Joinpoint regression; 5-year relative survival was calculated for both BOTs and LG-EOCs by age, race/ethnicity, and histology. Age-adjusted incidence rates of BOT in 2009 were 3.1, 2.3, 2.2, and 1.4 per 100,000 among whites, Latinas, African Americans, and Asian/Pacific Islanders, respectively. Incidence rates for LG-EOC decreased by 2.2 % per year; rates for BOT increased by 7.3 % per year until 1993, remained unchanged until 2006, and seemed to decline thereafter. Compared with LG-EOCs, BOTs were diagnosed in higher frequency among Latinas, at younger age, and were more likely to affect only one ovary. Overall, 5-year relative survival for BOT was 98.9 %; among women diagnosed with stage IV BOT, survival was 77.1 %. In this study, differences between BOTs and LG-EOCs were marked but varied substantially by histologic subtype and were far less dramatic than differences between BOTs and HG-EOCs. Findings underscore the importance of understanding these enigmatic tumors.

  14. Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: A nationwide population-based cohort study.

    PubMed

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K

    2016-11-01

    Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype-specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Coexistence of borderline ovarian epithelial tumor, primary pelvic hydatid cyst, and lymphoepithelioma-like gastric carcinoma.

    PubMed

    Gungor, Tayfun; Altinkaya, Sunduz Ozlem; Sirvan, Levent; Lafuente, Roberto Alvarez; Ceylaner, Serdar

    2011-06-01

    Borderline ovarian tumors (BOTs) represent a heterogeneous group of ovarian epithelial neoplasms. Despite a favorable prognosis, 10-20% of BOTs exhibit progressively worsening clinic. Primary involvement of pelvic organs with echinococcus is very rare. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach. A 58-year-old woman referred with abdominal swelling and gastric complaints. Imaging studies revealed a huge cystic mass with multiple septations and solid component, another cystic mass with an appearance of cyst hydatid in the pelvis, and thickening of the small curvature of stomach. Gastroscopy revealed an ulcer with a suspicious malignant appearance, and histology of the endoscopic specimen showed severe chronic inflammation and lymphocytic infiltration. No other involvement of hydatid cyst was detected. In the exploration, there was a 25cm cystic lesion with solid components arising from right ovary, another 6cm cyst over the former, 7cm cystic lesion arising from left ovary, and 10cm mass near the small curvature of the stomach. Excision of the masses; total gastrectomy with esophagojejunal anastomosis; total abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy; appendectomy; splenectomy; and pelvic, paraaortic, and coeliac lympadenectomy were performed. Final pathology revealed lymphoepithelioma-like gastric carcinoma, bilateral serous BOT, and hydatid cyst. Hydatid cyst should always be considered in the differential diagnosis of abdominopelvic masses in endemic regions of the world. Preoperative diagnosis of primary pelvic hydatid disease is difficult and awareness of its possibility is very important especially in patients residing in or coming from endemic areas. Copyright © 2011. Published by Elsevier B.V.

  16. The effect of hysterectomy on survival of patients with borderline ovarian tumors.

    PubMed

    Menczer, Joseph; Chetrit, Angela; Sadetzki, Siegal

    2012-05-01

    The classically recommended surgical treatment of borderline ovarian tumors (BOTs) includes hysterectomy in addition to bilateral adnexectomy. Possible reasons for hysterectomy might be a high frequency of uterine involvement and its favorable effect on survival. The purpose of the present study was to assess the frequency of uterine involvement in patients with BOTs and the effect of hysterectomy on survival. All incident cases of histological confirmed BOTs diagnosed in Israeli Jewish women between March 1 1994 and June 30 1999, were identified. Clinical and pathological characteristics were abstracted from medical records. Patients with tumors grossly confined to the ovaries (apparently stage I) were considered to have had surgical staging when at least hysterectomy, bilateral salpingooophorectomy, omentectomy and pelvic lymph node sampling were done. The study group comprised 225 patients. Hysterectomy was performed in 147 (65.31%) patients and uterine involvement was present in only 3 (2.0%) of them. The 13 year survival of the total group of patients was 85.8% and of those in apparent stage I, 88.5%. Among patients with tumors apparently confined to the ovaries, no significant survival difference was observed between unstaged and surgically staged patients. There was also no survival difference between the overall staged and unstaged patients and between patients in stages II-III who did and did not undergo hysterectomy. Our data indicate that the rate of uterine involvement in BOT is low and that hysterectomy does not favorably affect survival. The necessity of hysterectomy in BOT patients is questioned. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status.

    PubMed

    Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia; Derchain, Sophie

    2013-04-01

    To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.

  18. Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status

    PubMed Central

    Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia

    2013-01-01

    Objective To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. Methods We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Results Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Conclusion Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression. PMID:23653835

  19. Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

    PubMed

    Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

    2013-07-09

    Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

  20. Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers

    PubMed Central

    Danilewicz, Marian; Suzin, Jacek; Wagrowska-Danilewicz, Malgorzata; Spych, Michal; Tylinski, Wieslaw; Topczewska-Tylinska, Katarzyna; Piekarski, Janusz; Kazmierczak-Lukaszewicz, Sylwia; Cialkowska-Rysz, Aleksandra

    2013-01-01

    Introduction There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. Material and methods The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. Results sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. Conclusions sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven. PMID:23515230

  1. Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.

    PubMed

    Emmanuel, Catherine; Chiew, Yoke-Eng; George, Joshy; Etemadmoghadam, Dariush; Anglesio, Michael S; Sharma, Raghwa; Russell, Peter; Kennedy, Catherine; Fereday, Sian; Hung, Jillian; Galletta, Laura; Hogg, Russell; Wain, Gerard V; Brand, Alison; Balleine, Rosemary; MacConaill, Laura; Palescandolo, Emanuele; Hunter, Sally M; Campbell, Ian; Dobrovic, Alexander; Wong, Stephen Q; Do, Hongdo; Clarke, Christine L; Harnett, Paul R; Bowtell, David D L; deFazio, Anna

    2014-12-15

    Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. ©2014 American Association for Cancer Research.

  2. Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

    PubMed

    Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

    2017-02-01

    We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

  3. HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by immunohistochemistry and fluorescence in situ hybridization.

    PubMed

    Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M

    2004-01-01

    The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.

  4. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2016-10-20

    Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer

  5. Postpubertal Persistent Hyperestrogenemia in McCune-Albright Syndrome: Unilateral Oophorectomy Improved Fertility but Detected an Unexpected Borderline Epithelial Ovarian Tumor.

    PubMed

    Chevalier, Nicolas; Paris, Françoise; Fontana, Sylvie; Delotte, Jérôme; Gaspari, Laura; Ferrari, Patricia; Sultan, Charles; Fénichel, Patrick

    2015-12-01

    McCune-Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization-induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  6. Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors

    PubMed Central

    2012-01-01

    Background In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors. Methods Total of 68 ovarian tumors, 25 benign [13 (19.1%) serous and12 (17.6%) mucinous], 16 borderline [9 (13.2%) serous and 7(10.3%) mucinous], and 27 malignant ovarian tumors [24 (35.3%) serous and 3 (4.4%) mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl–2, telomerase, c-kit, and metallothionein were evaluated. Results When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p < 0.05). After evaluation of all 68 cases, the serous tumors showed significantly higher staining scores of p53, p21, c-kit, and metallothionein compared to the mucinous ones (p < 0.05). For differentiation of benign and borderline and malignant tumors combined, p53 was not used because all benign tumors has no staining, and p21, bax, and metallothionein was determined the significant predictors for borderline and malignant tumors combined (p < 0.05). For differentiation of borderline and malignant tumors, only p53 was determined the significant predictor for malignant tumors (p < 0.05). Conclusions In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and

  7. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  8. Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata.

    PubMed

    Yahata, Tetsuro; Banzai, Chiaki; Tanaka, Kenichi

    2012-04-01

    The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan. Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007. A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983-1989) to 3.5 (2000-2007) per 100,000 females. This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  9. An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.

    PubMed

    Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia

    2014-01-01

    Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

  10. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

  11. Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

    PubMed

    Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

    2017-05-11

    The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinico-pathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinico-pathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We

  12. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    PubMed

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-02-06

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

  13. Population-based cohort follow-up study of all patients operated for borderline ovarian tumor in western Sweden during an 11-year period.

    PubMed

    Akeson, M; Zetterqvist, B-M; Dahllöf, K; Jakobsen, A-M; Brännström, M; Horvath, G

    2008-01-01

    Borderline ovarian tumors (BOTs) make up around 10-20% of all epithelial ovarian tumors. The aim of the present study was to investigate the outcome of a complete large population-based cohort of patients treated for BOT. All patients (n= 399) treated for BOT in the western part of Sweden (population around 1.6 million) between 1993 and 2004 were followed. The treatment consisted of primary staging surgery with addition of platinum-based adjuvant chemotherapy for the majority of aneuploid tumors. Data relating to the surgical procedure, FIGO stage, histopathology, ploidy status, adjuvant chemotherapy, and disease state (recurrence or death) at follow-up visits were continuously entered into a cancer quality registry. Data concerning cases and deaths were also controlled against the Swedish National Cancer Registry. The median age of the BOT patients was 55 years (range 16-90). The relative 5- and 10-year survivals were 99.9% (95% CI 96.3-102.4) and 103.5% (95% CI 97.2-108.2), respectively. Aneuploidy was found in 63 (17%) patients, with significantly more aneuploid tumors found among patients of older (>60 years) age. Out of the 399 patients, 8 had recurrence of the disease. Three of the eight patients died from the disease. Five patients with recurrence are alive, three of these patients with no signs of disease after additional treatment. This complete long-term follow-up of a large population-based cohort of BOT patients shows that there is a good overall survival in this patient group.

  14. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

    PubMed

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

    2017-03-01

    Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

    PubMed

    Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

    2014-11-01

    Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

  16. Diagnosis problems in a case of ovarian tumor - case presentation.

    PubMed

    Albu, Dinu Florin; Albu, Cristina CrenguŢa; Văduva, Constantin Cristian; Niculescu, Mihaela; Edu, Antoine

    2016-01-01

    Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.

  17. Ovarian Germ Cell Tumors Treatment

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health Professional Version Key Points ...

  18. Principles of Treatment for Borderline, Micropapillary Serous, and Low-Grade Ovarian Cancer.

    PubMed

    Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn

    2016-09-01

    Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired. Copyright © 2016 by the National Comprehensive Cancer Network.

  19. Serous borderline tumor of the fallopian tube presented as hematosalpinx: a case report

    PubMed Central

    Krasevic, Maja; Stankovic, Teodora; Petrovic, Oleg; Smiljan-Severinski, Neda

    2005-01-01

    Background Compared with their ovarian counterparts, serous borderline tumors of the fallopian tube are uncommon, with limited experience about their clinical behaviour. We present a case of serous borderline tumor of the fallopian tube with unusual presentation and summarise all the published cases to date. Case presentation A case of serous borderline tumor of the fallopian tube in a 34-year old patient is presented, incidentally found during routine gynecologic examination. At laparoscopy the tumor was unusualy presented as hematosalpinx and was treated by salpingectomy. Cell-cycle analysis of the tumor tissue revealed a diploid DNA content and a low S-phase fraction. There was no evidence of the disease during the follow-up period of 4.6 years. Conclusion The current case and review of the literature suggest salpingectomy as the optimal treatment for patients with serous borderline tumor of the fallopian tube. PMID:16212662

  20. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    PubMed Central

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Objective Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Methods Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. Results 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. Conclusions These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast

  1. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    PubMed

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and

  2. [Ovarian fibrothecal tumor: case report].

    PubMed

    González Gleason, Alejandro; De la Cruz, Sebastián Iris; Torres Salas, María Esther; Guzmán Patraca, Carlos; Chavarría Olarte, María Eugenia; Reyes Fuentes, Alejandro

    2002-05-01

    Tumors with stromal or sex-cords origin are scarce, and comprise only 5% or less of all ovarian tumors. Nevertheless functional tumor types are the most striking ones, only few of them produce hormonal symptoms. Fibrothecal tumors belong to the stromal cells tumor class, with differentiation towards both fibroblastic-type cells of thecal cell. We present a case report of a 68 years old woman with an ovarian tumor sized 14 x 9 x 7 cm. The treatment was the extirpation of the tumor. Microscopic evaluation of the surgical piece reported an ovarian fibrothecal tumor.

  3. Interventions for the treatment of borderline ovarian tumours

    PubMed Central

    Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral

  4. Epithelial membrane protein 1 expression in ovarian serous tumors.

    PubMed

    Demirag, Guzin Gonullu; Kefeli, Mehmet; Kemal, Yasemin; Yucel, Idris

    2016-03-01

    The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.

  5. A retrospective analysis of twenty-eight borderline ovarian tumours in adolescent girls.

    PubMed

    Tsikouras, P; Liberis, V; Galazios, G; Panagiotidou, C; Bouchlariotou, S; Teichmann, A T; Maroulis, G

    2009-01-01

    The aim of this retrospective study was to evaluate the clinical reproductive outcome and the rate of recurrence of low malignant ovarian tumors in adolescent girls after conservative surgical treatment by laparoscopy or laparotomy. We report 28 cases of borderline ovarian tumors (BOTs), that were surgically treated from 1990 to 2006 at the Obstetrical and Gynecological Department of Democritus University in Greece and the Aschaffenburg Teaching Hospital in Germany. All patient information was obtained by reviewing hospital records. BOT lesions in teenagers were associated with variable non-specific presenting symptoms. Ultrasonographic investigations can be helpful in the early diagnosis of BOTs in teenage girls. Most of the patients were diagnosed at an early stage. Available data of our study indicate that in these patients, fertility, pregnancy outcome and survival remain excellent.

  6. Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

    PubMed

    Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

    2000-11-01

    Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

  7. Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer.

    PubMed

    Ofinran, Olumide; Bose, Ujjal; Hay, Daniel; Abdul, Summi; Tufatelli, Cristina; Khan, Raheela

    2016-12-01

    The use of reference genes is the most common method of controlling the variation in mRNA expression during quantitative polymerase chain reaction, although the use of traditional reference genes, such as β‑actin, glyceraldehyde‑3‑phosphate dehydrogenase or 18S ribosomal RNA, without validation occasionally leads to unreliable results. Therefore, the present study aimed to evaluate a set of five commonly used reference genes to determine the most suitable for gene expression studies in normal ovarian tissues, borderline ovarian and ovarian cancer tissues. The expression stabilities of these genes were ranked using two gene stability algorithms, geNorm and NormFinder. Using geNorm, the two best reference genes in ovarian cancer were β‑glucuronidase and β‑actin. Hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase were the most stable in ovarian borderline tumours, and hypoxanthine phosphoribosyltransferase‑1 and glyceraldehyde‑3‑phosphate dehydrogenase were the most stable in normal ovarian tissues. NormFinder ranked β‑actin the most stable in ovarian cancer, and the best combination of two genes was β‑glucuronidase and β‑actin. In borderline tumours, hypoxanthine phosphoribosyltransferase‑1 was identified as the most stable, and the best combination was hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase. In normal ovarian tissues, β‑glucuronidase was recommended as the optimum reference gene, and the most optimum pair of reference genes was hypoxanthine phosphoribosyltransferase‑1 and β‑actin. To the best of our knowledge, this is the first study to investigate the selection of a set of reference genes for normalisation in quantitative polymerase chain reactions in different ovarian tissues, and therefore it is recommended that β‑glucuronidase, β‑actin and hypoxanthine phosphoribosyltransferase‑1 are the most suitable reference genes for such analyses.

  8. SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

    PubMed

    Moh, Michelle; Krings, Gregor; Ates, Deniz; Aysal, Anil; Kim, Grace E; Rabban, Joseph T

    2016-03-01

    The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric

  9. Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

    PubMed

    Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-05-01

    Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were

  10. Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination

    PubMed Central

    Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi

    2015-01-01

    Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849

  11. Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

    PubMed Central

    Tello, Mariela; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan

    2015-01-01

    Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123

  12. Treatment Option Overview (Ovarian Germ Cell Tumors)

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health Professional Version Key Points ...

  13. General Information about Ovarian Germ Cell Tumors

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health Professional Version Key Points ...

  14. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma.

    PubMed

    Laury, Anna R; Hornick, Jason L; Perets, Ruth; Krane, Jeffrey F; Corson, Joseph; Drapkin, Ronny; Hirsch, Michelle S

    2010-05-01

    Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker

  15. The accuracy of frozen section by tumor weight for ovarian epithelial neoplasms.

    PubMed

    Puls, L; Heidtman, E; Hunter, J E; Crane, M; Stafford, J

    1997-10-01

    This study evaluated the effect ovarian weight has on the accuracy of frozen sections in serous and mucinous ovarian tumors. The study group included 294 patients who had an initial frozen section (189 serous and 105 mucinous tumors) at surgery. The pathology reports were separated into subgroups (benign, borderline, or malignant). Tumors were broken down into three weight categories: < or = 450 g, > 450 to < or = 1360 g, and > 1360 g. In each weight category, accuracy, sensitivity, specificity, and positive and negative predicative values were calculated on frozen sections. The mean weight of the ovarian tumors was 1042 g. As the weight increased in serous tumors, the sensitivity fell from 96.2 to 93.8 to 75%, respectively, in each weight category. The same trend was noted with mucinous tumors as sensitivity fell from 91.7 to 87.5 to 66.7%, respectively. With an increase in the size of ovarian tumors, a decrease in the sensitivity of frozen section was observed. With tumors greater than 1360 g, sensitivity was only 69%. Twenty-three percent of ovarian tumors revealing borderline diagnosis at frozen section were malignant on the final pathology report, with the greatest misclassification in > 1360-g mucinous tumors (50%). For patients with large ovarian tumors, consideration should be given to performing staging at the time of the initial laparotomy.

  16. Prior appendectomy does not protect against subsequent development of malignant or borderline mucinous ovarian neoplasms.

    PubMed

    Elias, Kevin M; Labidi-Galy, S Intidhar; Vitonis, Allison F; Hornick, Jason L; Doyle, Leona A; Hirsch, Michelle S; Cramer, Daniel W; Drapkin, Ronny

    2014-02-01

    Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. From the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases. National Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman 'Tina's Wish' Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute - Susan Smith Center for

  17. Paired box gene 2 is associated with estrogen receptor α in ovarian serous tumors: Potential theory basis for targeted therapy.

    PubMed

    Wang, Min; Ma, Haifen

    2016-08-01

    It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors.

  18. Diagnostic potential of tumor DNA from ovarian cyst fluid

    PubMed Central

    Wang, Yuxuan; Sundfeldt, Karin; Mateoiu, Constantina; Shih, Ie-Ming; Kurman, Robert J; Schaefer, Joy; Silliman, Natalie; Kinde, Isaac; Springer, Simeon; Foote, Michael; Kristjansdottir, Björg; James, Nathan; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Vogelstein, Bert

    2016-01-01

    We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions. DOI: http://dx.doi.org/10.7554/eLife.15175.001 PMID:27421040

  19. Borderline ovarian tumours: clinical analysis of 38 cases.

    PubMed

    Behtash, N; Modares, M; Abolhasani, M; Ghaemmaghami, F; Mousavi, M; Yarandi, F; Hanjani, P

    2004-02-01

    Thirty-eight patients with ovarian tumours of low malignant potential (borderline) were diagnosed and treated in Tehran University Gynecology Oncology Department from 1991 to 2002, and have been reviewed. In this study age, clinical behavior, symptoms, surgical stage, type of tumour, surgery, adjuvant treatment, survival and recurrences were evaluated. A retrospective chart review was performed on these 38 patients who were treated for histopathologically confirmed tumours of low malignant potential between 1991-2002. The mean age was 34.4 years, range (14-83) (SD: 18.33). Post surgical FIGO staging was: Stage I=93.75%, stage III 6.25%. Histologic subtypes were: Serous 76.31% (29 patients), Mucinous 21.05% (8 patients), Mixed types 2.63% (1 patient). Mean pre-operative CA125 value was 114.90 (SD: +/- 90.30). Thirty-three percent of patients had only a simple cyst in ultrasonography. Conservative surgery was performed in 76.32% (29 patients). More radical surgery (TAH + BSO) was performed in 9 patients (23.68%). There were 6 recurrences. Three patients with recurrence and invasive implants received chemotherapy and secondary surgery was performed. Survival rate was 100% at 3 years for all stages and 89% at 5 years. One patient died of recurrent disease at 48 months after initial diagnosis. Our data suggest that LMP tumours are most frequently diagnosed in stage I. Most common histological type was serous, and 5 of the recurrences of (6 patients) were initially diagnosed at stage I, and had been treated with conservative surgery with no adjuvant therapy.

  20. Borderline and malignant phyllodes tumors display similar promoter methylation profiles.

    PubMed

    Kim, Jo-Heon; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han

    2009-12-01

    Mammary phyllodes tumors (PTs) are uncommon fibroepithelial neoplasms. On the basis of histologic criteria, PTs can be divided into benign, borderline, and malignant groups; however, the histologic distinction of PTs is often difficult and arbitrary. In breast cancer, promoter hypermethylation is a common phenomenon, but there are no data available concerning methylation status in PTs. The aim of this study was to assess whether the methylation profiles support the classification of PTs into three subgroups. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of five genes (GSTP1, HIN-1, RAR-beta, RASSF1A, and Twist) in 87 PTs (54 benign, 23 borderline, and 10 malignant). Immunohistochemical staining for GSTP1 was performed using tissue microarray blocks to determine whether GSTP1 promoter hypermethylation correlated with loss of GSTP1 expression. There was a trend of increasing methylation frequency with increasing grade of PTs. The methylation frequency of all genes and the mean number of methylated genes in borderline and malignant PTs were higher than those in benign PTs; however, there were no statistically significant differences between borderline and malignant PTs. GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.001). These results suggest that PTs segregate into only two groups on the basis of their methylation profiles: the benign group and the combined borderline/malignant group.

  1. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

  2. Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

    PubMed

    Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

    2016-06-15

    Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.

  3. Novel Treatment Shrinks Ovarian Tumors in Mice

    Cancer.gov

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  4. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    PubMed

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  5. Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

    PubMed

    Yoshida, Adriana; Derchain, Sophie Françoise; Pitta, Denise Rocha; Andrade, Liliana Aparecida Lucci De Angelo; Sarian, Luis Otavio

    2016-03-01

    To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%. Copyright © 2016. Published by Elsevier Inc.

  6. Requirement for expert histopathological assessment of ovarian cancer and borderline tumours

    PubMed Central

    Sengupta, P S; Shanks, J H; Buckley, C H; Ryder, W D J; Davies, J; Reynolds, K; Slade, R J; Kitchener, H C; Jayson, G C

    2000-01-01

    The distinction between borderline ovarian tumours (BOT) and ovarian carcinoma is made by histopathological assessment. Of 64 patients managed according to institutional BOT protocols, 27 (42%) had been referred with a diagnosis of ovarian carcinoma that was subsequently changed to BOT following histopathological review. The 70% 6-year event-free survival of the patients with a revised diagnosis was not significantly different from those who were referred with a diagnosis of BOT. This change in diagnosis is important as it avoids the need for chemotherapy for most patients and results in patients receiving appropriate information concerning prognosis. Interestingly, 24 patients (38.1%) reported a family history of epithelial cancer, a finding that has not been reported previously.© 2000 Cancer Research Campaign PMID:10732741

  7. Expression of p16, p53, CD24, EpCAM and calretinin in serous borderline tumors of the ovary.

    PubMed

    Aktaş, Işıl Yildiz; Buğdayci, Meral; Usubütün, Alp

    2012-01-01

    According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core. For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tumors while expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24 expression was detected in cases with peritoneal implants, favoring the theory that change of expression localization of cell adhesion molecules is in accordance with phenotypical changes and tumor progresssion. Furthermore, circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was detected in neoplastic cells in lymph nodes and microinvasion areas. Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin.

  8. Dub3 expression correlates with tumor progression and poor prognosis in human epithelial ovarian cancer.

    PubMed

    Zhou, Bo; Shu, Bin; Xi, Tao; Su, Ning; Liu, Jing

    2015-03-01

    Dub3 is a deubiquitinating enzyme. It is highly expressed in tumor-derived cell lines and has an established role in tumor proliferation. However, the role of Dub3 in human ovarian cancer remains unclear. Expression of Dub3 was evaluated in ovarian cancer tissues and cell lines by immunohistochemistry and Western blot analysis. The relationship between Dub3 expression and clinicopathological characteristics was analyzed. Using RNA interference, the effects of Dub3 on cell proliferation and apoptosis were investigated in ovarian cancer cell line. All normal ovary tissues exhibited very little or no Dub3 immunoreactivity. High levels of Dub3 expression were examined by immunohistochemical analysis in 13.3% of cystadenomas, in 30.0% of borderline tumors, and in 58.9% of ovarian carcinomas, respectively. Dub3 expression was significantly associated with lymph node metastasis and clinical staging (P<0.05). Multivariate survival analysis indicated that Dub3 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, the expression of Cdc25A was closely correlated with that of Dub3 in cancer cells and tissues. Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis. These data indicate that the Dub3 might be a valuable biomarker for the prediction of ovarian cancer prognosis and Dub3 inhibition might be a potential strategy for ovarian cancer treatment.

  9. Tumor infiltrating lymphocytes in ovarian cancer.

    PubMed

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  10. Tumor infiltrating lymphocytes in ovarian cancer

    PubMed Central

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. PMID:25894333

  11. Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas

    PubMed Central

    Zang, Xingxing; Sullivan, Peggy S; Soslow, Robert A; Waitz, Rebecca; Reuter, Victor E; Wilton, Andrew; Thaler, Howard T; Arul, Manonmani; Slovin, Susan F; Wei, Joyce; Spriggs, David R; Dupont, Jakob; Allison, James P

    2010-01-01

    B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3- and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P<0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P=0.02) and a higher incidence of recurrence (P=0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and

  12. Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility – Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours

    PubMed Central

    Findeklee, S.; Lotz, L.; Heusinger, K.; Hoffmann, I.; Dittrich, R.; Beckmann, M. W.

    2016-01-01

    Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours. PMID:27904170

  13. Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility - Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours.

    PubMed

    Findeklee, S; Lotz, L; Heusinger, K; Hoffmann, I; Dittrich, R; Beckmann, M W

    2016-11-01

    Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours.

  14. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health Professional Version Key Points ...

  15. Endocervical adenocarcinomas with ovarian metastases: analysis of 29 cases with emphasis on minimally invasive cervical tumors and the ability of the metastases to simulate primary ovarian neoplasms.

    PubMed

    Ronnett, Brigitte M; Yemelyanova, Anna V; Vang, Russell; Gilks, C Blake; Miller, Dianne; Gravitt, Patti E; Kurman, Robert J

    2008-12-01

    Most endocervical adenocarcinomas ( approximately 90%) are high-risk human papillomavirus (HPV)-related neoplasms, with the remainder being unrelated to HPV; both types infrequently metastasize to the ovaries. Clinicopathologic features of 29 cases of synchronous and metachronous endocervical and ovarian tumors (26 HPV-related, 3 unrelated to HPV) were analyzed. In 18 cases, the cervical tumors were clearly invasive; these included 5 clinically evident tumors diagnosed before the ovarian metastases (immediately preoperatively to 7 y), 11 clinically unsuspected tumors diagnosed concurrently in specimens obtained for evaluation of ovarian/pelvic masses, 1 case with concurrent clinically evident cervical and ovarian masses, and 1 clinically occult tumor diagnosed subsequent to the ovarian metastasis. In 11 cases, the cervical tumors were more limited; these included 5 tumors comprised predominantly of adenocarcinoma in situ with small foci of superficial invasion ("microinvasive carcinomas") diagnosed before the ovarian metastases (3 mo to 7 y) and 6 tumors comprised of extensive adenocarcinoma in situ lacking unequivocally recognizable stromal invasion diagnosed before (9 mo to 7 y, n=4), concurrently with (n=1), or subsequent to (n=1) the ovarian metastases. Fifteen cervical tumors involved lower uterine segment corpus endometrium or endomyometrium, including 4 tumors that were minimally invasive or not recognizably invasive in the cervix. The ovarian tumors ranged in size from 2.1 to 30.0 cm (mean/median=12.7/13.5); they were unilateral in 19 cases (65.5%) and 12 of these were unilateral and 10 cm or greater. In 26 cases, including the 19 unilateral tumors, the ovarian tumors exhibited "borderlinelike," confluent glandular, cribriform, and/or villoglandular patterns simulating primary ovarian atypical proliferative (borderline) tumors or well-differentiated carcinomas; these patterns were pure in 24 and admixed with minor infiltrative foci in 2. The ovarian tumors

  16. Ovarian tumor-derived ectopic hyperprolactinemia.

    PubMed

    Elms, Autumn F; Carlan, S J; Rich, Amy E; Cerezo, Lizardo

    2012-12-01

    To describe extreme hyperprolactinemia originating from a pituitary adenoma in the wall of an ovarian dermoid. This is a description of an unusual case and a review of ectopic prolactin production. Ectopic production of prolactin is a rare condition that has been reported in isolated organ system pathology including ovaries. An ovarian dermoid is a benign neoplasm that has the potential for active unregulated endocrine function. Hyperprolactinemia can result from functioning lactotrophs found in ovarian dermoids and can lead to clinical sequelae. Definitive treatment of the condition requires surgical removal of the functioning endocrine tissue. Extreme hyperprolactinemia caused by a pituitary tumor located within a dermoid has not been reported before. We present a case of profound hyperprolactinemia originating from a pituitary adenoma found in the wall of an ovarian dermoid and give a broad overview of the condition and literature. Ectopic prolactin production should always be considered in symptomatic patients found to have elevated serum levels and no findings on brain imaging.

  17. Mucinous Cystic Borderline Tumor of the Mesentery: A Case Report.

    PubMed

    Poudel, R; Acharya, A; Pokhrel, S; Adhikari, S K

    2015-01-01

    Mucinous cystic neoplasms are rare tumors of uncertain histogenesis. They arise from the ovaries, pancreas, and other intra-abdominal sites but more unusually from the mesentery. They can present with abdominal pain, distension, or a palpable mass but are commonly an incidental finding. We present a case of a 33-year-old female who presented with complain of pain abdomen for one-year duration. On Physical examination there was a palpable lump in right lumbar region extending to right iliac fossa. CT scan of abdomen and pelvis suggested the mass to be a Mesenteric Cyst. Enucleation of the cyst was done and histopathology report revealed Mucinous Cystic borderline tumor of the Mesentery.

  18. Ovarian tumor characterization using 3D ultrasound.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Krishnan, M Muthu Rama; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-12-01

    Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Preoperative determination of whether a tumor is benign or malignant has often been found to be difficult. Because of such inconclusive findings from ultrasound images and other tests, many patients with benign conditions have been offered unnecessary surgeries thereby increasing patient anxiety and healthcare cost. The key objective of our work is to develop an adjunct Computer Aided Diagnostic (CAD) technique that uses ultrasound images of the ovary and image mining algorithms to accurately classify benign and malignant ovarian tumor images. In this algorithm, we extract texture features based on Local Binary Patterns (LBP) and Laws Texture Energy (LTE) and use them to build and train a Support Vector Machine (SVM) classifier. Our technique was validated using 1000 benign and 1000 malignant images, and we obtained a high accuracy of 99.9% using a SVM classifier with a Radial Basis Function (RBF) kernel. The high accuracy can be attributed to the determination of the novel combination of the 16 texture based features that quantify the subtle changes in the images belonging to both classes. The proposed algorithm has the following characteristics: cost-effectiveness, complete automation, easy deployment, and good end-user comprehensibility. We have also developed a novel integrated index, Ovarian Cancer Index (OCI), which is a combination of the texture features, to present the physicians with a more transparent adjunct technique for ovarian tumor classification.

  19. Comparison of loss of heterozygosity patterns between ovarian tumors of low malignant potential and malignant ovarian tumors

    SciTech Connect

    Crawford, E.C.; Miller, D.M.; Finley, W.H.

    1994-09-01

    Ovarian tumors of low malignant potential (LMP) represent a pathologic subtype of ovarian tumor that possess many features common to malignant tumors including epithelial stratification, increased mitotic activity and atypical cellularity. These tumors, however, do not invade the ovarian stroma and have a much improved patient prognosis. Utilizing dinucleotide repeats, loss of heterozygosity (LOH) studies were performed on a total of 12 ovarian tumors of LMP in 5 regions found to have significant levels of LOH in malignant ovarian tumors. The regions chosen for study were 3p, 6q, 11p, 17p and 17q. LOH could be demonstrated in malignant ovarian tumors in loci from 3p, 11p and both chromosomal arms of 17 when compared to normal tissue from the same patient. Loss in malignant tumors was more common in loci mapped to 3p21 and to 11p15. OH was not noted in any samples for a repeat in the TP53 gene even though flanking markers on 17p were lost in 1 patient with a malignant tumor. Loss was not demonstrated in any of the loci examined from 6q in malignant ovarian tumors. LOH was not demonstrated in any of the 39 loci examined from any of the five chromosomal regions in the ovarian tumors of LMP. Cytogenetic analyses of these LMP tumors were consistent with lack of involvement in these chromosomal regions. These data suggest the mechanism of tumorigenesis is different in tumors of LMP from that in malignant ovarian tumors.

  20. Ovarian-Sparing Surgery in Pediatric Benign Ovarian Tumors.

    PubMed

    Abbas, Paulette I; Dietrich, Jennifer E; Francis, Jessica A; Brandt, Mary L; Cass, Darrell L; Lopez, Monica E

    2016-10-01

    To evaluate outcomes of children after ovarian-sparing surgery (OSS) for non-neoplastic and benign neoplastic ovarian lesions. Retrospective cohort study from January 2003 to January 2012. Single, high-volume, tertiary care hospital. Children 18 years of age and younger. None. Postoperative complications and tumor recurrence after OSS. One hundred nine patients underwent OSS with a median age of 13.3 years (interquartile range [IQR], 11.4-15.1 years). Eighty-two patients were treated laparoscopically with 4 conversions to an open procedure. Postoperative complications included surgical site infections in 7 patients (6%). Pathology most commonly revealed functional ovarian cysts (n = 57) and mature teratomas (n = 37). Ninety-four patients (86%) were followed for a median of 10.4 months (IQR, 0.72-30.8 months). Fifty-five patients (60%) had subsequent imaging surveillance a median of 7.6 months postoperatively (IQR, 3.9-13 months). Ten patients (10%) developed a second ipsilateral lesion within a median time of 11 months (IQR, 7.7-24 months), of whom 5 girls had repeated surgery for mass enlargement or persistent abdominal pain at a median time of 10.5 months (IQR, 8.0-12.65 months). Fifty-eight patients (63%) began or resumed menses at their most recent follow-up. Three girls became pregnant after OSS at a median follow-up of 5 years (range, 2.4-6.7 years). Benign ovarian lesions in children can be treated successfully with OSS with low recurrence and repeat surgery rates. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  1. Fertility Drug Use and the Risk of Ovarian Tumors in Infertile Women: A Case-Control Study

    PubMed Central

    Asante, Albert; Leonard, Phoebe H; Weaver, Amy L; Goode, Ellen L; Jensen, Jani R; Stewart, Elizabeth A; Coddington, Charles C

    2013-01-01

    Objective To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Design Case-control study (Mayo Clinic Ovarian Cancer Study). Setting Ongoing academic study of ovarian cancer. Patient(s) A total of 1900 women (1028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. Intervention(s) None Main outcome measure(s) Effect of infertility history, use of fertility drugs and oral contraception and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Result(s) Among women who had a history of infertility, use of fertility drugs was reported by 24% (44/182) of controls and 17% (38/226) of cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared to infertile women who did not use fertility drugs, adjusted odds ratio was 0.64 (95% CI 0.37, 1.11). Findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. Conclusion(s) We did not find any significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. PMID:23552324

  2. Classification of serous ovarian tumors based on microarray data using multicategory support vector machines.

    PubMed

    Park, Jee Soo; Choi, Soo Beom; Chung, Jai Won; Kim, Sung Woo; Kim, Deok Won

    2014-01-01

    Ovarian cancer, the most fatal of reproductive cancers, is the fifth leading cause of death in women in the United States. Serous borderline ovarian tumors (SBOTs) are considered to be earlier or less malignant forms of serous ovarian carcinomas (SOCs). SBOTs are asymptomatic and progression to advanced stages is common. Using DNA microarray technology, we designed multicategory classification models to discriminate ovarian cancer subclasses. To develop multicategory classification models with optimal parameters and features, we systematically evaluated three machine learning algorithms and three feature selection methods using five-fold cross validation and a grid search. The study included 22 subjects with normal ovarian surface epithelial cells, 12 with SBOTs, and 79 with SOCs according to microarray data with 54,675 probe sets obtained from the National Center for Biotechnology Information gene expression omnibus repository. Application of the optimal model of support vector machines one-versus-rest with signal-to-noise as a feature selection method gave an accuracy of 97.3%, relative classifier information of 0.916, and a kappa index of 0.941. In addition, 5 features, including the expression of putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and SOC groups. An accurate diagnosis of ovarian tumor subclasses by application of multicategory machine learning would be cost-effective and simple to perform, and would ensure more effective subclass-targeted therapy.

  3. Tumor vascular proteins as biomarkers in ovarian cancer.

    PubMed

    Buckanovich, Ronald J; Sasaroli, Dimitra; O'Brien-Jenkins, Anne; Botbyl, Jeffrey; Hammond, Rachel; Katsaros, Dionysios; Sandaltzopoulos, Raphael; Liotta, Lance A; Gimotty, Phyllis A; Coukos, George

    2007-03-01

    This study aimed to identify novel ovarian cancer biomarkers and potential therapeutic targets through molecular analysis of tumor vascular cells. Immunohistochemistry-guided laser-capture microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between vascular cells from human epithelial ovarian cancer and healthy ovaries. Tumor vascular markers (TVMs) were validated through quantitative real-time polymerase chain reaction (qRT-PCR) of immunopurified tumor endothelial cells, in situ hybridization, immunohistochemistry, and Western blot analysis. TVM expression in tumors and noncancerous tissues was assessed by qRT-PCR and was profiled using gene expression data. We identified a tumor vascular cell profile of ovarian cancer that was distinct from the vascular profile of normal ovary and other tumors. We validated 12 novel ovarian TVMs. These were expressed by immunopurified tumor endothelial cells and localized to tumor vasculature. Select TVMs were found to be specifically expressed in ovarian cancer and were absent in all normal tissues tested, including female reproductive tissues with physiologic angiogenesis. Many ovarian TVMs were expressed by a variety of other solid tumors. Finally, overexpression of any one of three ovarian TVMs by vascular cells was associated with decreased disease-free interval (all P < .005). We have identified for the first time the molecular profile of ovarian tumor vasculature. We demonstrate that TVMs may serve as potential biomarkers and molecular targets for ovarian cancer and a variety of other solid tumors.

  4. Ovarian hyperandrogenism and androgen-producing tumors.

    PubMed

    Lobo, R A

    1991-12-01

    The ovary is an active source of androgen secretion. This is regulated largely by LH but by insulin and other factors as well. Functional states include PCO as well as stromal hyperthecosis, which often mimics a neoplasm. Ovarian neoplasms are often gonadotropin responsive. Both functional and nonfunctional tumors may give rise to elevated androgen levels. Clinical history and the accurate assessment of testosterone measurements aid in the correct diagnosis of an androgen-secreting tumor. Imaging techniques, particularly vaginal ultrasound, are extremely valuable in making the diagnosis. Selective venous catheterization, although useful, should not be the primary diagnostic technique.

  5. Risk for borderline ovarian tumours after exposure to fertility drugs: results of a population-based cohort study.

    PubMed

    Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane; Jensen, Allan

    2015-01-01

    Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian tumours was observed after the use of progesterone. Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours, and the results are inconsistent. A retrospective case-cohort study was designed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963-2006. All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration, date of death or 31 December 2006, whichever occurred first. The median length of follow-up was 11.3 years. Included in the analyses were 142 women with borderline ovarian tumours (cases) and 1328 randomly selected sub-cohort members identified in the cohort during the follow-up through 2006. Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian tumours, overall and according to histological subtype, associated with the use of any fertility drug or five specific groups of fertility drugs: clomiphene citrate, gonadotrophins (human menopausal gonadotrophins and follicle

  6. [Frozen-section biopsy in ovarian neoplasm diagnosis: diagnostic correlation according to diameter and weight in tumors of epithelial origin].

    PubMed

    Cuello, M; Galleguillos, G; Zárate, C; Córdova, M; Brañes, J; Chuaqui, R; Wild, R

    1999-10-01

    Adequate management and treatment of ovarian carcinoma requires a complete surgical staging supported by frozen-section examination. To achieve this goal it is necessary a high level of accuracy. To evaluate the accuracy of frozen-sections in ovarian carcinoma considering the influence of tumor diameter and weight. Retrospective study of frozen-sections performed in patients with ovarian tumors who underwent surgery. Frozen- and permanent-sections were divided into three categories (benign, borderline and malignant) and stratified by diameter (< 10 cm, 10 to 20 cm, > 20 cm) and weight (< 700 g, 700 a 1400 g, > 1400 g). The diagnostic correlation, sensitivity, specificity, predictive values and accuracy of each frozen-section diagnosis were determined. Eight hundred forty two ovarian tumors that underwent frozen-sections between January 1988 and October 1998 were studied. Final diagnosis was 86.7% benign, 2.7% low malignant potential (LMP) and 10.6% malignant. The diagnosis correlation between frozen- and permanent-sections was 98.2%. Misdiagnosis was in epithelial ovarian tumors, particularly in LMP tumors. Sensitivity, specificity, positive- and negative-predictive values and accuracy of the four hundred eighty nine epithelial tumor were 92.6%, 99.2%, 96.7%, 98.2% and 97.9%, respectively. Diagnostic correlation was higher in epithelial ovarian tumors with diameter < 10 cm (98.2% v/s 93.8%) and weight < 700 g (96.9% v/s 88.9%). Diagnostic correlation with permanent-section examination, sensitivity, specificity and predictive values of frozen-sections are high in ovarian tumors. Accurate diagnosis at frozen sections of epithelial ovarian tumors with diameter > 10 cm or weight > 700 g (particularly in LMP tumors) is difficult because of the extensive sampling required. Frozen-sections diagnoses are important to determine the type and extent of surgery performed at the initial operation.

  7. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  8. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    PubMed Central

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  9. Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer.

    PubMed

    Nguyen, Thi My Hien; Shin, In-Whoan; Lee, Tae Jin; Park, Junsoo; Kim, Jae Hyung; Park, Mi Sun; Lee, Eun-Ju

    2016-03-01

    Integral membrane protein 2A (ITM2A) is a type 2 transmembrane protein of unknown function. The aim of this study was to investigate its expression pattern, clinical significance, and biological function in epithelial ovarian cancer. ITM2A expression in 35 normal, 20 adenoma, 11 borderline and 90 cancerous ovarian tissues was measured by immunohistochemistry. Clinicopathological parameters were obtained from medical records. Survival data was analyzed using Kaplan-Meier estimates and multivariate analysis using the Cox-regression method. Anti-tumor activities of ITM2A were explored by cell proliferation and colony formation assays, flow cytometry, Western blots and animal studies using ovarian cancer cell lines. Chemoresponsiveness was evaluated by measuring IC50 and confirmed by animal studies using an intraperitoneal orthotropic model. ITM2A was significantly downregulated in invasive carcinomas compared to normal, adenoma and borderline tumor tissues. ITM2A loss occurred in 45.6% (41 of 90) of invasive carcinomas and was significantly associated with FIGO stage, type II tumors, suboptimal debulking operation, recurrence and chemoresistance. ITM2A loss and higher FIGO stage were independent factors for poor prognosis. Expression of ITM2A inhibited growth and induced G2/M cell cycle arrest by attenuating cdc2, cyclin B1, cdc25c and p-cdc2 (Thr 161). In vitro and in vivo experiments showed that ITM2A expression significantly reduced the paclitaxel and carboplatin IC50 and tumor mass after paclitaxel treatment. ITM2A is a new biomarker of poor prognosis in ovarian cancer. It is a novel tumor suppressor that induces cell cycle arrest, acts as a chemosensitizer, and has therapeutic potential for ovarian cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous melanocytic tumors with malignant potential and normal cytogenetics.

    PubMed

    Magro, Cynthia M; Abraham, Ronnie M; Guo, Ruifeng; Li, Shibo; Wang, Xuan; Proper, Steven; Crowson, A Neil; Mihm, Martin

    2014-01-01

    Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained, along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the progressed melanoma. DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data.

  11. ATR-FTIR spectroscopy coupled with chemometric analysis discriminates normal, borderline and malignant ovarian tissue: classifying subtypes of human cancer.

    PubMed

    Theophilou, Georgios; Lima, Kássio M G; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Martin, Francis L

    2016-01-21

    Surgical management of ovarian tumours largely depends on their histo-pathological diagnosis. Currently, screening for ovarian malignancy with tumour markers in conjunction with radiological investigations has a low specificity for discriminating benign from malignant tumours. Also, pre-operative biopsy of ovarian masses increases the risk of intra-peritoneal dissemination of malignancy. Intra-operative frozen section, although sufficiently accurate in differentiating tumours according to their histological type, increases operation times. This results in increased surgery-related risks to the patient and additional burden to resource allocation. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, combined with chemometric analysis can be applied to discriminate between normal, borderline and malignant ovarian tumours and classify ovarian carcinoma subtypes according to the unique spectral signatures of their molecular composition. Formalin-fixed, paraffin-embedded ovarian tissue blocks were de-waxed, mounted on Low-E slides and desiccated before being analysed using ATR-FTIR spectroscopy. Chemometric analysis in the form of principal component analysis (PCA), successive projection algorithm (SPA) and genetic algorithm (GA), followed by linear discriminant analysis (LDA) of the obtained spectra revealed clear segregation between benign versus borderline versus malignant tumours as well as segregation between different histological tumour subtypes, when these approaches are used in combination. ATR-FTIR spectroscopy coupled with chemometric analysis has the potential to provide a novel diagnostic approach in the accurate diagnosis of ovarian tumours assisting surgical decision making to avoid under-treatment or over-treatment, with minimal impact to the patient.

  12. Ovarian Hormones and Borderline Personality Disorder Features: Preliminary Evidence for Interactive Effects of Estradiol and Progesterone

    PubMed Central

    Eisenlohr-Moul, Tory A.; DeWall, C. Nathan; Girdler, Susan S.; Segerstrom, Suzanne C.

    2015-01-01

    Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) predict emotions, cognitive processes, and behaviors relevant to Borderline Personality Disorder (BPD); however, there are individual differences in sensitivity to normal hormone shifts. This study examined associations of naturally occurring hormonal changes with concurrent BPD feature expression. Forty women sampled for a flat distribution of the PAI-BOR (n=10 where T<50, n=10 where 5070) provided 4 weekly saliva samples and psychological assessments. Across most outcomes (e.g., BPD features, felt rejection, anger rumination, negative urgency) P4 deviation (from one’s person mean) moderated the effect of current E2 deviation (from one’s person mean) among women high (+1 SD) in trait BPD features such that E2 deviation was negatively associated with symptoms only when P4 was higher-than-usual. Cyclical hormone changes (e.g., higher P4 in the luteal phase; E2 fluctuations at ovulation and in the luteal phase) may impact BPD feature expression among at-risk women. PMID:25837710

  13. Nomogram to predict live birth rate after fertility-sparing surgery for borderline ovarian tumours.

    PubMed

    Ouldamer, L; Bendifallah, S; Naoura, I; Body, G; Uzan, C; Morice, P; Ballester, M; Daraï, E

    2016-08-01

    Can a nomogram be used to predict the individual probability of live birth (LB) in women with borderline ovarian tumours (BOTs) receiving primary fertility-sparing surgery? A nomogram built according to the woman's age, histological subtype (serous versus mucinous), type of ovarian surgical treatment and FIGO stage can accurately predict the probability of LB in women with BOT. Current prediction models determine the probability of pregnancy after medically assisted reproduction (MAR) and form the basis of patient counselling to guide the decision as to whether to consider in vitro fertilization but do not take into account prediction of the LB rate. This was a retrospective multi-centre study including 187 women with fertility-sparing surgery for BOT diagnosed between January 1980 and December 2013. A multivariate logistic regression analysis of selected factors and a nomogram to predict the subsequent LB rate was constructed. A bootstrapping technique was used for internal validation. Fifty-one women had LB (27.3%). Taking into account multiple pregnancies, the overall LB rate was 40.1% (75/187). Federation International of Gynaecology and Obstetric (FIGO) stage, age at diagnosis, histological subtype and surgery type were included in the nomogram. The predictive model had an AUC of 0.742 (95% CI, 0.644-0.825) and 0.72 (95% CI, 0.621-0.805) before and after the 200 repetitions of bootstrap sample corrections, respectively, and showed a good calibration. The retrospective nature of the study cannot exclude all biases. Our nomogram is based on simple criteria, but did not take into account the evaluation of ovarian reserve. It demonstrates a fair relevance, but requires external validation before routine use. Clinicians are increasingly interested in such tools to support the patient in making an informed decision about treatment options. This nomogram contributes to the decision-making by defining simple risk factors of poor LB probability that can help identify

  14. The status of epidermal growth factor receptor in borderline ovarian tumours

    PubMed Central

    Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona

    2016-01-01

    The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear

  15. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    PubMed

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy. © 2015 UICC.

  16. Mitochondrial DNA Mutations in Epithelial Ovarian Tumor Progression

    DTIC Science & Technology

    2007-12-01

    histological subtype of ovarian cancer and is the most lethal gynecologic malignancy. The relationship between stage at presentation and survival in serous ...among and within stages of epithelial ovarian cancer , focusing on serous , mucinous and endometrioid subtypes (1-18 Months). a. Collections and...not serous or mucinous epithelial ovarian tumors. Cancer Res 58: 2095-2097, 1998. 7. Aikhionbare FO et al:.: Is cumulative frequency of mitochondrial

  17. A rare ovarian tumor, leydig stromal cell tumor, presenting with virilization: a case report

    PubMed Central

    Aminimoghaddam, Soheila; Hashemi, Forough

    2012-01-01

    Leydig stromal cell tumor is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. They produce testosterone leading to hyperandrogenism. We present a 41yr old woman with symptoms of virilization and a mass of right adenex via ultra Sonography, and a rise of total and free serum testosterone. An ovarian source of androgen was suspected and a surgery performed. A diagnosis of leydig-stromal cell tumor was confirmed. Our report is a reminder that although idiopathic hirsutism and other benign androgen excess disorder like Polycystic Ovarian Syndrome (PCOs) are common, ovarian mass should be considered in differential diagnosis. PMID:23482693

  18. Comparison of clinical characteristics between benign borderline and malignant phyllodes tumors of the breast.

    PubMed

    Wang, Hui; Wang, Xiang; Wang, Cheng-Feng

    2014-01-01

    Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known about this disease entity. The present study was designed to identify differences in clinical features between benign borderline and malignant phyllodes tumors. Data from 246 women with phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012 were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor, location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenoma history, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant tumors. In univariate analysis, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number of mitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003, <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statistically significant variation (p=0.400, 0.286 and 0.413, respectively). Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize.

  19. Intraoperative Diagnosis Support Tool for Serous Ovarian Tumors Based on Microarray Data Using Multicategory Machine Learning.

    PubMed

    Park, Jee Soo; Choi, Soo Beom; Kim, Hee Jung; Cho, Nam Hoon; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji; Chung, Jai Won; Kim, Deok Won

    2016-01-01

    Serous borderline ovarian tumors (SBOTs) are a subtype of serous ovarian carcinoma with atypical proliferation. Frozen-section diagnosis has been used as an intraoperative diagnosis tool in supporting the fertility-sparing surgery by diagnosing SBOTs with accuracy of 48% to 79%. Using DNA microarray technology, we designed multicategory classification models to support frozen-section diagnosis within 30 minutes. We systematically evaluated 6 machine learning algorithms and 3 feature selection methods using 5-fold cross-validation and a grid search on microarray data obtained from the National Center for Biotechnology Information. To validate the models and selected biomarkers, expression profiles were analyzed in tissue samples obtained from the Yonsei University College of Medicine. The best accuracy of the optimal machine learning model was 97.3%. In addition, 5 features, including the expression of the putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and serous ovarian carcinoma groups. Different expression levels of SNTN and AOX1 were validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. A multinomial logistic regression model using SNTN and AOX1 alone was used to construct a simple-to-use equation that gave a diagnostic test accuracy of 91.9%. We identified 2 biomarkers, SNTN and AOX1, that are likely involved in the pathogenesis and progression of ovarian tumors. An accurate diagnosis of ovarian tumor subclasses by application of the equation in conjunction with expression analysis of SNTN and AOX1 would offer a new accurate diagnosis tool in conjunction with frozen-section diagnosis within 30 minutes.

  20. Endometriosis-associated serous borderline tumor and endometrial stromal sarcoma of the ovary: a report of a rare lesion in an infant.

    PubMed

    Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C

    2012-01-01

    Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.

  1. LL-37 Recruits Immunosuppressive Regulatory T Cells to Ovarian Tumors

    DTIC Science & Technology

    2009-11-01

    infiltration. Further, these studies showed that MSCs are recruited to the ovarian tumors via engagement of their LL-37 receptor formyl receptor-like 1...increased leukocyte infiltration. Further, these studies showed that MSCs are recruited to the ovarian tumors via engagement of their LL-37 receptor formyl ...2009 Jun 2. Presentations One poster “The role of human cationic antimicrobial protein 18 (hCAP-18), its derivative LL-37, and its receptor formyl

  2. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2012-06-01

    blocks apoptosis induced by the mammalian lectin, galectin - 3 , which our studies show is expressed in human ovarian tumor tissues and in ascitic fluid...omental cultures. • Optimized immunoblotting protocol for galectin - 3 in ascites • Determination that sialylation of Fas and TNFR1 blocks apoptotic...REPORT DATE 2. REPORT TYPE Annual report 3 . DATES COVERED 4. TITLE AND SUBTITLE Role of receptor sialylation in the ovarian tumor cell

  3. Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

    PubMed

    Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

    2016-07-01

    The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    ClinicalTrials.gov

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  5. Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B.

    PubMed

    Czekierdowska, Sylwia; Stachowicz, Norbert; Chróściel, Mieczysław; Czekierdowski, Artur

    2017-01-01

    Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors. Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin. Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12-31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microves-sels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses. We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed.

  6. CT and MR findings of Krukenberg tumors: Comparison with primary ovarian tumors

    SciTech Connect

    Kim, Seung Hyup; Kim, Won Hong; Park, Kyung Joo

    1996-05-01

    The purposes of this study were to evaluate the CT and MR findings of Krukenberg tumors and to compare them with those of primary ovarian tumors. This study included 20 patients with Krukenberg tumors and 65 patients with various primary ovarian tumors. CT/MR/both imaging studies were available in 15/1/4 patients with Krukenberg tumor and 31/10/24 patients with primary ovarian tumors, respectively. Imaging findings of the tumors were categorized into three subgroups: a solid mass with intratumoral cysts, a solid mass without intratumoral cysts, and a predominantly cystic mass. Among 32 Krukenberg tumors (bilateral in 12 patients), 22 were solid masses with intratumoral cysts, in 14 of which the wall of the intratumoral cysts showed apparently strong contrast enhancement on CT and/or MRI. Six Krukenberg tumors were solid masses without intratumoral cysts, and four were predominantly cystic masses. Imaging findings of 88 primary ovarian tumors (bilateral in 23 patients) were 5 solid masses with intratumoral cysts, 27 solid masses without intratumoral cysts, and 56 predominantly cystic masses. None of the five primary ovarian tumors with solid mass with intratumoral cysts demonstrated apparently strong contrast enhancement of the cyst wall. Krukenberg tumor should be suspected when one sees solid ovarian tumors containing well demarcated intratumoral cystic lesions, especially if the walls of those cysts demonstrate apparently strong contrast enhancement. 11 refs., 4 figs., 1 tab.

  7. Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

    PubMed

    Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

    2017-01-01

    Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

  8. Regulatory T lymphocytes and transforming growth factor beta in epithelial ovarian tumors-prognostic significance.

    PubMed

    Winkler, Izabela; Wilczynska, Barbara; Bojarska-Junak, Agnieszka; Gogacz, Marek; Adamiak, Aneta; Postawski, Krzysztof; Darmochwal-Kolarz, Dorota; Rechberger, Tomasz; Tabarkiewicz, Jacek

    2015-06-17

    Regulatory T lymphocytes (Treg) are characterized by the presence of CD4+ surface antigen. Today the transcription factor FOXP3 is considered to be the most specific marker of Treg cells. The aim of the study was to estimate the percentage of Treg in peripheral blood and the tissue of the epithelial ovarian tumor and blood serum TGF-beta concentrations and relationships between them. Moreover, the aim of the study was to answer the question whether the percentage of Treg lymphocytes affects the time of survival in patients with ovarian cancer. The patients were divided into four groups, depending on the histopathological examination result: I--a group without any pathology within the ovaries (C; n = 20), II--a group with benign tumors (B; n = 25), III - with borderline tumors (BR; n = 11), IV--a group with cancer of the ovary (M; n = 24). The percentage of Treg lymphocytes in peripheral blood and the tissue was assessed using the flow cytometry method. TGF-beta cytokine concentration was estimated with the ELISA immunoenzymatic test. Statistical analysis of the results was conducted using the computer program Statistica 10.0PL (StatSoft, Inc). No significant differences were found in percentages of Treg lymphocytes in peripheral blood between individual groups of patients (p = 0.11). However, we observed marked differences in the tissue of malignant and non-malignant tumors between individual groups of patients (p = 0.003). The analysis with the post hoc test revealed significantly higher TGF-beta concentration in the group of women with malignant tumors. Moreover, no relationship was found between TGF-beta concentration and the percentage of Treg cells in peripheral blood and tumors of the ovary. No correlation was found between the percentage of Treg lymphocytes in peripheral blood (p = 0.4) and the tissue of ovarian tumors (p = 0.3) and the time of survival of patients with ovarian cancer. The recruitment of Treg lymphocytes

  9. Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-04-05

    Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

  10. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

    PubMed Central

    Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

    2015-01-01

    Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

  11. Cadherin-11 mRNA and protein expression in ovarian tumors of different malignancy: No evidence of oncogenic or tumor-suppressive function

    PubMed Central

    VON BÜLOW, CHARLOTTE; OLIVEIRA-FERRER, LETICIA; LÖNING, THOMAS; TRILLSCH, FABIAN; MAHNER, SVEN; MILDE-LANGOSCH, KARIN

    2015-01-01

    Cadherin-11 (CDH11, OB-cadherin) is a mesenchymal cadherin found to be upregulated in various types of tumors and implicated in tumor progression and metastasis. In order to determine the role of CDH11 expression in ovarian tumors, we performed a combined reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical study on a large cohort of benign, borderline and invasive ovarian tumors. The RT-qPCR and western blot analysis demonstrated that the CDH11 expression was high in benign cystadenomas and decreased with increasing malignancy. This may be explained by the different tumor-stroma ratios, since immunohistochemistry revealed strong staining of stromal cells, particularly vascular smooth muscle cells and endothelial cells, but only weak cytoplasmic or nuclear immunoreactivity of cancer cells. Within the group of invasive carcinomas, high CDH11 protein expression, as detected by western blot analysis, was found to be significantly correlated with advanced stage and nodal involvement. However, the recurrence-free and overall survival analyses did not reveal any prognostic or predictive significance. In conclusion, in contrast to other tumor types, CDH11 does not play an important role in ovarian cancer progression. PMID:26623052

  12. Pediatric ovarian tumors: a review of 67 cases.

    PubMed

    Schultz, Kris Ann P; Sencer, Susan F; Messinger, Yoav; Neglia, Joseph P; Steiner, Marie E

    2005-02-01

    Ovarian tumors are uncommon but important childhood neoplasms. We reviewed records of 67 pediatric patients presenting to three pediatric referral centers from 1980 to 2003. Thirty patients had benign tumors. Thirty-seven patients had malignant tumors: 11 immature teratomas, seven malignant mixed germ cell tumors, seven juvenile granulosa cell tumors, five dysgerminomas, two endodermal sinus tumors, two serous papillary cystadenocarcinomas, one small cell carcinoma, one anaplastic sex-cord tumor, and one undifferentiated sarcoma. More than half presented with abdominal pain. Forty-six percent had an abdominal mass at the time of presentation. Other signs and symptoms included poor appetite (15%), urinary symptoms/urinary infection (9%), menstrual changes (9%), and weight loss (6%). Precocious puberty was noted in seven patients. Torsion was seen more often in patients with benign tumors (23 vs. 8%); two patients had both torsion and acute appendicitis. The neoplasm was an incidental finding in 12 patients. Fifty-five percent of the 67 ovarian tumors presenting to our centers were malignant. Pain was the most common symptom, although presence of an abdominal mass was frequent, and other symptoms non-specific. Almost all neoplasms presented as unilateral masses and rarely were metastatic at diagnosis. Ovarian tumors must be considered in the differential diagnosis of young girls with abdominal pain, mass, or other non-specific symptoms.

  13. Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

    PubMed Central

    Penet, Marie-France; Krishnamachary, Balaji; Wildes, Flonne; Mironchik, Yelena; Mezzanzanica, Delia; Podo, Franca; de Reggi, Max; Gharib, Bouchra; Bhujwalla, Zaver M.

    2016-01-01

    Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm3 and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action. PMID:27900284

  14. Serous borderline tumor of the fallopian tube in a patient with Klippel-Trenaunay syndrome.

    PubMed

    Stephens, Daniel; Pillai, Srikumar; Cham, Elaine; Arensman, Robert; Chou, Pauline

    2010-11-01

    We describe a case of a 3-year-old girl with Klippel-Trenaunay syndrome who presented with an enlarging abdominal mass caused by a serous borderline tumor of the fallopian tube. This case is notable for the rarity of this neoplasm in a premenarchal patient as well as the association with this syndrome. We briefly review these entities and the significance of malignancy in Klippel-Trenaunay syndrome. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

    DTIC Science & Technology

    2016-05-01

    1 AWARD NUMBER: W81XWH-15-1-0082 TITLE: A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development PRINCIPAL INVESTIGATOR: Qinglei Li...5a. CONTRACT NUMBER A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development 5b. GRANT NUMBER W81XWH-15-1-0082 5c. PROGRAM ELEMENT NUMBER 6...role of sustained activation of oocyte TGFBR1 in ovarian tumor development using an in vitro approach. 2. Keywords Ovarian tumor, Sex cord

  16. Ovarian Tumor Cells Studied Aboard the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    2001-01-01

    In August 2001, principal investigator Jeanne Becker sent human ovarian tumor cells to the International Space Station (ISS) aboard the STS-105 mission. The tumor cells were cultured in microgravity for a 14 day growth period and were analyzed for changes in the rate of cell growth and synthesis of associated proteins. In addition, they were evaluated for the expression of several proteins that are the products of oncogenes, which cause the transformation of normal cells into cancer cells. This photo, which was taken by astronaut Frank Culbertson who conducted the experiment for Dr. Becker, shows two cell culture bags containing LN1 ovarian carcinoma cell cultures.

  17. Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism

    PubMed Central

    YUAN, LEI; LIU, XISHI

    2015-01-01

    Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti-estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet-depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO-injected group was increased significantly compared with the late TPO-injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer. PMID:25502723

  18. Ovarian germ cell tumors in children. Management, survival and ovarian prognosis. A report of 75 cases.

    PubMed

    Vaysse, Charlotte; Delsol, Martine; Carfagna, Luana; Bouali, Ourdia; Combelles, Sophie; Lemasson, Frederique; Le Mandat, Aurélie; Castex, Marie-Pierre; Pasquet, Marlène; Moscovici, Jacques; Guitard, Jacques; Pienkowski, Catherine; Rubie, Hervé; Galinier, Philippe; Vaysse, Philippe

    2010-07-01

    The aims of this study were to evaluate survival and ovarian prognosis in patients treated for ovarian germ cell tumor (OGCT) and to propose a decision-making protocol. Charts of girls operated on for OGCT from 1976 up to 2009 were reviewed retrospectively. Tumor characteristics were assessed by tumor markers, imaging, and pathology. Charts were available in 71 children presenting 75 OGCT. Tumors were benign in 58 cases and malignant in 17 cases. The average of the largest diameter of benign OGCT was significantly lower than that of malignant OGCT (76.5 +/- 49 mm versus 169 +/- 54 mm, P < .0001). Ovarian-sparing tumorectomy was carried out in 27 benign OGCT; 23 (85%) preserved ovaries were follicular. Malignant OGCTs were managed according to the protocols of the French Society for Pediatric Oncology. Bilateral oophorectomy had to be performed in 2 children. One patient presented a recurrence and 1 died. In our series, both benign and malignant OGCTs have a good prognosis. A 75-mm cutoff size is proposed as an important criterion to preoperatively differentiate between benign and malignant tumors. In benign OGCT, ovarian-sparing tumorectomy leads to preserve ovaries in approximately 85% of cases, and in malignant OGCT, high survival rate has been obtained. Copyright 2010 Elsevier Inc. All rights reserved.

  19. [Association between sonographic findings and histological diagnosis of 446 ovarian tumors].

    PubMed

    Franzin, Cleide Mara Mazzotti de Oliveira; Marussi, Emílio Francisco; Zeferino, Luiz Cralos; Sarian, Luís Otávio Zanatta; Prada, Mariana Fonseca

    2006-01-01

    The objective was to analyze the correlations between the sonographic features of the ovarian masses and the histological diagnosis. A retrospective study which involved 404 female subjects who had developed 446 ovarian masses was carried out. Patients who had been submitted to surgery due to uni or bilateral ovarian tumors were included and those presenting with an ectopic pregnancy or pelvic inflammatory process were excluded. Data from the patients' medical charts provided the information needed for a detailed study of the following variables: larger diameter, external borders and texture of the sonographic masses. This collected data was correlated to post surgery pathology diagnoses. The magnitude of the associations between pathology diagnoses and sonographic morphologic findings where estimated by the Odds Ratio with its respective confidence intervals of 95%. In their majority, masses were benign tumors (88.1%). Malign masses corresponded to 9.4 % of the total and only 2.5% were borderline. Patients' ages ranged from 13 to 63 years (with an average of 39.1). Regarding the irregular and poorly delimited borders of the masses, the odds ratio for malignancy was of 17.8. After analyses of the sonographic texture the odds ratio of complex texture masses proved to be extremely high (38.6). The anechoic masses with thickened septa had an odds ratio of 35.6, while that of the solid masses was of 15.5. Sonographic analyses of adnexal tumors having more than 7 cm of diameter, irregular and poorly delimited external borders, presenting complex or anechoic textures with thickened septa or solid mass are highly suggestive of malignancy.

  20. COTA (colon-ovarian tumor antigen). An immunohistochemical study.

    PubMed

    Pant, K D; Fenoglio-Preiser, C M; Berry, C O; Zamora, P O; Ram, M D; Fulks, R M; Rhodes, B A

    1986-07-01

    A goat anti-serum was prepared against mucinous ovarian cyst fluid and absorbed with normal colon and a variety of normal tissues until the only residual immunoreactivity was directed against colon cancer and ovarian tumor mucin. The set of antigenic determinants defined by this anti-serum has been called COTA, standing for colon-ovarian-tumor-antigen. This highly absorbed anti-serum (anti-COTA) was used for immunohistochemical staining of 42 different tissues in parallel with staining with a goat anti-CEA, which was also highly absorbed. The results suggest that COTA is a highly sensitive and specific antigen for colon carcinoma and may have potential for the early detection of malignant changes predictive of cancer of the colon.

  1. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast.

    PubMed

    Moutte, Amandine; Chopin, Nicolas; Faure, Christelle; Beurrier, Frédéric; Ho Quoc, Christophe; Guinaudeau, Florence; Treilleux, Isabelle; Carrabin, Nicolas

    2016-09-01

    Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. © 2016 Wiley Periodicals, Inc.

  2. Structural and Biochemical Studies of the Ovarian Tumor Domain

    DTIC Science & Technology

    2007-05-01

    for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14.ABSTRACT BRCA1, or Breast Cancer Associated gene 1, is a breast and...ovarian cancer -specific tumor suppressor. Recent research has shown that BRCA1, an E3 ubiquitin ligase, interacts in a complex that contains the human...16 4 INTRODUCTION BRCA1, or Breast Cancer

  3. Using Artificial Neural Networks to Predict Malignancy of Ovarian Tumors

    DTIC Science & Technology

    2007-11-02

    This paper discusses the application of artificial neural networks (ANNs) to preoperative discrimination between benign and malignant ovarian tumors...With the input variables selected by logistic regression analysis, two types of feed-forward neural networks were built: multi-layer perceptrons

  4. Bilateral Sclerosing Stromal Ovarian Tumor in an Adolescent

    PubMed Central

    Naidu, Anjani; Chung, Betty; Simon, Mitchell; Marshall, Ian

    2015-01-01

    Sclerosing stromal tumor of the ovary is a rare, benign, sex cord stromal tumor occurring predominantly in younger women in the 2nd and 3rd decades of life. It typically presents unilaterally with only 2 previously reported cases of bilateral presentation. Common clinical presentations include pelvic or abdominal pain, a mass, or menstrual changes. Although occasionally presenting with hormonal manifestations, virilization as a result of androgen production by the tumor is rare. Here we present an extremely rare case of a sclerosing stromal ovarian tumor in a 14-year-old patient with bilateral presentation and with clinical and biochemical evidence of hyperandrogenemia. PMID:26064755

  5. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

    PubMed Central

    Lazennec, Gwendal

    2006-01-01

    Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

  6. Ovarian-type epithelial tumours of the testis: immunohistochemical and molecular analysis of two serous borderline tumours of the testis.

    PubMed

    Bürger, Tobias; Schildhaus, Hans-Ulrich; Inniger, Reinhard; Hansen, Joachim; Mayer, Peter; Schweyer, Stefan; Radzun, Heinz Joachim; Ströbel, Philipp; Bremmer, Felix

    2015-07-22

    Tumours of ovarian-epithelial type of the testis, including serous borderline tumours, represent very rare entities. They are identical to the surface epithelial tumours of the ovary and have been reported in patients from 14 to 68 years of age. We describe two cases of a 46- and a 39-year old man with incidental findings of intratesticular masses of the left respectively right testis. Under the assumption of a malignant testicular tumour the patients were subjected to inguinal orchiectomy. Histologically, the tumours were identical to their ovarian counterparts: They showed a cystic configuration with a fibrous wall and irregular papillary structures lined by partially multistratified columnar cells and areas of hobnail cells. Furthermore, there was mild cytological atypia with a proliferative activity of below 5% as proved by Ki67 staining; mitoses could not be detected. Immunohistochemically, the tumour cells displayed expression of pan-cytokeratin AE3, progesterone receptor, Wilms' tumour protein (WT1), and PAX8 (Paired box gene 8). Estrogen receptor was expressed in one case. Octamer-binding transcription factor-4 (OCT4), calretinin, thrombomodulin, and D2-40 were not expressed. Mutation testing of BRAF revealed a BRAF V600E mutation in one case, while testing for KRAS mutations proved to be negative in both. The BRAF mutated tumour showed strong cytosolic and membranous positivity for B-Raf also on immunohistochemical analysis. Comparative genomic hybridization of one case could not reveal any chromosomal aberrations.

  7. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

    PubMed

    Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

    2015-02-17

    Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

  8. TUMOR PENETRATING MICROPARTICLES FOR INTRAPERITONEAL THERAPY OF OVARIAN CANCER

    PubMed Central

    Lu, Ze; Tsai, Max; Lu, Dan; Wang, Jie; Wientjes, M. Guillaume; Au, Jessie L.-S.

    2009-01-01

    Intraperitoneal (IP) chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous IP therapy used the paclitaxel/Cremophor formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for IP treatment (referred to as tumor penetrating microparticles or TPM). Evaluation of TPM was performed using IP metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming while the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of IP therapy. PMID:18780831

  9. Comparison of c-met Expression in Ovarian Epithelial Tumors and Normal Epithelia of the Female Reproductive Tract by Quantitative Laser Scan Microscopy

    PubMed Central

    Huntsman, David; Resau, James H.; Klineberg, Eric; Auersperg, Nelly

    1999-01-01

    The transmembrane tyrosine kinase receptor c-met with its ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia. HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis. In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis. Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9). Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4–12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4–4.3). In eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. PMID:10433927

  10. The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy

    DTIC Science & Technology

    2016-07-01

    dynamic process that involves critical interactions between tumor cells and the microenvironment . Hypoxia is a potent microenvironmental factor...AWARD NUMBER: W81XWH-15-1-0097 TITLE: The Role of Hypoxia in the Tumor Microenvironment : Implications for Ovarian Cancer Therapy PRINCIPAL... Microenvironment : Implications for Ovarian Cancer Therapy Ovarian Cancer Therapy 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  11. Epigenetic Regulation of Ovarian Tumor Immunity

    DTIC Science & Technology

    2010-11-01

    immunity PRINCIPAL INVESTIGATOR: Protul A. Shrikant, Ph.D. CONTRACTING ORGANIZATION : Health Research Inc., Roswell Park Cancer...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Roswell Park Cancer...intraperitoneal injection on day 10 post-tumor challenge. 2. The cells harvested from the tumor draining LN’s, spleen and the tumor site starting on day 2

  12. [MALIGNANT TUMORS IN OVARIAN MATURE CYSTIC TERATOMAS INTRAOPERATIVE DIAGNOSTIC BASIS].

    PubMed

    Khachatryan, A

    2016-11-01

    Extremely rare ovarian primary tumors formed in a mature cystic teratomaare described in the literature. This research work studies the frequency of malignant mature cystic teratoma, as well as their clinical and morphological features and necessity of intraoperative histological examination of all teratomas. Cases histories of 56 patients, suffering from ovarian mature cystic teratomahave been studied in MC Shengavit in the period of 2003 - 2015. Among them 4 patients with the somatic malignancies were identified. Morphological methods, which are considered to be "gold standard" of tumor investigation, were used in staining the slides with hematoxylin - eosin. According to the literature the secondary malignant transformation rarely occurs and is typical in postmenopausal women, with a frequency of 0.17-3%. According to the results of our study, malignant tumors in mature cystic teratomas were observed in 4 (7,14%) from the total number of mature cystic teratomas (n=56). There was not revealed a correlation between the duration of the complaints, age of the patients, sizes of ovarian mature teratoma and malignization degree. Thus, the greatest difficulties of clinical diagnosis of malignant tumors in the ovarian mature cystic teratomas were in the early stage of the disease, because of a variety of clinical manifestations, not pathognomonic for malignization. All mentioned symptoms may be observed in the patients with usual mature cystic teratomas. Тhis cases confirm the necessity to take tissue samples from the other ovary for intraoperative histopathological evaluation in each case of mature cystic teratomas. It is necessary to examine a large number of tumor sites, to prevent errors in the assessment of the maturity degree of teratoma.

  13. Associations between hormone receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

    PubMed Central

    Sieh, Weiva; Köbel, Martin; Longacre, Teri A.; Bowtell, David D.; deFazio, Anna; Goodman, Marc T.; Høgdall, Estrid; Deen, Suha; Wentzensen, Nicolas; Moysich, Kirsten B.; Brenton, James D.; Clarke, Blaise; Menon, Usha; Gilks, C. Blake; Kim, Andre; Madore, Jason; Fereday, Sian; George, Joshy; Galletta, Laura; Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Thompson, Pamela J.; Matsuno, Rayna K.; Kjær, Susanne Krüger; Jensen, Allan; Høgdall, Claus; Kalli, Kimberly R.; Fridley, Brooke L.; Keeney, Gary L.; Vierkant, Robert A.; Cunningham, Julie M.; Brinton, Louise A.; Yang, Hannah P.; Sherman, Mark E.; Garcia-Closas, Montserrat; Lissowska, Jolanta; Odunsi, Kunle; Morrison, Carl; Lele, Shashikant; Bshara, Wiam; Sucheston, Lara; Jimenez-Linan, Mercedes; Blows, Fiona M.; Alsop, Jennifer; Mack, Marie; McGuire, Valerie; Rothstein, Joseph H.; Rosen, Barry P.; Bernardini, Marcus Q.; Mackay, Helen; Oza, Amit; Wozniak, Eva L.; Benjamin, Elizabeth; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Tinker, Anna V.; Prentice, Leah M.; Chow, Christine; Anglesio, Michael S.; Johnatty, Sharon E.; Chenevix-Trench, Georgia; Whittemore, Alice S.; Pharoah, Paul D. P.; Goode, Ellen L.; Huntsman, David G.; Ramus, Susan J.

    2014-01-01

    Background Ovarian cancer is a lethal disease comprised of distinct histopathological types. There are few established biomarkers of ovarian cancer prognosis, in part because subtype-specific associations may have been obscured in studies combining all subtypes. We examined whether progesterone receptor (PR) and estrogen receptor (ER) protein expression were associated with subtype-specific survival in the international Ovarian Tumor Tissue Analysis (OTTA) consortium. Methods PR and ER were assessed by central immunohistochemical analysis of tissue microarrays for 2933 women with invasive epithelial ovarian cancer from 12 study sites. Negative, weak, and strong expression were defined as positive staining in <1%, 1–50%, and ≥50% of tumor cell nuclei, respectively. Hazard ratios (HRs) for ovarian cancer death were estimated using Cox regression stratified by site and adjusted for age, stage, and grade. Results PR expression was associated with improved survival for endometrioid (EC; p<0·0001) and high-grade serous carcinoma (HGSC; p=0·0006), and ER expression was associated with improved EC survival (p<0·0001); no significant associations were found for mucinous, clear cell, or low-grade serous carcinoma. EC patients with hormone receptor (PR and/or ER) positive (weak or strong) versus negative tumors had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·33; 95% CI, 0·21–0·51; p<0·0001). HGSC patients with strong versus weak or negative tumor PR expression had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·71; 95% CI, 0·55–0·91; p=0·0061). Interpretation PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to determine whether hormone receptor status predicts response to endocrine therapy, and can guide personalized treatment for ovarian cancer

  14. Surgical staging of early invasive epithelial ovarian tumors.

    PubMed

    Leblanc, E; Querleu, D; Narducci, F; Chauvet, M P; Chevalier, A; Lesoin, A; Vennin, P; Taieb, S

    2000-01-01

    Early stage epithelial ovarian carcinoma is defined pathologically as a tumor strictly limited to one or both ovaries without any extra-ovarian disease (i.e., Stage IA or B of the International Federation of Gynecology and Obstetrics (FIGO) classification). This diagnosis can be obtained only after an exhaustive surgical staging procedure, performed as soon as the diagnosis of epithelial invasive ovarian carcinoma is established. This staging surgery currently encompasses a peritoneal cytology, the thorough inspection of all the visceral and parietal peritoneal surfaces with biopsy of any abnormality, total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO), random peritoneal biopsies, omentectomy, appendectomy and bilateral pelvic and para-aortic lymphadenectomies, up to the left renal vein. The results of this staging procedure and its indications are discussed. In all of the cases, the radical removal of the pathologic adnexa is indicated, along with the complete peritoneal and retroperitoneal staging. While fertility-sparing surgery (avoiding hysterectomy and contralateral adnexectomy, if possible) seems to be safe for young women, a TAH + BSO is the rule for the others. Adjuvant chemotherapy can be omitted in well-differentiated tumors with a negative staging operation, but currently it remains indicated in all other cases. Indeed, the ultimate goal in early stage ovarian carcinoma is to not impair by inadequate management the high chance of a cure. Copyright 2000 Wiley-Liss, Inc.

  15. Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients.

    PubMed

    Ibrahim, Wael S

    2011-01-01

    Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. In the 24 cases of benign phyllodes tumors, only four cases (16.7%) showed positive CD10 reactivity. Three cases (60%) out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80%) out of five cases of malignant phyllodes tumors showed positive CD10 staining. From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.

  16. Evidence for ovarian tumor necrosis factor

    SciTech Connect

    Roby, K.F.

    1989-01-01

    Ovarian folliculogenesis and luteal formation occur concomitantly with the development of new blood vessels that function in nutritional support of the developing follicles. As follicles undergo atresia and the corpus luteum regresses, blood vessels supplying these tissues degenerate. The first study determined if the ovary contained factors that might regulate ovarian angiogenesis. The bovine ovary was subjected to ammonium sulfate (AS) precipitation and the precipitates (ppt.) were assayed in vitro for effects on endothelial cell (CPAE) and fibroblast (3T3 and L929) incorporation of {sup 3}H-thymidine. Heparin sepharose (HS) chromatography of the 80% AS ppt. revealed the inhibitory activity on CPAE and L929 cells did not bind to HS but was found in the HS column breakthrough (80% BT). Sizing chromatography of the 80% BT indicated thymidine incorporation inhibitory activity exhibited a molecular weight of 30,000-50,000 Daltons. TNF was immunohistochemically localized in the human, bovine and rat ovary. Frozen sections were incubated with polyclonal antibody to human recombinant TNF. Antigen-antibody binding was visualized using a Biotin-StreptAvidin peroxidase technique. Immunoreactive TNF (I-TNF) was localized in corpora lutea and the more antral layers of granulosa cells in antral follicles. Incubation of sections with anti-TNF in the presence of excess TNF resulted in lose of immunostaining. Cell blotting and ELISA further indicated I-TNF was present in granulosa cells. In order to determine whether TNF had an effect on follicular steroidogenesis, preovulatory follicles from cyclic proestrus rats were incubated in vitro for up to 24 hours with various doses of human recombinant TNF. Stepwise increases in progesterone (P) accumulation in the incubation media were observed with 30-300 pM TNF.

  17. Virilizing ovarian tumor of cell tumor type not otherwise specified: a case report.

    PubMed

    Faraj, G; Di Gregorio, S; Misiunas, A; Faure, E N; Villabrile, P; Stringa, I; Petroff, N; Bur, G

    1998-10-01

    Whereas ovarian tumors with overt endocrine manifestations account for less than 5% of all ovarian neoplasms, the incidence of virilizing type tumors in postmenopausal women is even lower since the average age of occurrence is 43 years. Steroid cell tumors not otherwise specified (NOS) are even more rare. We report the case of a 56-year-old woman (age of onset of menopause 43 years) who consulted our service due to a hyperandrogenic syndrome: deepening of the voice, temporal balding, hirsutism and cliteromegaly. Laboratory findings indicated hyperandrogenism in male range. The dexamethasone suppression test did not modify basal values, indicating that adrenal origin was unlikely. Transvaginal ultrasound disclosed multiple microcysts in the left ovary. Abdominal tomography was normal. Suspecting an ovarian tumor, bilateral oophorectomy was performed and a pediculate, 3 cm in diameter, was encountered in the left ovary. Histopathological studies determined it to be a virilizing ovarian tumor NOS. Postoperative recovery was fast; normal hormonal values were reached together with visible clinical improvement. This case is reported because this type of tumor is very infrequent in postmenopausal women, and because in this case it was the functional hormonal test that allowed tumor localization.

  18. A gastrointestinal stromal tumor (GIST) masquerading as an ovarian mass

    PubMed Central

    Carlomagno, Giorgio; Beneduce, Pasquale

    2004-01-01

    Background Malignant gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal tract. Myogenic gastrointestinal stromal tumor, a distinctive morphologic variant is characterized by an unusually prominent myxoid stromal background. Case presentation We report a case of myxoid variant of GIST in a 42 years old woman presenting as an epigastric mass associated to an ovarian cyst and elevated CA-125. Histologically, the lesions was composed of a proliferation of spindle cells in an abundant myxoid stroma, without evidence of atypia or anaplasia. Immunohistochemical stains showed strong positive staining with muscle actin, positive staining with CD34 and weak positive staining with CD117, while showed negative for S-100. Conclusion At surgery every effort should be made to identify the origin of the tumor. A complete surgical removal of the tumor should be obtained, as this is the only established treatment that offers long term survival. PMID:15142276

  19. Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor

    PubMed Central

    Rozenblum, Ester; Sotelo-Silveira, Jose R.; Kim, Gina Y.; Zhu, Jack Y.; Lau, Christopher C.; McNeil, Nicole; Korolevich, Susana; Liao, Hongling; Cherry, James M.; Munroe, David J.; Ried, Thomas; Meltzer, Paul S.; Kuehl, Walter M.

    2017-01-01

    A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY), and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs)/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found). A large number of focal copy number alterations (FCNAs) were detected, including homozygous deletions (HDs) targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements). Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis. PMID:28787462

  20. FOXL2 mutation is absent in uterine tumors resembling ovarian sex cord tumors.

    PubMed

    Chiang, Sarah; Staats, Paul N; Senz, Janine; Kommoss, Friedrich; De Nictolis, Michele; Huntsman, David G; Gilks, C Blake; Oliva, Esther

    2015-05-01

    Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine neoplasms characterized by pure or predominant epithelial-like patterns that share morphologic, immunohistochemical, and ultrastructural features with ovarian sex cord tumors. FOXL2 immunoexpression has recently been found in sex cord stromal tumors of the ovary, including granulosa cell tumors, Sertoli-Leydig cell tumors, thecomas, and fibromas, but mutations have been identified mostly in adult granulosa cell tumors. In this study, we investigated FOXL2 mutation status and protein expression in UTROSCTs. Mutational analysis using a TaqMan real-time polymerase chain reaction-based allelic discrimination assay was performed on formalin-fixed, paraffin-embedded tissue from 15 UTROSCTs. FOXL2 mutation was absent in all tumors. FOXL2 immunoexpression was tested in all 15 tumors. Intensity of staining was scored as weak, moderate, or strong. Percentage of tumor cells with nuclear staining was recorded as follows: 0 (negative); 1+ (1% to 25%); 2+ (26% to 50%); 3+ (51% to 75%); and 4+ (76% to 100%). Nuclear expression of FOXL2 was present in 6 of 15 (40%) UTROSCTs. One tumor demonstrated strong 4+ staining. Moderate expression was seen in 3 cases, including 2 and 1 showing 2+ and 1+ staining, respectively. Weak expression was observed in 2 tumors demonstrating 3+ and 1+ staining. Although UTROSCTs show overlapping morphologic, immunohistochemical, and ultrastructural features with sex cord stromal tumors of the ovary, they do not harbor FOXL2 mutation despite focal immunoreactivity in a subset of these tumors.

  1. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

    PubMed Central

    Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

    2015-01-01

    Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

  2. Differential tumor microenvironment in human ovarian cystic tumors.

    PubMed

    Tavares Murta, Beatriz Martins; Cunha, Fernando de Queiróz; Miranda, Rodrigo; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2004-01-01

    Cells and soluble mediators obtained from tumor effusions are useful in evaluating the tumor microenvironment. Our aim was to examine cytologically and to quantify the leukocyte infiltrate, nitric oxide, cytokines and tumor markers in the intracystic fluid from patients with a cystic adnexal mass, for a possible differentiation between benign and malignant findings. Sixty-six women who had their cystic fluids collected were prospectively divided into benign tumor (22, 33.3%), malignant tumor (10, 15.2%) or other gynecological alterations (34, 51.5%). Cytology, total and differential leukocyte counts were determined by light microscopy. Tumor markers, cytokines and nitric oxide were assayed in the supernatants using the Immulite system, ELISA and Griess reaction, respectively. The sensitivity and specificity of the cytological analysis was 66.7% and 97.7%, respectively. The levels of CA 19.9, CA 15.3, alpha-fetoprotein, carcinoembryonic antigen, progesterone and beta-HCG were significantly higher in the benign and/or malignant group than in the other gynecological alterations. Also, the local concentrations of CA 15.3 and beta-HCG were significantly higher in malignant than in benign tumors. In malignant tumors, increased leukocyte counts and higher concentrations of IL-6, IL-10 and nitric oxide were detected than in benign tumors or other gynecological alterations. In malignant tumors, the microenvironment could be differentiated from benign tumors or other gynecological alterations by cystic fluid analysis.

  3. Expression of MAGE-C1/CT7 and selected cancer/testis antigens in ovarian borderline tumours and primary and recurrent ovarian carcinomas.

    PubMed

    Zimmermann, Anne-Katrin; Imig, Jochen; Klar, Agnes; Renner, Christoph; Korol, Dimitri; Fink, Daniel; Stadlmann, Sylvia; Singer, Gad; Knuth, Alexander; Moch, Holger; Caduff, Rosmarie

    2013-05-01

    MAGE-C1/CT7, NY-ESO-1, GAGE and MAGE-A4 are members of the cancer/testis (CT) antigen family, which have been proposed as potential targets for cancer immunotherapy. To determine the prevalence and biologic relevance of the novel CT antigen MAGE-C1/CT7 and other antigens, 36 ovarian borderline tumours (BTs), 230 primary ovarian carcinomas (OCs) and 80 recurrent OCs were immunohistochemically analysed using the monoclonal antibodies CT7-33 (MAGE-C1/CT7), E978 (NY-ESO-1), clone 26 (GAGE) and 57B (MAGE-A4). Positivity of at least one CT antigen was present in 39.5 % (81/205) of primary OC and in 50 % (26/52) of all recurrences. Expression of the novel CT antigen MAGE-C1/CT7 was most commonly seen with positivity in 24.5 % of primary and 35.1 % of recurrent OC. MAGE-A4, GAGE and NY-ESO-1 expressions were seen in 22.7, 13.9 and 7.1 % of primary and 22.6, 17.5 and 8.9 % of recurrent OC, respectively. Analysis of histological subtypes (serous, endometrioid, clear cell, mucinous and transitional) exhibited variable expression with negativity in all mucinous OC. High-grade serous OC revealed CT antigen expression in 5.6 to 28 % with MAGE-C1/CT7 being the most frequent, but without correlation with stage or overall survival. MAGE-C1/CT7 expression and coexpression of CT antigens were significantly correlated with grade of endometrioid OC. None of the BT showed CT antigen expression. No significant correlation was seen with stage, overall survival or response to chemotherapy. In summary, CT antigens are expressed in a certain subset of OC with no expression in BT or OC of mucinous histology. These findings may have implications for the design of polyvalent vaccination strategies for ovarian carcinomas.

  4. Genetics and genomics of ovarian sex cord-stromal tumors.

    PubMed

    Fuller, P J; Leung, D; Chu, S

    2017-02-01

    Ovarian sex cord-stromal tumors (SCST) represent approximately 8% of malignant ovarian tumors. The most common are granulosa cell tumors (GCT) which account for approximately 90% of malignant SCST. Recent studies have unraveled the key genomic and genetic events contributing to their pathogenesis. SCST are found in the hereditary syndromes: Peutz-Jeghers syndrome, Ollier disease and Maffucci syndrome, and DICER1 syndrome. Genomic studies have largely been limited to GCT where a number of recurring chromosomal abnormalities (monsomy and trisomy) have been identified although their contribution to pathogenesis remains unclear. In addition to the recurrent DICER1 mutations reported in non-hereditary cases of Sertoli cell and Sertoli-Leydig cell tumors, recurrent somatic mutations in both the juvenile (j) and adult (a) forms of GCT have been reported. Approximately 30% of jGCT contain a somatic mutation, the gsp oncogene, while a further 60% have an activating mutation in the AKT gene. In the case of aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in almost all cases, which arguably defines the disease, although the molecular events that determine the stage, behavior and prognosis of aGCT remain to be determined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Uterine tumors resembling ovarian sex cord tumors: A case report and literature review

    PubMed Central

    CETINKAYA, NILUFER; BAS, SEVDA; CUYLAN, ZELIHA FIRAT; ERDEM, OZLEM; ERKAYA, SALIM; GUNGOR, TAYFUN

    2016-01-01

    Uterine tumors with ovarian sex cord-like elements are a rarely observed type of uterine body tumor with unknown etiology, and are divided into two groups: Endometrial stromal tumors with sex cord-like elements (ESTSCLEs) and uterine tumors resembling ovarian sex cord tumors (UTROSCTs). While ESTSCLEs are commonly associated with metastasis and recurrence, there is limited data in the relevant literature concerning the behavior of UTROSCTs. However, UTROSCTs are typically benign in nature. Although case numbers are limited, extra-uterine or lymph node metastasis has been reported. Surgical approaches may be altered according to the patient's age and desire for future fertility. Hysterectomies with bilateral salpingo-oopherectomy or hysteroscopic tumor resection are reported to be safe surgical treatment options. However, in the current report, a case of UTROSCT initially misdiagnosed as adenosarcoma following hysteroscopic tumor resection is presented. Staging surgery revealed the precise diagnosis of the tumor using appropriate immunohistochemical evaluations, and led to the discovery of a secondary tumor focus in the myometrium, adjacent to the location of the previously excised tumor. Thus, hysteroscopic resection is questionable as a definitive surgical treatment in patients exhibiting UTROSCT. If hysteroscopic resection is the selected treatment, close follow-up with diagnostic imaging is recommended. PMID:26893767

  6. [Prognostic analysis of benign, borderline and malignant phyllodes tumors of the breast].

    PubMed

    Wang, Hui; Wang, Xiang; Wang, Chengfeng

    2015-12-01

    To explore the prognosis of benign, borderline and malignant phyllodes tumors of the breast. Data from 246 women with phyllodes tumors of the breast treated in the Cancer Hospital, Chinese Academy of Medical Sciences between January 2002 and December 2012, were collected and analyzed retrospectively. The patients were followed-up for a median of 48 months (range 1-138 months). Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the factors affecting the disease-free survival. Among the 246 patients, 65 were dropped out from the follow-up. 56 patients had local recurrence, 5 patients had distant metastasis, while one case had both local recurrence and distant metastasis. The median disease-free survival time was 39 months. Kaplan-Meier survival analysis revealed that fibroadenoma history and type of primary surgery were associated to the disease-free survival of phyllodes tumors of the breast (P<0.001, P=0.043), while histological type and primary tumor size had no significant relationship with the disease-free survival (P=0.083, P=0.974). The multivariate Cox proportional hazard model showed that type of primary surgery, fibroadenoma history and histological types are all independent factors affecting the disease-free survival (P=0.009, P=0.001 and P<0.001). Phyllodes tumors of the breast have a relatively good prognosis on the whole. Type of primary surgery, fibroadenoma history and histological type are independent factors predicting the disease-free survival of patients with phyllodes tumors of the breast.

  7. Medial hypertrophy of the ovarian vein: a novel type of vascular pathology associated with a primary ovarian carcinoid tumor.

    PubMed

    Dessauvagie, Benjamin F; Lai, Patrick H; Oost, Ebo; Thomas, Anitha; Stewart, Colin J R

    2015-01-01

    Primary carcinoid tumors of the ovary are rare accounting for only 1% of neoplasms that are associated with the carcinoid syndrome. However, the carcinoid syndrome can occur in the absence of hepatic metastases due to the release of vasoactive peptides directly into the systemic circulation via the ovarian vein. We present a 69-yr-old woman presenting with carcinoid valvular disease and congestive cardiac failure who was found to have a primary left ovarian carcinoid tumor. At operation it was noted that the left ovarian vein had an unusually firm and thickened appearance, and histologic examination revealed marked fibromuscular medial hypertrophy with luminal compression. There was no associated vascular elastosis. This ovarian venous alteration appears to represent a novel addition to the spectrum of cardiovascular injuries associated with carcinoid tumors.

  8. Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-grade and High-grade Carcinomas

    PubMed Central

    Kuo, Kuan-Ting; Guan, Bin; Feng, Yuanjian; Mao, Tsui-Lien; Chen, Xu; Jinawath, Natini; Wang, Yue; Kurman, Robert J.; Shih, Ie-Ming; Wang, Tian-Li

    2009-01-01

    Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, was thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations while low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain largely unknown. As well, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well-studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG and HG tumors using high density 250K SNP arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions including homozygous deletions were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4% and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profiles in HG serous carcinomas, serving as a molecular foundation to study tumor suppressors in ovarian cancer. PMID:19383911

  9. Ovarian tumor-initiating cells display a flexible metabolism

    PubMed Central

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. PMID:25172556

  10. Ovarian tumor-initiating cells display a flexible metabolism

    SciTech Connect

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  11. Phyllodes tumor of borderline malignancy: seven year follow up with immunohistochemical study.

    PubMed

    Tomita, Tatsuo; Ren, Yafei; Davis, Marilyn; Tawfik, Ossama

    2005-09-01

    The patient was 80 years old when she initially presented with a left breast mass. Originally, a needle biopsy showed benign stromal and ductal cells. Five years later, the breast mass increased in size and a core needle biopsy showed a biphasic intraductal papillomatous tumor with cellular stroma. Eighteen months later, another biopsy was taken from the breast mass, revealing a well-developed phyllodes tumor (PT) of borderline malignancy. One month later, a simple mastectomy was performed for this 87-year-old woman. Histolopathologic and immunohistochemical studies, including estrogen and progesterone receptors, Ki-67 and p53, performed on tissues from the different biopsy specimens confirmed the progressive transition of the tumor in a 7 year period. An increase in mitotic activity was noted in the later samples. Similarly, percentages of p53- and Ki-67-positive cells were much higher in the stromal and ductal cells of the later samples compared to the original specimen. These findings support the notion that Ki-67 and p53 immunohistochemical staining may be used as simple and practical markers for the evaluation of the malignant potential of PT.

  12. Ovarian tumors with elevated CA-125 levels and severe juvenile hypothyroidism: a need for increased awareness.

    PubMed

    Krishnamurthy, Sriram; Seth, Anju; Puri, Archana; Anand, Rama; Aneja, Satinder

    2010-06-01

    A 15-yr-old girl presented with bilateral gross ovarian tumors, clinical features of long-standing unrecognized hypothyroidism and markedly elevated CA-125 levels. Ovarian resection was avoided, as the presentation was consistent with the Van Wyk and Grumbach syndrome; and the patient was treated with replacement of thyroid hormone. Regression of the ovarian tumors occurred 6 months after initiation of the treatment. The authors emphasise the need for increased awareness and screening for hypothyroidism in patients with ovarian tumors, in order to prevent inadvertent operative interventions.

  13. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    PubMed Central

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542

  14. Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) – a study of the TOC Consortium

    PubMed Central

    2014-01-01

    Background Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. Objective The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Methods Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. Results There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Conclusions Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants. PMID:24872845

  15. Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium.

    PubMed

    Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid

    2014-01-01

    Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

  16. Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer

    DTIC Science & Technology

    2010-03-01

    Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer PRINCIPAL INVESTIGATOR: Brad H. Nelson, Ph.D...CONTRACTING ORGANIZATION: British Columbia Cancer Agency, Victoria BC V8R 6V5...4. TITLE AND SUBTITLE Control of Disease Recurrence by Tumor-Infiltrating T Cells in 5a. CONTRACT NUMBER Ovarian Cancer 5b. GRANT NUMBER

  17. Isolation and Characterization of Tumor Cells from the Ascites of Ovarian Cancer Patients: Molecular Phenotype of Chemoresistant Ovarian Tumors

    PubMed Central

    Latifi, Ardian; Luwor, Rodney B.; Bilandzic, Maree; Nazaretian, Simon; Stenvers, Kaye; Pyman, Jan; Zhu, Hongjian; Thompson, Erik W.; Quinn, Michael A.; Findlay, Jock K.; Ahmed, Nuzhat

    2012-01-01

    Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR). AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125), epithelial cell adhesion molecule (EpCAM) and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12–14 weeks after intraperitoneal (i.p.) injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC) markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions. PMID:23056490

  18. Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

    DTIC Science & Technology

    2016-09-01

    particular we, have characterized stromal cell infiltration of ovarian tumors and have shown extensive infiltration of tumor associated blood vessels as well...migration on denatured collagen; it failed to reduce cell adhesion. Moreover a peptide antagonist of alpha 10 beta 1 may inhibit ovarian tumor growth in... cell infiltration was observed in tumors from alpha 10 beta 1 null mice. Moreover, our data suggest the presence of fibroblast that express integrin

  19. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    DOE PAGES

    Xu, Zhe; Wu, Chaochao; Xie, Fang; ...

    2014-10-28

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

  20. A mouse surgical model for metastatic ovarian granulosa cell tumor.

    PubMed

    Nadeau, Marie-Eve; Kaartinen, M Johanna; Laguë, Marie-Noëlle; Paquet, Marilène; Huneault, Louis M; Boerboom, Derek

    2009-12-01

    We recently described a genetically engineered mouse model that develops ovarian granulosa cell tumors (GCTs) that mimic many aspects of the advanced human disease, including distant dissemination. However, because the primary tumors killed their hosts before metastases were able to form, the use of these mice to study metastatic disease required the development of a simple, reliable, and humane surgical protocol for the excision of large GCTs from debilitated mice. Here we describe a protocol involving multimodal anesthesia, tumor removal through ventral midline celiotomy and perioperative fluid therapy, and analgesia that led to the postoperative survival of more than 90% of mice, despite the removal of tumors representing as much as 10% of the animal's body weight. Intraabdominal recurrence of the GCT did not occur in surviving animals, but most developed pulmonary or adrenal metastases (or both) by 12 wk after surgery. We propose that this mouse model of metastatic GCT will serve as a useful preclinical model for the development of novel treatment modalities and diagnostic techniques. Furthermore, our results delineate anesthetic and surgical principles for the removal of large abdominal tumors from mice that will be applicable to other models of human cancers.

  1. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  2. Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

    PubMed Central

    Kotsopoulos, Joanne; Terry, Kathryn L.; Poole, Elizabeth M.; Rosner, Bernard; Murphy, Megan A.; Hecht, Jonathan L.; Crum, Christopher P.; Missmer, Stacey; Cramer, Daniel W.; Tworoger, Shelley S.

    2013-01-01

    Differentiating ovarian tumors based on developmental pathway may further our understanding of the disease. Traditionally, ovarian cancers were thought to arise from the ovarian surface epithelium; however, recent evidence suggests some tumors originate in the fallopian tube. We classified cases in a population-based case-control study (NECC) and two cohort studies (NHS/NHSII) by tumor dominance, a proxy for tissue of origin. Dominant tumors (likely ovarian origin) are restricted to one ovary or are at least twice as large on one ovary compared to the other. Ovarian cancer risk factors were evaluated in relation to dominant and non-dominant tumors (likely tubal origin) using polytomous logistic regression (NECC) or competing risks Cox models (NHS/NHSII). Results were combined using random-effects meta-analyses. Among 1,771 invasive epithelial ovarian cancer cases, we observed 1,089 tumors with a dominant mass and 682 with no dominant mass. Dominant tumors were more likely to be mucinous, endometrioid, or clear cell, whereas non-dominant tumors were more likely to be serous. Tubal ligation, two or more births, endometriosis, and age were more strongly associated with dominant (RRs = 0.60, 0.83, 1.58, 1.37, respectively) than non-dominant tumors (RRs = 1.03, 0.93, 0.84, 1.14 p-difference = 0.0001, 0.01, 0.0003, 0.01, respectively). These data suggest that risk factors for tumors putatively arising from ovarian versus fallopian tube sites may differ; in particular, reproductive factors may be more important for ovarian-derived tumors. As this is the first study to evaluate ovarian cancer risk factors by tumor dominance, these results need to be validated by other studies. PMID:23364849

  3. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    PubMed

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

  4. Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

    PubMed Central

    Kwon, Mi Jeong; Shin, Young Kee

    2013-01-01

    Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

  5. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  6. Pulmonary papillary serous adenocarcinoma with intraperitoneal and ovarian tumors: identification of primary site. A case report.

    PubMed

    Chen, M-Y; Jung, S-M; Ng, K-K; Chang, T-C

    2006-01-01

    Papillary serous adenocarcinoma has been recognized as a highly malignant ovarian cancer and is also not uncommonly seen in primary lung cancer. Difficulty may exist in determining the origin of the primary tumor in women with synchronous pulmonary and ovarian tumors. We present a patient who was initially diagnosed and treated as stage IV papillary serous ovarian cancer with diffuse pulmonary metastases. Only transient symptomatic improvement was achieved after standard chemotherapy for ovarian cancer, and then she died of respiratory distress during treatment. Poor tumor response to chemotherapy prompted us to reevaluate the previous bronchoscopic biopsy, and immunohistochemical studies, which were cytokeratin (CK) 7 positive, CK20 negative, and thyroid transcription factor-1 (TTF-1)-positive, provided irrefutable evidences for the diagnosis of primary lung cancer. We suggest that in dealing with coexistence of ovarian and pulmonary tumors, immunohistochemical study by using CK7, CK20, and TTF-1 may be helpful in the differentiation of the primary origin.

  7. Tumor Stroma Engraftment of Gene-Modified Mesenchymal Stem Cells as Anti-Tumor Therapy against Ovarian Cancer

    PubMed Central

    Dembinski, Jennifer L.; Wilson, Shanna M.; Spaeth, Erika L.; Studeny, Matus; Zompetta, Claudia; Samudio, Ismael; Roby, Katherine; Andreeff, Michael; Marini, Frank C.

    2013-01-01

    Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment. Using both syngenic mouse tumors (ID8-R), and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed intraperitoneally-circulating MSC could target, preferentially engraft and differentiate into α-SMA+ myofibroblasts, suggesting their role as “reactive stroma” in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-beta (IFNβ). Then, mice with ovarian carcinomas received weekly IP injections of IFNβ expressing MSC, resulting in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFNβ delivered by murine MSC in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSC produced IFNβ induced caspase-dependent tumor cell apoptosis. Our results demonstrate that ovarian carcinoma engraft MSC to participate in myofibrovascular networks and that IFNβ produced by MSC intratumorally modulates tumor kinetics, resulting in prolonged survival. PMID:23260083

  8. Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors.

    PubMed

    Nomelini, Rosekeila Simões; de Abreu Ribeiro, Lívia Carolina; Tavares-Murta, Beatriz Martins; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2008-01-01

    Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 microM were more frequent than NO levels <80 microM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis.

  9. Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

    PubMed Central

    Nomelini, Rosekeila Simões; Ribeiro, Lívia Carolina de Abreu; Tavares-Murta, Beatriz Martins; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2008-01-01

    Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis. PMID:19132106

  10. A case of carcinoid tumor of the terminal ileum and simultaneous ovarian dermoid cyst.

    PubMed

    Hamada, Hosam

    2011-04-01

    Carcinoid tumors are slow-growing malignant neoplasms associated with an indolent clinical course. About 60% of such tumors are located within the gastrointestinal tract. Here, we describe the first case, to our knowledge, of a carcinoid tumor of the terminal ileum and a simultaneous ovarian dermoid cyst. A 57-year-old woman was presented with abdominal pain, vomiting, and clinical signs of mechanical bowel obstruction. Radiograph and computed tomography scan of the abdomen showed hydroaeric levels. Laparotomy revealed a mass in the terminal ileum and a right ovarian cystic mass. Right hemicolectomy and right oopherectomy were performed. The histopathological workup showed a carcinoid tumor of the terminal ileum and ovarian dermoid cyst. Small intestinal carcinoid tumor, an uncommon disease, has been reported earlier to coincide with various neoplasms. No association between small intestinal carcinoid tumor and ovarian dermoid cyst has been reported earlier in the English literature.

  11. Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

    DTIC Science & Technology

    2015-07-01

    elements to that of a biomechanical ECM switch, in which structural alterations in these molecules initiated by either proteolytic cleavage or other...absence of anti-HU177 antibody (100µg/ embryo ). Tumors were allowed to grow for 7 days and wet weights determined. For murine experiments, nude (NCRNU-F...in ovarian tumor growth. To examine this possibility, SKOV-3 ovarian tumor cells were seeded on the chorioallantoic membrane (CAM) of chick embryos

  12. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

    PubMed Central

    Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

    2016-01-01

    Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

  13. Potential role of increasing number of sections in frozen section diagnosis of ovarian tumors.

    PubMed

    Ayhan, Ali; Ozler, Ali; Dursun, Polat; Haberal, A Nihan

    2016-11-01

    To assess the accuracy of intraoperative frozen section of ovarian tumours at our institution and to identify the possible reasons for misdiagnosis. Between January 2002 and August 2013, a total of 684 patients were included in the study. Frozen section diagnosis was compared with the final paraffin section diagnosis as the gold standard. The sensitivity, specificity, and positive and negative predictive values of frozen-section diagnosis were calculated for benign, borderline and malignant tumours. Clinicopathological parameters influenced by misdiagnosis were evaluated performing multivariate logistic regression analysis. The overall accuracy was detected as 96.1%. Frozen-section diagnoses of 26 patients (3.8%) showed discordance. The specificity (99.7%) and PPV (99.4%) of frozen-section diagnosis was highest in the malignant category. In BOTs, diagnostic agreement was observed in 57 of 70 (81.4%) cases. The PPV (81.4%) was lowest for these patients. Tumour diameter of ≥10 cm (OR [95% CI]= 3.0 [1.1 to 8.2]; P=0.030) and mucinous histology (OR [95% CI]= 2.5 [1.0 to 6.2]; P=0.042) were significant predictors of misdiagnosis. With the increase in the number of sections, the accuracy rate of frozen section diagnosis was decreased. While not statistically significant (p=0.361). The number of sections is increased parallel to increase in tumor diameters. On the contrary, the diagnostic accuracy was no significantly increased with an increase in the number of sections. This discrepancy may be associated with falling tumor size per frozen section. A prospective study based on a certain tumour diameter per frozen section may better demonstrate the positive effect of the number of sections.

  14. Malignant tumors associated with ovarian mature teratoma: A single institution experience.

    PubMed

    Trabzonlu, Levent; Durmaz, Guray; Vural, Cigdem; Muezzinoglu, Bahar; Corakci, Aydin

    2017-05-01

    The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  16. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer.

    PubMed

    Chuong, Michael D; Frakes, Jessica M; Figura, Nicholas; Hoffe, Sarah E; Shridhar, Ravi; Mellon, Eric A; Hodul, Pamela J; Malafa, Mokenge P; Springett, Gregory M; Centeno, Barbara A

    2016-04-01

    While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

  17. Ovarian steroid cell tumor, not otherwise specified: A case report and literature review

    PubMed Central

    Qian, Lili; Shen, Zhen; Zhang, Xuefen; Wu, Dabao; Zhou, Ying

    2016-01-01

    Steroid cell tumors (SCT), not otherwise specified (NOS) are particularly rare ovarian sex cord-stromal tumors, which comprise <0.1% of all ovarian tumors. These tumors are uncommon in patients' prior to puberty without any typical syndromes involving hirsutism, virilization and hypertension. We here in present the case of a 5-year-old female patient who presented with sudden abdominal pain, repeated vomiting and a pelvic mass. Our patient underwent urgent exploratory laparotomy and right salpingo-oophorectomy and the histopathological examination revealed an ovarian SCT-NOS. The patient has been followed up for 5 years since the surgery, without evidence of disease recurrence. The purpose of this study was to discuss the available information on the presentation, diagnosis and recommended treatment of ovarian SCT-NOS; and describes the immunohistochemical characteristics of these tumors. PMID:28105366

  18. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    PubMed Central

    Nijman, HW; Lambeck, A; van der Burg, SH; van der Zee, AGJ; Daemen, T

    2005-01-01

    Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease. PMID:16164749

  19. Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.

    PubMed

    Munakata, Satoru; Yamamoto, Toshiya

    2015-01-01

    Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.

  20. Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

    PubMed

    Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

    2017-06-01

    Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  2. Correlation between tumor histology, steroid receptor status, and adenosine deaminase complexing protein immunoreactivity in ovarian cancer.

    PubMed

    Rao, B R; Slotman, B J; Geldof, A A; Dinjens, W N

    1990-01-01

    Adenosine deaminase complexing protein (ADCP) immunoreactivity was investigated in 40 ovarian tumors and correlated with clinicopathologic parameters, including tumor steroid receptor content. Ten (29%) of 34 common epithelial ovarian carcinomas showed ADCP reactivity. Reactivity for ADCP was seen more frequently in mucinous (100%; p less than 0.001), well-differentiated (73%; p less than 0.001) and Stage I (56%; p less than 0.05) ovarian carcinomas. Furthermore, tumors that contained high levels of androgen receptors and tumors that did not contain estrogen receptors were more frequently ADCP positive (p less than 0.05). However, after stratifying for histologic grade, no correlation between ADCP reactivity and receptor status was found. Determination of ADCP reactivity appears to be of limited value in ovarian cancer.

  3. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  4. Primary ovarian carcinoid tumor showing unusual histology and nuclear accumulation of β-catenin.

    PubMed

    Kim, Hyun-Soo; Yoon, Gun; Jang, Hye-In; Song, Sang Yong; Kim, Byoung-Gie

    2015-01-01

    Carcinoid tumor of the ovary is uncommon. We herein report a very rare case of primary ovarian carcinoid tumor with aggressive histology and an unusual immunophenotype. A 21-year-old woman presented with a palpable abdominal mass. Computed tomographic scan revealed a large, extensively necrotic solid mass in the left ovary. The patient underwent a left salpingo-oophorectomy. Grossly, the left adnexa showed a large, vaguely lobulated ovarian tumor measuring 22×15×13 cm. Histologically, the tumor had a readily identifiable neuroendocrine growth pattern, but some areas showed solid growth pattern associated with mild nuclear pleomorphism and multiple foci of punctate necrosis. Furthermore, mitotic figures were recognized in 8 per 10 high-power fields, and a few foci of large coagulative tumor necrosis were also noted. In addition, the tumor tissue exhibited uniform, strong nuclear β-catenin immunoreactivity, indicating the nuclear accumulation of β-catenin in the individual tumor cells. In summary, we described the first case of primary ovarian carcinoid tumor with loss of neuroendocrine growth pattern, increased mitotic activity and large areas of coagulative tumor necrosis. According to the WHO classification of pulmonary carcinoid tumor, this case may be classified as "atypical" carcinoid. However, currently, no primary ovarian atypical carcinoid exists in the classification system. Due to its rarity, there are no established diagnostic criteria and clinical data on patient outcomes for ovarian carcinoid tumors with aggressive histology. Additional reports are clearly necessary. We also showed for the first time the nuclear accumulation of β-catenin in carcinoid tumor cells, suggestive of a role for β-catenin in the tumorigenesis of ovarian atypical carcinoid tumor or its aggressive histology.

  5. Primary ovarian carcinoid tumor showing unusual histology and nuclear accumulation of β-catenin

    PubMed Central

    Kim, Hyun-Soo; Yoon, Gun; Jang, Hye-In; Song, Sang Yong; Kim, Byoung-Gie

    2015-01-01

    Carcinoid tumor of the ovary is uncommon. We herein report a very rare case of primary ovarian carcinoid tumor with aggressive histology and an unusual immunophenotype. A 21-year-old woman presented with a palpable abdominal mass. Computed tomographic scan revealed a large, extensively necrotic solid mass in the left ovary. The patient underwent a left salpingo-oophorectomy. Grossly, the left adnexa showed a large, vaguely lobulated ovarian tumor measuring 22×15×13 cm. Histologically, the tumor had a readily identifiable neuroendocrine growth pattern, but some areas showed solid growth pattern associated with mild nuclear pleomorphism and multiple foci of punctate necrosis. Furthermore, mitotic figures were recognized in 8 per 10 high-power fields, and a few foci of large coagulative tumor necrosis were also noted. In addition, the tumor tissue exhibited uniform, strong nuclear β-catenin immunoreactivity, indicating the nuclear accumulation of β-catenin in the individual tumor cells. In summary, we described the first case of primary ovarian carcinoid tumor with loss of neuroendocrine growth pattern, increased mitotic activity and large areas of coagulative tumor necrosis. According to the WHO classification of pulmonary carcinoid tumor, this case may be classified as “atypical” carcinoid. However, currently, no primary ovarian atypical carcinoid exists in the classification system. Due to its rarity, there are no established diagnostic criteria and clinical data on patient outcomes for ovarian carcinoid tumors with aggressive histology. Additional reports are clearly necessary. We also showed for the first time the nuclear accumulation of β-catenin in carcinoid tumor cells, suggestive of a role for β-catenin in the tumorigenesis of ovarian atypical carcinoid tumor or its aggressive histology. PMID:26191292

  6. Unusual liver locations of growing teratoma syndrome in ovarian malignant germ cell tumors.

    PubMed

    Lorusso, Domenica; Malaguti, Paola; Trivellizzi, Ilaria Nausica; Scambia, Giovanni

    2011-01-01

    ► Growing teratoma syndrome (GTS) with unusual liver locations are described after fertility preserving surgery and chemotherapy treatment for mixed malignant ovarian germ cell tumors (MGCT). ► It's a rare syndrome of mixed malignant ovarian germ cell tumors and in both cases enlarged and growing liver masses appeared during cisplatin-etoposide-bleomicin (BEP) chemotherapy. ► Radiological exams (CT scan and MRI) were suggestive for secondary metastasis and serum markers became negative during chemotherapy.

  7. [Giant ovarian tumor--case report and proposal for clinical management].

    PubMed

    Stukan, Maciej; Dudziak, Mirosław; Pawłowski, Maciej

    2011-02-01

    A case report of a woman with 90 kg ovarian tumor is presented. Paracentesis and intravenous alimentation was performed before operation. During the surgery the ovarian tumor was excised and abdominal cavity packing, followed by slow pressure decreasing, was done. Intravenous together with oral alimentation was continued after the operation. The patient was discharged on the 10th postoperative day without any complications, in a good overall condition.

  8. FGF18 as a potential biomarker in serous and mucinous ovarian tumors.

    PubMed

    El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu

    2016-03-01

    Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.

  9. Ovarian Cancer Development and Metastasis

    PubMed Central

    Lengyel, Ernst

    2010-01-01

    The biology of ovarian carcinoma differs from that of hematogenously metastasizing tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity and are only superficially invasive. However, since the rapidly proliferating tumors compress visceral organs and are only temporarily chemosensitive, ovarian carcinoma is a deadly disease, with a cure rate of only 30%. There are a number of genetic and epigenetic changes that lead to ovarian carcinoma cell transformation. Ovarian carcinoma could originate from any of three potential sites: the surfaces of the ovary, the fallopian tube, or the mesothelium-lined peritoneal cavity. Ovarian cacinoma tumorigenesis then either progresses along a stepwise mutation process from a slow growing borderline tumor to a well-differentiated carcinoma (type I) or involves a genetically unstable high-grade serous carcinoma that metastasizes rapidly (type II). During initial tumorigenesis, ovarian carcinoma cells undergo an epithelial-to-mesenchymal transition, which involves a change in cadherin and integrin expression and up-regulation of proteolytic pathways. Carried by the peritoneal fluid, cancer cell spheroids overcome anoikis and attach preferentially on the abdominal peritoneum or omentum, where the cancer cells revert to their epithelial phenotype. The initial steps of metastasis are regulated by a controlled interaction of adhesion receptors and proteases, and late metastasis is characterized by the oncogene-driven fast growth of tumor nodules on mesothelium covered surfaces, causing ascites, bowel obstruction, and tumor cachexia. PMID:20651229

  10. Ovarian cancer-induced immunosuppression: relationship to tumor necrosis factor-alpha (TNF-alpha) release from ovarian tissue.

    PubMed

    Hassan, M I; Kassim, S K; Saeda, L; Laban, M; Khalifa, A

    1999-01-01

    Cytokines have been reported to be potential biological markers of, disease status in cancer patients. Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine released from monocytes and macrophages. TNF-alpha is involved in essential biological functions such as immunoregulation, modulation of cell growth and differentiation. In this work, the role of TNF-alpha release in ovarian cancer patients was investigated. Fifty-five patients with ovarian cancer and 20 controls of matched age and parity were included in this study. TNF-alpha concentrations were measured in sera and cytosolic fractions of both groups. The results demonstrated a significant increase in TNF-alpha concentrations among patients compared to the control subjects (P < 0.001). Furthermore, a non-significant increase (P = 0.05, was observed between the different types (serous, Mucinous, and endometrioid) of epithelial ovarian cancers. Also TNF-alpha concentrations did not correlate with the disease stage. Moreover, immunohistochemical analysis of tissue specimens stained for TNF-alpha was positive in malignant lesions and negative for the normal ovarian tissue. These findings confirmed the TNF-alpha kinetics obtained by ELISA assays. Interestingly, TNF-alpha levels were also elevated in culture supernatants of PBMC stimulated by cytosolic fractions from malignant ovarian tissues. Blastogenic assays using cytosolic fractions from malignant ovarian specimens to stimulate healthy donor peripheral blood mononuclear cells (PBMC) showed a marked decrease in 3H-thymidine uptake compared to the cells stimulated by normal cytosols. To establish a cause-effect relationship between TNF-alpha release and inhibition of cell proliferation, the experiments showed that 3H-thymidine uptake by PBMC was markedly inhibited by recombinant human TNF-alpha (rh TNF-alpha) and that inhibition was significantly reversed when TNF-alpha monoclonal antibody was added to the cells. The data presented in this work indicate that

  11. Expression of AQP6 and AQP8 in epithelial ovarian tumor.

    PubMed

    Ma, Jiong; Zhou, Chunxia; Yang, Jianhua; Ding, Xiaoyan; Zhu, Yunshan; Chen, Xuejun

    2016-04-01

    Aquaporins (AQPs), the rapid transition pores for water molecules, play an important role in maintenance of intracellular water balance. Studies showed that AQPs were also involved in occurrence, development, invasion and metastasis of tumors. In this study, we aimed to explore the distribution and expression differences of aquaporin 6 (AQP6) and aquaporin 8 (AQP8) in epithelial ovarian tumors. The expression of AQP6 and AQP8 in 47 cases of epithelial ovarian tumors were measured by immunochemical technique and Western blotting. AQP6 was strongly expressed in benign ovarian tumors, but weak signal was shown in malignant tumors. The difference was not statistically significant (P > 0.05). Compared with serous adenoma and normal tissues, AQP6 expression in serous carcinoma was obviously decreased (P < 0.05). AQP8 expressions were both identified in benign and malignant tumors, but there was no significantly statistical difference (P > 0.05). For patients with large volume of malignant ascites (>1000 ml), AQP8 expression was increased (P < 0.05). AQP8 expression in malignant tumors was not related to different clinical stages, presence of lymphatic metastasis, and differentiation degrees (P > 0.05). These data showed that AQP6 and AQP8 had different expression degrees in epithelial ovarian tissues, which suggests that AQP6 and AQP8 may play certain roles in epithelial ovarian tumors.

  12. Ovarian interstitial cell tumor in a South American sea lion (Otaria flavescens).

    PubMed

    Biancani, Barbara; Lacave, Geraldine; Magi, Gian Enrico; Rossi, Giacomo

    2010-07-01

    A case of an ovarian tumor is reported in an 8-yr-old South American sea lion (Otaria flavescens) kept in a marine park in Malta (35.57 degrees N, 14.25 degrees E). The neoplasm was a solid mass of dense sheets and nests of round to polyhedral, irregularly shaped cells with abundant, finely vacuolated cytoplasm. The nuclei were uniformly small and round to oval. The supporting stroma contained thecal cells. The tumor cells were positive for positive inhibin and vimentin and focally positive for cytokeratin by immunohistochemistry. The neoplasm was diagnosed as an ovarian sex cord-stromal tumor, specifically an interstitial cell tumor.

  13. Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells.

    PubMed

    Vera, C; Tapia, V; Kohan, K; Gabler, F; Ferreira, A; Selman, A; Vega, M; Romero, C

    2012-07-01

    Epithelial ovarian cancer is highly angiogenic and high expression of Nerve Growth Factor (NGF), a proangiogenic protein. Calreticulin is a multifunctional protein with anti-angiogenic properties and its translocation to the tumor cell membrane promotes recognition and engulfment by dendritic cells. The aim of this work was to evaluate calreticulin expression in human normal ovaries, benign and borderline tumors, and epithelial ovarian cancer samples and to evaluate whether NGF regulates calreticulin expression in human ovarian surface epithelium and in epithelial ovarian cancer cell lines. Calreticulin mRNA and protein levels were analyzed using RT-PCR, Western blot and immunohistochemistry in 67 human ovarian samples obtained from our Institution. Calreticulin expression induced by NGF stimulation in cell lines was evaluated using RT-PCR, Western blot and immunocytochemistry. We found a significant increase of calreticulin mRNA levels in epithelial ovarian cancer samples as compared to normal ovaries, benign tumors, and borderline tumors. Calreticulin protein levels, evaluated by Western blot, were also increased in epithelial ovarian cancer with respect to benign and borderline tumors. When HOSE and A2780 cell lines were stimulated with Nerve Growth Factor, we found an increase in calreticulin protein levels compared to controls. This effect was reverted by GW441756, a TRKA specific inhibitor. These results suggest that NGF regulates calreticulin protein levels in epithelial ovarian cells through TRKA receptor activation. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  15. Tumor promoting properties of the ETS protein MEF in ovarian cancer.

    PubMed

    Yao, J J; Liu, Y; Lacorazza, H D; Soslow, R A; Scandura, J M; Nimer, S D; Hedvat, C V

    2007-06-07

    We have previously shown that MEF (myeloid ELF1-like factor, also known as ELF4) functions as a transcriptional activator of the interleukin (IL)-8, perforin, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-3 genes in hematopoietic cells. MEF is also expressed in non-hematopoietic tissues including certain ovarian cancer cells. To define the function of MEF in these cells, we examined primary human ovarian epithelial tumors and found that MEF is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium. Manipulating MEF levels in these cell lines altered their behavior; reducing MEF levels, using short hairpin RNA expressing vectors, significantly inhibited the proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage-independent growth of CAOV3 cells. Overexpression of MEF in SKOV3 cells (via retroviral transduction) significantly increased their growth rate, enhanced colony formation in soft agar and promoted tumor formation in nude mice. The oncogenic activity of MEF was further shown by the ability of MEF to transform NIH3T3 cells, and induce their tumor formation in nude mice. MEF is an important regulator of the tumorigenic properties of ovarian cancer cells and could be used a therapeutic target in ovarian cancer.

  16. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    PubMed

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  17. Morphological and immunohistochemical re-evaluation of tumors initially diagnosed as ovarian endometrioid carcinoma with emphasis on high-grade tumors

    PubMed Central

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P.; Veras, Emmanuela; Park, Kay J.; Soslow, Robert A.

    2016-01-01

    Aims Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Methods Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): i) squamous metaplasia; ii) endometriosis; iii) adenofibromatous background; and iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Results Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years and 75% of patients were younger than 60 years. 92% presented with disease confined to the pelvis and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high-grade (grade 3 out of 3). 80% of cases had at least 1 CEF and 59% had at least 2 CEFs. 11% overexpressed p16, 0% overexpressed p53 and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were re-classified as serous carcinoma (OSC). The median patient age was 54.5 years and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one-half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular

  18. A Survey of DICER1 Hotspot Mutations in Ovarian and Testicular Sex Cord-Stromal Tumors

    PubMed Central

    Conlon, Niamh; Schultheis, Anne M; Piscuoglio, Salvatore; Silva, Annacarolina; Guerra, Esther; Tornos, Carmen; Reuter, Victor E; Soslow, Robert A; Young, Robert H; Oliva, Esther; Weigelt, Britta

    2015-01-01

    Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested 2 gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; p>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur

  19. A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors.

    PubMed

    Conlon, Niamh; Schultheis, Anne M; Piscuoglio, Salvatore; Silva, Annacarolina; Guerra, Esther; Tornos, Carmen; Reuter, Victor E; Soslow, Robert A; Young, Robert H; Oliva, Esther; Weigelt, Britta

    2015-12-01

    Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to

  20. NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas

    PubMed Central

    Yu, Yinhua; Xu, Fengji; Peng, Hongqi; Fang, Xianjun; Zhao, Shulei; Li, Yang; Cuevas, Bruce; Kuo, Wen-Lin; Gray, Joe W.; Siciliano, Michael; Mills, Gordon B.; Bast, Robert C.

    1999-01-01

    Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic growth of breast and ovarian cancer cells. Growth suppression was associated with down-regulation of the cyclin D1 promoter activity and induction of p21WAF1/CIP1. In an effort to identify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of heterozygosity of the gene was detected in 41% of ovarian and breast cancers. In most of cancer samples with loss of heterozygosity, the nonimprinted functional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast cancers. PMID:9874798

  1. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.

  2. Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

    PubMed Central

    Wrzeszczynski, Kazimierz O.; Varadan, Vinay; Byrnes, James; Lum, Elena; Kamalakaran, Sitharthan; Levine, Douglas A.; Dimitrova, Nevenka; Zhang, Michael Q.; Lucito, Robert

    2011-01-01

    The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates. PMID

  3. Single incision laparoscopic-assisted ovariohysterectomy for an ovarian tumor in a dog.

    PubMed

    Lopez, Daniel; Singh, Ameet; Wright, Tanya F; Gartley, Cathy; Walker, Meagan

    2017-09-01

    This report describes a single-incision, laparoscopic-assisted ovariohysterectomy in a 6-year-old, intact female Keeshond dog for the staging and treatment of a left-sided ovarian tumor. Abdominal access was obtained using a modified-Hasson technique allowing for placement of a multi-channel, single incision laparoscopic surgery port. Following carbon dioxide insufflation, superficial laparoscopic exploration of the abdominal cavity was performed and then both ovarian pedicles were sealed and divided using a vessel-sealing device. Laparoscopic-assisted ovariohysterectomy was performed with the aid of a wound retractor for exteriorization of the mass. There were no perioperative complications and the patient was discharged 1 day after surgery. Histopathology of the mass revealed an ovarian teratoma. Telephone follow-up 608 days after surgery revealed a good clinical outcome. Single-incision, laparoscopic-assisted ovariohysterectomy is technically feasible for the treatment of selected ovarian tumors in the dog.

  4. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    PubMed Central

    2010-01-01

    Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL), which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in metastasizing within the peritoneal

  5. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells.

    PubMed

    Gubbels, Jennifer A A; Felder, Mildred; Horibata, Sachi; Belisle, Jennifer A; Kapur, Arvinder; Holden, Helen; Petrie, Sarah; Migneault, Martine; Rancourt, Claudine; Connor, Joseph P; Patankar, Manish S

    2010-01-20

    Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL), which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16(low) targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in metastasizing within the peritoneal cavity and also at overcoming

  6. ShRNA-mediated silencing of the RFC3 gene suppress ovarian tumor cells proliferation

    PubMed Central

    Shen, Huimin; Xu, Juan; Zhao, Shanshan; Shi, Haijuan; Yao, Shuzhong; Jiang, Nan

    2015-01-01

    Ovarian carcinoma is one of the most common and lethal malignancies in the world. Replication factor C (RFC) plays an important role in DNA replication, DNA damage repair, and checkpoint control during cell cycle progression in all eukaryotes. Our previous study found that one unit of RFC complex, RFC3, is over-expressed in ovarian tumor tissues. However, its role in the development of ovarian carcinoma remains unclear. Western blot and real-time RT-PCR analysis were used to measure the expression of RFC3 in ovarian cancer cells. Lentivirus-mediated RFC3-specific shRNA was used to knock down RFC3 expression in ovarian cancer cells. Furthermore, the effect of RFC3 on tumor cellular proliferation and growth were examined, respectively. The expression level of RFC3 was remarkably up-regulated in ovarian cancer OVCAR-3 cells. With MTS and cell growth assays, the viability and proliferation of RFC3 knocking-down OVCAR-3 cell line were shown to be effectively restrained. Down-regulation of RFC3 expression arrested the cell cycle of OVCAR-3 cell in the S-phase and induced apoptosis. This study suggests that RFC3 may play an important role in the the process of ovarian carcinoma, and that it may be a potential biological treatment target in the future. PMID:26464638

  7. Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations

    DTIC Science & Technology

    2006-01-01

    gene knockout developed ovarian/ tubal tumors morphologically very similar to human ovarian serous cystadenomas in strong support of our hypothesis. We...proliferation activity in the uterus of 5 wild type and 5 mutant mice at the diestrus ad estrus phases of the estrus cycle. Histological cross- sections were...zygous knockout restricted to granulosa cells. One ovary was removed from each of 30 Brca1 flox/flox; Fshr-Cre mice at 2 months of age. Histological

  8. Identification of novel candidate plasma metabolite biomarkers for distinguishing serous ovarian carcinoma and benign serous ovarian tumors

    PubMed Central

    Buas, Matthew F.; Gu, Haiwei; Djukovic, Danijel; Zhu, Jiangjiang; Drescher, Charles W.; Urban, Nicole; Raftery, Daniel; Li, Christopher I.

    2017-01-01

    OBJECTIVE Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign ovarian tumor. METHODS Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. RESULTS Global lipidomics analysis identified 34 metabolites (of 372 assessed) differing significantly (P<0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q<0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P<0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD=0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC=0.91, SD=0.05) relative to CA125 alone (AUC=0.87, SD=0.07), particularly at high fixed levels of sensitivity, without reaching significance. CONCLUSIONS Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions. PMID:26521694

  9. Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth.

    PubMed

    Hu, Jianguo; Meng, Ying; Yu, Tinghe; Hu, Lina; Mao, Ming

    2015-05-20

    Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MARCH7 activated NFkB and Wnt/β-catenin pathways. Finally, MARCH7 was regulated by miR-101. Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

  10. Clinical experience of uterine tumors resembling ovarian sex cord tumors: a clinicopathological analysis of 6 cases

    PubMed Central

    Liu, Cai-Yan; Shen, Yan; Zhao, Jian-Guo; Qu, Peng-Peng

    2015-01-01

    Objective: To compare the clinicopathological features, diagnosis, treatment, and prognosis of two types of uterine sex cord-like tumors. Methods: The clinicopathological features of four uterine tumors resembling ovarian sex cord tumors (UTROSCTs) and two endometrial stromal tumors with sex cord-like elements (ESTSCLEs) were analyzed retrospectively. Results: All patients were premenopausal women. The most common clinical presentation was vaginal bleeding (four cases). Total hysterectomy with or without bilateral adnexectomy was the most common treatment pattern (five cases). A patient with UTROSCTs, presenting with recurrence 10 months after transvaginal submucous myomectomy, underwent a total hysterectomy (case 2). All tumors were polypoid or intramural masses, usually located in the uterine fundus or submucosa. The majority of UTROSCTs were positive for cytokeratin (4/4 cases), one was positive for Wilms tumor protein, and of two cases with smooth muscle actin immunoreactivity, two were positive for desmin. UTROSCTs were positive for two or more sex cord markers, whereas sex cord markers were less frequently detected in ESTSCLEs. CD10 was variably positive in two UTROSCT patients and strongly positive in all ESTSCLE patients. Three UTROSCTs and one ESTSCLE were positive for both estrogen and progesterone receptors. All patients with UTROSCTs were alive without evidence of recurrence. One patient with ESTSCLEs underwent postoperative chemotherapy after total vaginal hysterectomy but developed recurrence at the vaginal stump (case 5). The other patient with ESTSCLEs was lost to follow-up. Conclusion: These UTROSCTs are polymorphic neoplasms with true sex cord differentiation and uncertain malignant potential, which possess a distinct biology from ESTSCLEs. PMID:26097607

  11. Ovarian stromal tumor with minor sex cord elements with coexistent endometrial carcinoma.

    PubMed

    Kumar, Sunesh; Mathur, Sandeep; Subbaiah, Murali; Singh, Lavleen

    2013-01-01

    Ovarian stromal tumor with minor sex cord elements is a rare tumor. It is composed of predominantly fibrothecomatous tumor with scattered minor sex cord elements in less than 10% of the tumor area. These tumors may be hormonally active and predispose to carcinoma endometrium. A case of ovarian fibroma-thecoma with minor sex cord elements in which coexistent endometrial carcinoma was also discovered is being reported. Though thecoma may be a predisposing factor for endometrial cancer, meticulous histopathological examination of the ovary may reveal additional sources of estrogen like granulosa cell aggregates as in our patient. Such patients would require long-term follow-up to detect any recurrence of granulosa cell tumor.

  12. Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

    DTIC Science & Technology

    2013-10-01

    were examined. 3. Archived ultrasound images were examined off-line, ovarian tumor associated changes in gray scale intensity and Doppler indices...tumor was selected and the average image intensity (in pixel values) was determined using 7 Figure 1: Enhancement of ultrasound signal intensity ...16 targeted imaging agents increased ultrasound signal intensity remarkably in post-targeted imaging. The tumor showed septa of tissue mass during

  13. Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for HMGA2 expression.

    PubMed

    Agostini, Antonio; Brunetti, Marta; Davidson, Ben; Tropé, Claes G; Heim, Sverre; Panagopoulos, Ioannis; Micci, Francesca

    2017-03-28

    The High-mobility group AT-hook 2 protein (HMGA2) is involved in different processes during tumorigenesis. High expression levels of HMGA2 are found in various types of cancer, with recent studies highlighting the important role of miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas) analyzed for HMGA2 expression as well as the expression of two miRNAs targeting this gene, let-7a and miR-30c. We also evaluated the expression of the fragile histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to be an enhancer of miR-30c expression and a repressor of let-7a, respectively. HMGA2 was found expressed at high levels in most samples analyzed, with clear cell carcinomas as the only exception. let-7a and miR-30c were highly deregulated in all tumor types. LIN28A and FHIT were found overexpressed in all examined tumor types. The chromosomal imbalances that might lead to loss of the genes expressing let-7a and miR-30c could be evaluated on the basis of previously generated karyotypic and high resolution comparative genomic hybridization (CGH) data on 103 tumors. 76% of the samples with an imbalanced genome had at least one chromosomal aberration leading to a deletion of a miRNA cluster for let-7a and miR-30c. FISH using locus specific probes for these clusters validate the aberrations at the gene level. Our study shows that genomic imbalances are involved in miR-30c and let-7a deregulation. One can reasonably assume that dysregulation of these miRNAs is a cause leading to HMGA2 upregulation in ovarian tumors.

  14. Five-Year Disease-Free Follow-Up of a Borderline Breast Phyllodes Tumor in a 15-year-old Patient

    PubMed Central

    Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.

    2015-01-01

    Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.

  15. Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

    PubMed Central

    Ma, Wei; Ma, Jing; Xu, Jie; Qiao, Chong; Branscum, Adam; Cardenas, Andres; Baron, Andre T.; Schwartz, Peter; Maihle, Nita J.; Huang, Yingqun

    2013-01-01

    Emerging evidence suggests that the tumor microenvironment plays a critical role in regulating cancer stem cells (CSCs) and tumor progression through both autocrine and paracrine signaling. Elevated production of bone morphogenetic proteins (BMPs) from human ovarian cancer cells and stroma has been shown to increase CSC proliferation and tumor growth. Here, we report that Lin28, a stem cell factor, binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transcriptional level. As co-expression of Lin28 and Oct4 (another stem cell factor) has been implicated in ovarian cancer CSCs, we also determined that high levels of Lin28 are associated with an unfavorable prognosis when co-expressed with high levels of Oct4. Together, these findings uncover a new level of regulation of BMP4 expression and imply a novel Lin28/Oct4/BMP4-mediated mechanism of regulating ovarian tumor cell growth, thus holding potential for the development of new strategies for the diagnosis and treatment of ovarian cancer. PMID:23255092

  16. Uterine tumor resembling ovarian sex cord tumor. Case report and review of literature.

    PubMed

    Stefanovic, A; Jeremic, K; Kadija, S; Mitrovic, M; Filimonovic, D; Jankovic-Raznatovic, S; Tavcar, J

    2013-01-01

    A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord markers, as well as hormone receptors. The authors present a case of a 59-year-old multiparous woman admitted to the Institute of Gynecology and Obstetrics Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of 100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas sized 54 x 69 mm located in fundus with secondary changes. She underwent abdominal hysterectomy with adnexectomy. Microscopic examination revealed submucosal uterine tumor with variabile histological organization that had anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10 HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and ER(+). The poly phenotypic immunophenotype can be useful in differential diagnosis from other neoplasms but also suggests an origin of UTROSCT from uncommitted stem cell enabling for multidirectional differentiation.

  17. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.

    PubMed

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  18. Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

    PubMed

    Croce, Sabrina; de Kock, Leanne; Boshari, Talia; Hostein, Isabelle; Velasco, Valerie; Foulkes, William D; McCluggage, W Glenn

    2016-07-01

    Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

  19. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  20. Expression of Leukocyte Inhibitory Immunoglobulin-like Transcript 3 Receptors by Ovarian Tumors in Laying Hen Model of Spontaneous Ovarian Cancer.

    PubMed

    Khan, Mohammad Faisal; Bahr, Janice M; Yellapa, Aparna; Bitterman, Pincas; Abramowicz, Jacques S; Edassery, Seby L; Basu, Sanjib; Rotmensch, Jacob; Barua, Animesh

    2012-04-01

    Attempts to enhance a patient's immune response and ameliorate the poor prognosis of ovarian cancer (OVCA) have largely been unsuccessful owing to the suppressive tumor microenvironment. Leukocyte immunoglobulin-like transcript 3 (ILT3) inhibitory receptors have been implicated in immunosuppression in several malignancies. The expression and role of ILT3 in the progression of ovarian tumors are unknown. This study examined the expression and association of ILT3 in ovarian tumors in laying hens, a spontaneous preclinical model of human OVCA. White Leghorn laying hens were selected by transvaginal ultrasound scanning. Serum and normal ovaries or ovarian tumors were collected. The presence of tumors and the expression of ILT3 were examined by routine histology, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction. In addition to stromal immune cell-like cells, the epithelium of the ovarian tumors also expressed ILT3 with significantly high intensity than normal ovaries. Among different subtypes of ovarian carcinomas, serous OVCA showed the highest ILT3 staining intensity, whereas endometrioid OVCA had the lowest intensity. Similar to humans, an immunoreactive protein band of approximately 55 kDa for ILT3 was detected in the ovarian tumors in hens. The patterns of ILT3 protein and messenger RNA expression by ovarian tumors in different subtypes and stages were similar to those of immunohistochemical staining. The results of this study suggest that laying hens may be useful to generate information on ILT3-associated immunosuppression in OVCA. This animal model also offers the opportunity to develop and test anti-ILT3 immunotherapy to enhance antitumor immunity against OVCA in humans.

  1. PKC iota promotes ovarian tumor progression through deregulation of cyclin E

    PubMed Central

    Nanos-Webb, Angela; Bui, Tuyen; Karakas, Cansu; Zhang, Dong; Carey, Jason P.W.; Mills, Gordon B.; Hunt, Kelly K.; Keyomarsi, Khandan

    2016-01-01

    The high frequency of relapse of epithelial ovarian tumors treated with standard chemotherapy has highlighted the necessity to identify targeted therapies that can improve patient outcomes. The dynamic relationship between Cyclin E and PKCiota frequent overexpression in high-grade ovarian tumors poses a novel pathway for therapeutic investigation. We hypothesized that a PI3K dependent signaling pathway activating PKCiota perpetuates cyclin E deregulation during ovarian tumorigenesis. We observed a positive correlation between PKCiota and cyclin E in a panel of 19 ovarian cancer cell lines. Modulation of cyclin E had no effect on PKCiota knockdown/overexpression however PKCiota differentially regulated cyclin E expression. In the serous ovarian cancer cells (IGROV, OVCAR-3), shPKCiota decreased proliferation, caused a G1 arrest, and significantly prolonged overall survival in xenograft mouse models. In vitro shPKCiota decreased the ability of IGROV cells to grow under anchorage independent conditions and form aberrant acini, which was dependent upon Ad-cyclin E or Ad-LMW-E expression. RPPA analysis of PKCiota wild-type, catalytic active, dominant negative protein isoforms strengthened the association between phospho-PKCiota levels and PI3K pathway activation. Inhibitors of PI3K coordinately decreased phospho-PKCiota and Cyclin E protein levels. In conclusion, we have identified a PI3K/PKCiota/Cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. PMID:26279297

  2. Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T Cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages

    DTIC Science & Technology

    2011-07-01

    will be delivered to separate T-cell populations using the SFG retroviral vector and retronectin - coated tissue culture dishes: (i) HOX – targets MUC1 and...cancer. Patient derived T-cells were activated with CSD3+CD28- coated beads and transduced with retroviral expression vectors. A representative example for...cells from ascites and tumor tissue stained from a patient with ovarian cancer. Tumor cells were separated using magnetic beads coated with antibodies

  3. [Ovarian carcinoid tumor responsible of permanent facial erythrosis and flushings during sexual intercourse].

    PubMed

    Talvande, B; Dorange, A; Lecouflet, M; Le Nezet, M; Kianifard, B; Maillard, H; Duquenne, M

    2016-11-01

    Ovarian neuroendocrine tumors are extremely rare. In the ovary, the term of neuroendocrine tumor is usually related to carcinoid tumors although it may be sometimes applied to neuroendocrine carcinomas of non-small cells or small cells cancers usually occurring in the lungs. These carcinoid tumors may develop de novo or from other tumors including teratomas. We report a patient who presented with an ovarian carcinoid tumor developed, near or from a dermoid cyst, which was original by its mode of discovery in the dermatology department. Indeed, the patient consulted because of permanent facial erythrosis, with flushes but also facial telangiectasias. During medical examination, classic symptoms of carcinoid syndrome including heart disease were obvious. The occurrence of flushes during coitus should evoke pelvic tumor location. A carcinoid syndrome is naturally evoked in the presence of flushes but it must also be part of the differential diagnosis in a patient with facial erythrosis or telangiectasias, especially if they are associated with diarrhea or right heart failure. The prognosis of carcinoid heart disease is considerably better in case of ovarian location than when it is a primitive carcinoid tumor of lung or from gastrointestinal tract. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones.

    PubMed

    Nunez, Nomeli P; Perkins, Susan N; Smith, Nicole C P; Berrigan, David; Berendes, David M; Varticovski, Lyuba; Barrett, J Carl; Hursting, Stephen D

    2008-01-01

    Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.

  5. Modulating the tumor immune microenvironment as an ovarian cancer treatment strategy

    PubMed Central

    Scarlett, Uciane K.; Conejo-Garcia, Jose R.

    2013-01-01

    After more than 30 years of iterations of surgical debulking plus chemotherapy, the need for complementary ovarian cancer treatments has become clear. In the ovarian cancer microenvironment, myeloid immunosuppressive leukocytes, lymphocytes, fibroblasts and endothelial cells, as well as their secreted products, surface molecules and paracrine survival factors, all provide opportunities for novel interventions. The potential of targeting microenvironmental elements in ovarian cancer patients is underscored by recently successful anti-angiogenic therapies. The compartmentalized nature of ovarian cancer, its immunogenicity and its accessibility make it an ideal disease for targeting non-tumor host cells. This review discusses the ‘state-of-the-art’ of the field, with an emphasis on the potential of modulating the activity of abundant microenvironmental immune cells, which govern both angiogenesis and immunosuppression. PMID:24039628

  6. Silencing of p130Cas in Ovarian Carcinoma: A Novel Mechanism for Tumor Cell Death

    PubMed Central

    Nick, Alpa M.; Stone, Rebecca L.; Armaiz-Pena, Guillermo; Ozpolat, Bulent; Tekedereli, Ibrahim; Graybill, Whitney S.; Landen, Charles N.; Villares, Gabriel; Vivas-Mejia, Pablo; Bottsford-Miller, Justin; Kim, Hye Sun; Lee, Ju-Seog; Kim, Soo Mi; Baggerly, Keith A.; Ram, Prahlad T.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel

    2011-01-01

    Background We investigated the clinical and biological significance of p130cas, an important cell signaling molecule, in ovarian carcinoma. Methods Expression of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated with tumor characteristics and patient survival. The effects of p130cas gene silencing with small interfering RNAs incorporated into neutral nanoliposomes (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth and on tumor cell proliferation (proliferating cell nuclear antigen) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the specific mechanisms by which p130cas gene silencing abrogates tumor growth, we measured cell viability (MTT assay), apoptosis (fluorescence-activated cell sorting), autophagy (immunoblotting, fluorescence, and transmission electron microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests were two-sided. Results Of 91 ovarian cancer specimens, 70 (76%) had high p130cas expression; and 21 (24%) had low p130cas expression. High p130cas expression was associated with advanced tumor stage (P < .001) and higher residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and inversely associated with overall survival and progression-free survival (median overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years, difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001; median progression-free survival: high p130cas expression vs low expression, 1.04 vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60 years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1 ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel chemotherapy resulted in the greatest

  7. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    PubMed

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

  8. Effect of reproductive hormones on ovarian epithelial tumors: II. Effect on angiogenic activity.

    PubMed

    Chen, Chen; Petitclerc, Eric; Zhou, Hong; Brooks, Peter C; Sun, Tong; Yu, Mimi C; Zheng, Wenxin; Dubeau, Louis

    2002-01-01

    Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.

  9. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

    PubMed Central

    Hua, Yuanyuan; Choi, Pui-Wah; Trachtenberg, Alexander J.; Ng, Allen C.; Kuo, Winston P.; Ng, Shu-Kay; Dinulescu, Daniela M.; Matzuk, Martin M.; Berkowitz, Ross S.; Ng, Shu-Wing

    2016-01-01

    Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis. PMID:27602775

  10. The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells

    PubMed Central

    Kulbe, Hagen; Thompson, Richard; Wilson, Julia L.; Robinson, Stephen; Hagemann, Thorsten; Fatah, Rewas; Gould, David; Ayhan, Ayse; Balkwill, Frances

    2009-01-01

    Constitutive expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) is characteristic of malignant ovarian surface epithelium. We investigated the hypothesis that this autocrine action of TNF-α generates and sustains a network of other mediators that promote peritoneal cancer growth and spread. When compared with two ovarian cancer cell lines that did not make TNF-α, constitutive production of TNF-α was associated with greater release of the chemokines CCL2 and CXCL12, the cytokines interleukin-6 (IL-6) and macrophage migration-inhibitory factor (MIF), and the angiogenic factor vascular endothelial growth factor (VEGF). TNF-α production was associated also with increased peritoneal dissemination when the ovarian cancer cells were xenografted. We next used RNA interference to generate stable knockdown of TNF-α in ovarian cancer cells. Production of CCL2, CXCL12, VEGF, IL-6, and MIF was decreased significantly in these cells compared with wild-type or mock-transfected cells, but in vitro growth rates were unaltered. Tumor growth and dissemination in vivo were significantly reduced when stable knockdown of TNF-α was achieved. Tumors derived from TNF-α knockdown cells were noninvasive and well circumscribed and showed high levels of apoptosis, even in the smallest deposits. This was reflected in reduced vascularization of TNF-α knockdown tumors. Furthermore, culture supernatants from such cells failed to stimulate endothelial cell growth in vitro. We conclude that autocrine production of TNF-α by ovarian cancer cells stimulates a constitutive network of other cytokines, angiogenic factors, and chemokines that may act in an autocrine/paracrine manner to promote colonization of the peritoneum and neovascularization of developing tumor deposits. PMID:17234767

  11. Solid pseudopapillary tumor: an invasive case report of primary ovarian origin and review of the literature

    PubMed Central

    He, Shuqian; Yang, Xiaoqing; Zhou, Ping; Cheng, Yuxia; Sun, Qing

    2015-01-01

    Solid pseudopapillary neoplasm occurring as a primary tumor outside the pancreas is a rare event. We report a case of an ovarian primary occurring with an ill-defined cystic mass in a 39-year-old woman. The morphologic and immunohistochemical features of the ovarian neoplasm described in this report are compatible with those of solid pseudopapillary neoplasm of the pancreas. Histologically, the tumor cells of the case we report infiltrate into the ovarian parenchyma. Because of the diagnosis is not clear before surgery, the patient had a reoccurrence two months after the operation in which laparoscopic simple ovarian cystectomy and part ovarian tissue removal, followed by the right salpingo-oophorectomy. The case herein confirms that solid pseudopapillary neoplasm of the ovary belongs to the class of low-grade malignant tumor with certain invasiveness. The diagnosis should be taken into serious consideration in order to avoid missed diagnosis and delay treatment. Through this case we have a better understanding of the biological behavior of solid pseudopapillary neoplasm of the ovary. PMID:26339451

  12. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  13. Biochemical composition of malignant ascites determines high aggressiveness of undifferentiated ovarian tumors.

    PubMed

    Mikuła-Pietrasik, Justyna; Uruski, Paweł; Szubert, Sebastian; Moszyński, Rafał; Szpurek, Dariusz; Sajdak, Stefan; Tykarski, Andrzej; Książek, Krzysztof

    2016-08-01

    Although undifferentiated tumors are the most lethal among all ovarian cancer histotypes, the exact reasons for this situation are unclear. This report was aimed at investigating whether the high aggressiveness of undifferentiated ovarian cancer may be associated with a biochemical composition of malignant ascites accumulating in the peritoneal cavity. We analyzed ascites from patients with undifferentiated, high-grade serous, endometrioid and clear-cell ovarian cancers, and from non-cancerous patients with respect to a group of soluble agents involved in cancer cell progression. Moreover, the effect of these fluids on proliferation and migration of ovarian cancer cells (A2780, OVCAR-3 and SKOV-3) was evaluated. The study showed that the level of all tested proteins in malignant ascites was higher than in the benign fluids. Concentration of 9/11 agents (CCL2, CXCL1, CXCL5, CXCL8, CXCL12, HGF, PAI-1, TGF-β1 and VEGF) was the greatest in the fluids from undifferentiated cancer, while the level of remaining 2 (IL-6 and uPA) was the highest in ascites from serous carcinoma. Proliferation of cancer cells was the most effective when they were subjected to ascites from patients with undifferentiated and serous cancer, whereas the migration was the highest in the case of undifferentiated tumors. Our findings indicate that the aggressiveness of undifferentiated ovarian tumors may be associated with the composition of malignant ascites, in particular the concentration of specific proinflammatory, cancer-promoting agents.

  14. Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer

    PubMed Central

    Zhang, Weijing; Li, Han; Ou, Yulan; Song, Libing

    2017-01-01

    Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients. PMID:28758939

  15. Targeted endostatin-cytosine deaminase fusion gene therapy plus 5-fluorocytosine suppresses ovarian tumor growth.

    PubMed

    Sher, Y-P; Chang, C-M; Juo, C-G; Chen, C-T; Hsu, J L; Lin, C-Y; Han, Z; Shiah, S-G; Hung, M-C

    2013-02-28

    There are currently no effective therapies for cancer patients with advanced ovarian cancer, therefore developing an efficient and safe strategy is urgent. To ensure cancer-specific targeting, efficient delivery, and efficacy, we developed an ovarian cancer-specific construct (Survivin-VISA-hEndoyCD) composed of the cancer specific promoter survivin in a transgene amplification vector (VISA; VP16-GAL4-WPRE integrated systemic amplifier) to express a secreted human endostatin-yeast cytosine deaminase fusion protein (hEndoyCD) for advanced ovarian cancer treatment. hEndoyCD contains an endostatin domain that has tumor-targeting ability for anti-angiogenesis and a cytosine deaminase domain that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic drug, 5-fluorouracil. Survivin-VISA-hEndoyCD was found to be highly specific, selectively express secreted hEndoyCD from ovarian cancer cells, and induce cancer-cell killing in vitro and in vivo in the presence of 5-FC without affecting normal cells. In addition, Survivin-VISA-hEndoyCD plus 5-FC showed strong synergistic effects in combination with cisplatin in ovarian cancer cell lines. Intraperitoneal (i.p.) treatment with Survivin-VISA-hEndoyCD coupled with liposome attenuated tumor growth and prolonged survival in mice bearing advanced ovarian tumors. Importantly, there was virtually no severe toxicity when hEndoyCD is expressed by Survivin-VISA plus 5-FC compared with CMV plus 5-FC. Thus, the current study demonstrates an effective cancer-targeted gene therapy that is worthy of development in clinical trials for treating advanced ovarian cancer.

  16. The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

    PubMed Central

    Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

    2016-01-01

    Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576

  17. [Metastatic tumors in the ovary, difficulties of histologic diagnosis].

    PubMed

    Tamás, Judit; Vereczkey, Ildikó; Tóth, Erika

    2015-09-01

    The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections.

  18. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2011-09-01

    We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.

  19. [Secondary amenorrhea and LH hypersecretion. An unusual report of a granulosa cell ovarian tumor].

    PubMed

    Arteaga, E; Campusano, C; Fernández, C

    1993-04-01

    Granulosa cell ovarian tumors are infrequent. Since they originate from the gonadal stroma, they retain a high secretory potential and some of their clinical manifestations may be secondary to the production of sexual steroids. A 36 year old woman with an ovarian tumor presenting as a secondary amenorrhea is reported. This patient had a positive progesterone test and her hormonal profile showed a maintained LH hypersecretion (> 75 mUl/ml) which, joined to the presence of a hypophyseal microadenoma lead to suspect the presence of a gonadotrophin secreting tumor. The absence of LH response to TRH and its adequate suppression using oral contraceptives discarded this diagnosis. The histopathology of the excised ovarian tumor demonstrated that it is was a granulosa cell tumor. The physiopathological explanation of the case is based on the maintained levels of estrogens produced by the tumor that, through a positive feed-back mechanism similar to that of the polycystic ovary syndrome, produced a tonic LH elevation and GnRH hyper response. After the tumor excision, ovulatory cycles resumed and the patient became pregnant, facts that confirm the postulated hypothesis.

  20. Bioprosthetic tricuspid valve replacement in carcinoid heart disease from primary ovarian carcinoid tumor.

    PubMed

    Tsugu, Toshimitsu; Iwanaga, Shiro; Murata, Mitsushige; Fukuda, Keiichi

    2015-07-01

    Carcinoid heart disease (CHD) commonly occurs in association with primary gastrointestinal tract carcinoid tumors with hepatic metastases. Unlike primary gastrointestinal tract carcinoid tumors, primary ovarian carcinoid tumors may cause CHD without hepatic metastases, accounting for only 0.3 % of all carcinoid tumors. Only 37 cases of CHD from primary ovarian carcinoid tumors have been reported. We present a case of CHD in which tricuspid valve thickening and shortening led to reduced valve mobility with the resulting severe tricuspid regurgitation. Considering these characteristics of an abnormal tricuspid valve, we suspected CHD, but prosthetic valve replacement was performed without sufficient systemic examination before surgery. Two years after valve replacement, the patient underwent excision of a mass in the lower abdomen, which was diagnosed as an ovarian carcinoid tumor by histopathological examination. The patient has been observed for more than 3 years after tricuspid valve replacement. She has not experienced bioprosthetic valve leaflet degeneration or dysfunction, although it has been reported that bioprosthetic valves may degenerate in patients with carcinoid tumors. Sufficient systemic examinations should be performed to explore the cause of disease.

  1. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    ClinicalTrials.gov

    2017-03-14

    Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  2. Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization.

    PubMed

    Nardo, L G; Ray, D W; Laing, I; Williams, C; McVey, R J; Seif, M W

    2005-10-01

    The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis.

  3. The Crosstalk between Ovarian Cancer Stem Cell Niche and the Tumor Microenvironment

    PubMed Central

    2017-01-01

    Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70–80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression. This interaction can be mediated by cytokines, growth factors, lipids, and/or extracellular vesicles released in the CSC niche. In this review, we will discuss how the interaction between ovarian CSCs and the tumor microenvironment can contribute to the maintenance of the CSC niche and consequently to tumor progression in ovarian cancer. PMID:28819364

  4. The Crosstalk between Ovarian Cancer Stem Cell Niche and the Tumor Microenvironment.

    PubMed

    Varas-Godoy, Manuel; Rice, Gregory; Illanes, Sebastián E

    2017-01-01

    Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70-80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression. This interaction can be mediated by cytokines, growth factors, lipids, and/or extracellular vesicles released in the CSC niche. In this review, we will discuss how the interaction between ovarian CSCs and the tumor microenvironment can contribute to the maintenance of the CSC niche and consequently to tumor progression in ovarian cancer.

  5. Combined Adrenal and Ovarian Venous Sampling to Localize an Androgen Producing Tumor

    SciTech Connect

    Agarwal, Monica D.; Trerotola, Scott O.

    2010-12-15

    A postmenopausal woman presented with hirsutism and elevated serum testosterone levels. A 1-cm adrenal adenoma was noted on computed tomography. Combined adrenal and ovarian venous sampling was performed to localize an androgen producing tumor to the left ovary. The patient underwent a bilateral salpingo-oophrectomy and was spared an unnecessary adrenalectomy.

  6. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    PubMed Central

    Boussios, Stergios; Moschetta, Michele; McLachlan, Jennifer; Banerjee, Susana

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis. PMID:26798532

  7. Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer.

    PubMed

    Graumann, Rebecca; Di Capua, Gabriella A; Oyarzún, Juan E; Vásquez, Marcos A; Liao, Christine; Brañes, Jorge A; Roa, Iván; Casanello, Paola; Corvalán, Alejandro H; Owen, Gareth I; Delgado, Iris; Zangemeister-Wittke, Uwe; Ziegler, Annemarie

    2017-01-01

    Teneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer.

  8. Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer

    PubMed Central

    Graumann, Rebecca; Di Capua, Gabriella A.; Oyarzún, Juan E.; Vásquez, Marcos A.; Liao, Christine; Brañes, Jorge A.; Roa, Iván; Casanello, Paola; Corvalán, Alejandro H.; Owen, Gareth I.; Delgado, Iris; Zangemeister-Wittke, Uwe

    2017-01-01

    Teneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer. PMID:28472127

  9. The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.

    PubMed

    Westerhoff, Maria; Tretiakova, Maria; Hart, John; Gwin, Katja; Liu, Xiuli; Zhou, Ming; Yeh, Matthew M; Antic, Tatjana

    2014-05-01

    FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  11. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors.

    PubMed

    Almeida, Bernardo Gomes de Lacerda; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-12-01

    Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.

  12. [A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

    PubMed

    Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi

    2013-11-01

    A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

  13. [Somatotropic pituitary tumor in a patient with a previous ovarian strumal carcinoid. Report of one case].

    PubMed

    Riedemann, Erick; Rojas, Claudio; Quevedo, Iván

    2004-07-01

    Strumal carcinoid is an unusual form of monodermal ovarian teratoma with thyroid-like follicles mixed with typical carcinoid tumor patterns. We report a 49 years old woman presenting with an acromegaly. At the age of 45, an ovarian strumal carcinoid was excised and at three years of follow up, she complained of finger and feet growth. Laboratory showed an elevated serum IGF-1 and a sella turcica magnetic resonance imaging showed an 8 mm microadenoma. She was subjected to a transphenoidal excision and the pathological study disclosed a solid acidophilic pituitary adenoma. Two months after surgery, there was a significant decrease in serum IGT-I levels.

  14. Recurrent ovarian Sertoli–Leydig cell tumor in a child with Peutz–Jeghers syndrome

    PubMed Central

    Bellfield, Edward J.; Alemzadeh, Ramin

    2016-01-01

    We present a female child with Peutz–Jeghers syndrome (PJS) with a recurrent ovarian Sertoli–Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in a child with PJS to have a recurrent ovarian SLCT. PMID:28101370

  15. In vitro ovarian tumor growth and treatment response dynamics visualized with time-lapse OCT imaging

    PubMed Central

    Evans, Conor L.; Rizvi, Imran; Hasan, Tayyaba; de Boer, Johannes F.

    2010-01-01

    In vitro three-dimensional models for metastatic ovarian cancer have been useful for recapitulating the human disease. These spheroidal tumor cultures, however, can grow in excess of 1 mm in diameter, which are difficult to visualize without suitable imaging technology. Optical coherence tomography (OCT) is an ideal live imaging method for non-perturbatively visualizing these complex systems. OCT enabled detailed observations of the model at both nodular and cellular levels, revealing growth dynamics not previously observed. The development of a time-lapse OCT system, capable of automated, multidimensional acquisition, further provided insights into the growth and chemotherapeutic response of ovarian cancer. PMID:19466138

  16. Contrast-enhanced ultrasound in ovarian tumors – diagnostic parameters: method presentation and initial experience

    PubMed Central

    MAXIM, ANITA-ROXANA; BADEA, RADU; TAMAS, ATILLA; TRAILA, ALEXANDRU

    2013-01-01

    The aim of this paper is to discuss and illustrate the use of contrast-enhanced ultrasound in evaluating ovarian tumors compared to conventional ultrasound, Doppler ultrasound and the histopathological analysis and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. We present the method and initial experience of our center by analyzing the parameters used in contrast-enhanced ultrasound in 6 patients with ovarian tumors of uncertain etiology. For examination we used a Siemens ultrasound machine with dedicated contrast software and the contrast agent SonoVue, Bracco. The patients underwent conventional ultrasound, Doppler ultrasound and i.v. administration of the contrast agent. The parameters studied were: inflow of contrast (rise time), time to peak enhancement, mean transit time. The series of patients is part of an extensive prospective PhD study aimed at elaborating a differential diagnosis protocol for benign versus malignant ovarian tumors, by validating specific parameters for contrast-enhanced ultrasound. Although the method is currently used with great success in gastroenterology, urology and senology, its validation in gynecology is still in the early phases. Taking into consideration that the method is minimally invasive and much less costly that CT/MRI imaging, demonstrating its utility in oncologic gynecology would be a big step in preoperative evaluation of these cases. PMID:26527912

  17. "Borderline" Children.

    ERIC Educational Resources Information Center

    Gualtieri, C. Thomas C.; And Others

    1983-01-01

    The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)

  18. Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

    PubMed Central

    Gupta, Parul; Srivastava, Sanjay K.

    2012-01-01

    Ovarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 µmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer. PMID:22952709

  19. Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients Receiving Platinum Therapy

    PubMed Central

    Wang, Chen; Zimmermann, Michael T.; Chute, Christopher G.; Jiang, Guoqian

    2015-01-01

    The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms. In a previous study, we developed an ADE-based tumor stratification framework (known as ADEStrata) with a case study of breast cancer patients receiving aromatase inhibitors, and demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In this study, we aim to evaluate the ADEStrata framework with a different tumor type and chemotherapy class – ovarian cancer treated with platinum chemotherapeutic drugs. We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156). We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes. PMID:26306234

  20. Stromal Overgrowth in a Brenner Tumor or Ovarian Fibroma With Minor Sex Cord Elements?

    PubMed

    Ross, Julia A; Saglam, Ozlen

    2015-07-01

    Computed tomography obtained as part of a urinary tract assessment in a 68-year-old woman incidentally detected a solid adnexal mass. Bilateral salpingo-oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor.

  1. Differential vimentin expression in ovarian and uterine corpus endometrioid adenocarcinomas: diagnostic utility in distinguishing double primaries from metastatic tumors.

    PubMed

    Desouki, Mohamed M; Kallas, Sarah J; Khabele, Dineo; Crispens, Marta A; Hameed, Omar; Fadare, Oluwole

    2014-05-01

    This study aimed to assess the diagnostic value of vimentin expression in differentiating endometrioid adenocarcinoma of primary uterine corpus and ovarian origin. Immunohistochemical analyses for the expression of vimentin in tumoral epithelial cells were performed on 149 endometrioid adenocarcinomas wherein the primary sites were not in question, including whole tissue sections of 27 carcinomas of uterine corpus origin (and no synchronous ovarian tumor), 7 carcinomas of ovarian origin (and no synchronous uterine corpus tumor) and a tissue microarray (TMA) containing 91 primary uterine corpus and 24 primary ovarian carcinomas. We also assessed 15 cases that synchronously involved the uterine corpus and ovary, 15 cases of metastasis to organs/tissues other than uterine corpus or ovary as well as 7 lymph node metastases. Vimentin was negative in 97% (30/31) of primary ovarian carcinomas. In contrast, 82% (97/118) of primary uterine corpus carcinomas were vimentin-positive. Vimentin expression was discordant in 53% of synchronous tumors. The sensitivity and specificity of negative vimentin staining in predicting an ovarian primary were 97% and 82%, respectively, whereas parallel values for positive vimentin staining in predicting a primary uterine tumor were 82% and 97%, respectively. The pattern of vimentin expression in all cases was maintained in their respective regional lymph nodes and distant metastases. In conclusion, ovarian and uterine corpus endometrioid adenocarcinomas have different patterns of vimentin expression. If validated in larger and/or different data sets, these findings may have diagnostic value in distinguishing metastatic lesions from double primary tumors involving both sites.

  2. Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman

    PubMed Central

    Sood, Neha; Desai, Kaniksha; Chindris, Ana-Maria; Lewis, Jason; Dinh, Tri A.

    2016-01-01

    Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging. PMID:27441075

  3. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    PubMed

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  4. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells

    PubMed Central

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-01-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1-ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma. PMID

  5. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  6. Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4.

    PubMed

    Ren, Yin; Cheung, Hiu Wing; von Maltzhan, Geoffrey; Agrawal, Amit; Cowley, Glenn S; Weir, Barbara A; Boehm, Jesse S; Tamayo, Pablo; Karst, Alison M; Liu, Joyce F; Hirsch, Michelle S; Mesirov, Jill P; Drapkin, Ronny; Root, David E; Lo, Justin; Fogal, Valentina; Ruoslahti, Erkki; Hahn, William C; Bhatia, Sangeeta N

    2012-08-15

    The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance because many of these targets are not amenable to manipulation by small molecules or antibodies. RNA interference provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) that comprised small interfering RNA (siRNA) complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We used TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor-bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets.

  7. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  8. Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer target ID4

    PubMed Central

    Ren, Yin; Cheung, Hiu Wing; von Maltzhan, Geoffrey; Agrawal, Amit; Cowley, Glenn S.; Weir, Barbara A.; Boehm, Jesse S.; Tamayo, Pablo; Karst, Alison M.; Liu, Joyce F.; Hirsch, Michelle S.; Mesirov, Jill P.; Drapkin, Ronny; Root, David E.; Lo, Justin; Fogal, Valentina; Ruoslahti, Erkki; Hahn, William C.; Bhatia, Sangeeta N.

    2013-01-01

    The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance, because many of these targets are not amenable to manipulation by small molecules or antibodies. RNAi provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) comprised of siRNA complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We employed TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor-bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers, but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets. PMID:22896676

  9. Stromal p16 expression is significantly increased in malignant ovarian neoplasms

    PubMed Central

    Yoon, Nara; Yoon, Gun; Park, Cheol Keun; Kim, Hyun-Soo

    2016-01-01

    Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results. PMID:27572321

  10. Stromal p16 expression is significantly increased in malignant ovarian neoplasms.

    PubMed

    Yoon, Nara; Yoon, Gun; Park, Cheol Keun; Kim, Hyun-Soo

    2016-10-04

    Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results.

  11. A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-02-27

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Recurrent Ovarian Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma12

    PubMed Central

    Moreno-Smith, Myrthala; Lee, Sun Joo; Lu, Chunhua; Nagaraja, Archana S; He, Guangan; Rupaimoole, Rajesha; Han, Hee Dong; Jennings, Nicholas B; Roh, Ju-Won; Nishimura, Masato; Kang, Yu; Allen, Julie K; Armaiz, Guillermo N; Matsuo, Koji; Shahzad, Mian M K; Bottsford-Miller, Justin; Langley, Robert R; Cole, Steve W; Lutgendorf, Susan K; Siddik, Zahid H; Sood, Anil K

    2013-01-01

    Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA), an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2), our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP) levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth. PMID:23633922

  13. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    PubMed

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  14. Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.

    PubMed

    Trillsch, F; Mahner, S; Woelber, L; Vettorazzi, E; Reuss, A; Ewald-Riegler, N; de Gregorio, N; Fotopoulou, C; Schmalfeldt, B; Burges, A; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H G; Hellriegel, M; Wimberger, P; Baumann, K; Keyver-Paik, M D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Kommoss, F; Hauptmann, S; du Bois, A

    2014-07-01

    Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be

  15. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer

    PubMed Central

    Wen, Wei; Liang, Wei; Wu, Jun; Kowolik, Claudia M.; Buettner, Ralf; Scuto, Anna; Hsieh, Meng-Yin; Hong, Hao; Brown, Christine E.; Forman, Stephen J.; Horne, David; Morgan, Robert; Wakabayashi, Mark; Dellinger, Thanh H.; Han, Ernest S.; Yim, John H.; Jove, Richard

    2015-01-01

    JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in ovarian cancer patients. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine-cytokine loop involving the IL-6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL-6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL-6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer. PMID:25319391

  16. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer.

    PubMed

    Wen, Wei; Liang, Wei; Wu, Jun; Kowolik, Claudia M; Buettner, Ralf; Scuto, Anna; Hsieh, Meng-Yin; Hong, Hao; Brown, Christine E; Forman, Stephen J; Horne, David; Morgan, Robert; Wakabayashi, Mark; Dellinger, Thanh H; Han, Ernest S; Yim, John H; Jove, Richard

    2014-12-01

    JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in patients with ovarian cancer. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late-stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine cytokine loop involving the IL6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination, and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small-molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer.

  17. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway.

    PubMed

    Chen, Jianchu; Chen, Allen Y; Huang, Haizhi; Ye, Xingqian; Rollyson, William D; Perry, Haley E; Brown, Kathleen C; Rojanasakul, Yon; Rankin, Gary O; Dasgupta, Piyali; Chen, Yi Charlie

    2015-01-01

    Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at <40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers.

  18. Anti-tumor effects of osthole on ovarian cancer cells in vitro.

    PubMed

    Jiang, Guoqiang; Liu, Jia; Ren, Baoyin; Tang, Yawei; Owusu, Lawrence; Li, Man; Zhang, Jing; Liu, Likun; Li, Weiling

    2016-12-04

    Cnidium monnieri (L.) Cusson is a commonly used traditional Chinese medicine to treat gynecological disease in some countries. Osthole, an active O-methylated coumadin isolated from Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-seizure and anti-inflammatory effects. However, the anti-tumor mechanism of osthole is not well known. Here, we show that osthole inhibited the proliferation and migration of two widely used ovarian cancer cell lines, A2780 and OV2008 cells, in a dose-dependent manner. The study investigated the molecular mechanisms underlying ovarian cancer cells proliferation, apoptosis, cell cycle arrest and migration triggered by osthole. Ovarian cancer cell lines A2780, OV2008 and normal ovarian cell line IOSE80 were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry assays were performed to confirm apoptosis and cell cycle. We employed wound healing and transwell assays to delineate invasive and migratory potential triggered by osthole. MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with osthole without effect on normal ovarian cells. Flow cytometric analysis revealed that osthole suppressed cells proliferation by promoting G2/M arrest and inducing apoptosis. The underlying mechanisms involved were regulation of the relative apoptotic protein Bcl-2, Bax and Caspase 3/9. In addition, wound healing and transwell assays revealed that the migratory potential and activity of matrix metalloproteinase MMP-2 and MMP-9 were markedly inhibited when cells were exposed to osthole. Our findings suggested that osthole has the potential to be used in novel anti-cancer therapeutic formulations for ovarian cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway

    PubMed Central

    CHEN, JIANCHU; CHEN, ALLEN Y.; HUANG, HAIZHI; YE, XINGQIAN; ROLLYSON, WILLIAM D.; PERRY, HALEY E.; BROWN, KATHLEEN C.; ROJANASAKUL, YON; RANKIN, GARY O.; DASGUPTA, PIYALI; CHEN, YI CHARLIE

    2015-01-01

    Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at <40 μM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers. PMID:25845666

  20. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    ClinicalTrials.gov

    2015-10-29

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  1. Surveillance of the tumor mutanome by T cells during progression from primary to recurrent ovarian cancer.

    PubMed

    Wick, Darin A; Webb, John R; Nielsen, Julie S; Martin, Spencer D; Kroeger, David R; Milne, Katy; Castellarin, Mauro; Twumasi-Boateng, Kwame; Watson, Peter H; Holt, Rob A; Nelson, Brad H

    2014-03-01

    Cancers accumulate mutations over time, each of which brings the potential for recognition by the immune system. We evaluated T-cell recognition of the tumor mutanome in patients with ovarian cancer undergoing standard treatment. Tumor-associated T cells from 3 patients with ovarian cancer were assessed by ELISPOT for recognition of nonsynonymous mutations identified by whole exome sequencing of autologous tumor. The relative levels of mutations and responding T cells were monitored in serial tumor samples collected at primary surgery and first and second recurrence. The vast majority of mutations (78/79) were not recognized by tumor-associated T cells; however, a highly specific CD8(+) T-cell response to the mutation hydroxysteroid dehydrogenase-like protein 1 (HSDL1)(L25V) was detected in one patient. In the primary tumor, the HSDL1(L25V) mutation had low prevalence and expression, and a corresponding T-cell response was undetectable. At first recurrence, there was a striking increase in the abundance of the mutation and corresponding MHC class I epitope, and this was accompanied by the emergence of the HSDL1(L25V)-specific CD8(+) T-cell response. At second recurrence, the HSDL1(L25V) mutation and epitope continued to be expressed; however, the corresponding T-cell response was no longer detectable. The immune system can respond to the evolving ovarian cancer genome. However, the T-cell response detected here was rare, was transient, and ultimately failed to prevent disease progression. These findings reveal the limitations of spontaneous tumor immunity in the setting of standard treatments and suggest a high degree of ignorance of tumor mutations that could potentially be reversed by immunotherapy. ©2013 AACR

  2. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    PubMed

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  3. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.

    PubMed

    Henry, C E; Emmanuel, C; Lambie, N; Loo, C; Kan, B; Kennedy, C J; de Fazio, A; Hacker, N F; Ford, C E

    2017-06-01

    The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. In vivo bioengineered ovarian tumors based on collagen, matrigel, alginate and agarose hydrogels: a comparative study.

    PubMed

    Zheng, Li; Hu, Xuefeng; Huang, Yuanjie; Xu, Guojie; Yang, Jinsong; Li, Li

    2015-01-29

    Scaffold-based tumor engineering is rapidly evolving the study of cancer progression. However, the effects of scaffolds and environment on tumor formation have seldom been investigated. In this study, four types of injectable hydrogels, namely, collagen type I, Matrigel, alginate and agarose gels, were loaded with human ovarian cancer SKOV3 cells and then injected into nude mice subcutaneously. The growth of the tumors in vitro was also investigated. After four weeks, the specimens were harvested and analyzed. We found that tumor formation by SKOV3 cells was best supported by collagen, followed by Matrigel, alginate, control (without scaffold) and agarose in vivo. The collagen I group exhibited a larger tumor volume with increased neovascularization and increased necrosis compared with the other materials. Further, increased MMP activity, upregulated expression of laminin and fibronectin and higher levels of HIF-1α and VEGF-A in the collagen group revealed that the engineered tumor is closer to human ovarian carcinoma. In order, collagen, Matrigel, alginate, control (without scaffold) and agarose exhibited decreases in tumor formation. All evidence indicated that the in vivo engineered tumor is scaffold-dependent. Bioactive hydrogels are superior to inert hydrogels at promoting tumor regeneration. In particular, biomimetic hydrogels are advantageous because they provide a microenvironment that mimics the ECM of natural tumors. On the other hand, typical features of cancer cells and the expression of genes related to cancer malignancy were far less similar to the natural tumor in vitro, which indicated the importance of culture environment in vivo. Superior to the in vitro culture, nude mice can be considered satisfactory in vivo 'bioreactors' for the screening of favorable cell vehicles for tumor engineering in vitro.

  5. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells

    PubMed Central

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M.; Chen, Maoshan; Findlay, Jock K.; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  6. Ovarian malignant mixed mesodermal tumor with neuroectodermal differentiation: a multifaceted evaluation.

    PubMed

    Mott, Ryan T; Murphy, Bettina A; Geisinger, Kim R

    2010-05-01

    Malignant mixed mesodermal tumors (MMMTs) of the ovary are rare, highly aggressive neoplasms that arise most commonly in postmenopausal women. Histologically, they consist of a mixed population of malignant epithelial and mesenchymal elements. Neuroectodermal differentiation in ovarian MMMTs is exceedingly uncommon, with only a few case reports in the literature. We present a case of an ovarian MMMT with neuroectodermal differentiation in a 78-year-old female patient. Histologically, the tumor was composed of epithelial, mesenchymal, and neuroectodermal elements. The neuroectodermal component was predominantly that of a medulloepithelioma, with scattered areas displaying features of an anaplastic astrocytoma, including rare ganglion cell differentiation. The neuroectodermal component showed immunoreactivity for glial fibrillary acidic protein, synaptophysin, and S100 protein. Ultrastructurally, the neuroectodermal component was populated by cells with irregular nuclei, finely dispersed chromatin, rudimentary cell junctions, and a delicate basement membrane, all of which have been described in medulloepitheliomas. DNA ploidy analysis was also performed on the various components of the tumor and compared with 3 additional cases of MMMT without neuroectodermal differentiation and 2 ovarian immature teratomas. Our findings suggest that the neuroectodermal component may arise from a separate clone or at least evolves at an earlier stage of tumor development.

  7. RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors

    PubMed Central

    Winter, Andrew G.; Sourvinos, George; Allison, Simon J.; Tosh, Kerrie; Scott, Pamela H.; Spandidos, Demetrios A.; White, Robert J.

    2000-01-01

    Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is overexpressed in tumors. This factor, TFIIIC2, is a histone acetyltransferase that is required for synthesis of most pol III products, including tRNA and 5S rRNA. TFIIIC2 is a complex of five polypeptides, and mRNAs encoding each of these subunits are overexpressed in human ovarian carcinomas; this may explain the elevated TFIIIC2 activity that is found consistently in the tumors. Deregulation in these cancers is unlikely to be a secondary response to rapid proliferation, because there is little or no change in TFIIIC2 mRNA levels when actively cycling cells are compared with growth-arrested cells in culture. Using purified factors, we show that raising the level of TFIIIC2 is sufficient to stimulate pol III transcription in ovarian cell extracts. The data suggest that overexpression of TFIIIC2 contributes to the abnormal abundance of pol III transcripts in ovarian tumors. PMID:11058163

  8. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

    PubMed

    Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

    2015-07-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

  9. Contrast-Enhanced Ultrasonography in Differential Diagnosis of Benign and Malignant Ovarian Tumors

    PubMed Central

    Qiao, Jing-Jing; Yu, Jing; Yu, Zhe; Li, Na; Song, Chen; Li, Man

    2015-01-01

    Objective To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of benign and malignant ovarian tumors. Methods The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe), sensitivity (Sen), positive and negative likelihood ratios (LR+/LR−), and diagnostic odds ratio (DOR) and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). Results Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign). Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98); the summary Spe was 0.91 (95%CI = 0.86∼0.94); the pooled LR+ was 10.63 (95%CI = 6.59∼17.17); the pooled LR− was 0.04 (95%CI = 0.02∼0.09); and the pooled DOR was 241.04 (95% CI = 92.61∼627.37). The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00). Lastly, publication bias was not detected (t = −0.52, P = 0.626) in the meta-analysis. Conclusions Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease. PMID:25764442

  10. Contrast-enhanced ultrasonography in differential diagnosis of benign and malignant ovarian tumors.

    PubMed

    Qiao, Jing-Jing; Yu, Jing; Yu, Zhe; Li, Na; Song, Chen; Li, Man

    2015-01-01

    To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of benign and malignant ovarian tumors. The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe), sensitivity (Sen), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratio (DOR) and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign). Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98); the summary Spe was 0.91 (95%CI = 0.86∼0.94); the pooled LR+ was 10.63 (95%CI = 6.59∼17.17); the pooled LR- was 0.04 (95%CI = 0.02∼0.09); and the pooled DOR was 241.04 (95% CI = 92.61∼627.37). The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00). Lastly, publication bias was not detected (t = -0.52, P = 0.626) in the meta-analysis. Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease.

  11. Expression of the tumor suppressor gene p16, and lymph node metastasis in patients with ovarian cancer.

    PubMed

    Wang, Hongyan; Zheng, Jingfang; Li, Qiang; Zhou, Min; Ai, Dongmei; Zhang, Hui

    2017-10-01

    This study examined the relationship between the expression of p16, a tumor suppressor gene, and lymph node metastasis, as well as patient prognosis, in cases with ovarian cancer. SKOV-3, an ovarian cancer cell line, and IOSE80, a normal human ovarian cell line, were selected for testing. Western blot analysis was used to detect the p16 expression in ovarian cell culture samples. In the study, 20 cases with normal ovarian tissue and 64 cases with ovarian cancer tissue, including 38 cases with lymph node metastasis and 26 cases without lymph node metastasis, were also selected for testing. Immunohistochemical techniques were used to detect the expression of p16 protein in ovarian tissue samples. The influence of p16 protein on SKOV-3 cell invasion ability was studied using p16 gene high-expression vector transfection. Clinical and prognosis data were summarized and the influence of p16 on patient prognosis was analyzed through Kaplan-Meier single-factor survival analysis. The results showed that p16 expression in SKOV-3 was decreased significantly compared with that in IOSE80. The positive rate of p16 protein expression in ovarian cancer tissue was notably decreased compared with that in normal ovarian tissue. The positive rate of p16 protein expression in ovarian cancer tissue of patients with lymph node metastasis was significantly decreased compared with that of patients without lymph node metastasis. Therefore, transfection of the p16 gene significantly inhibited the protein expression and invasion ability of p16 in SKOV-3. Correlation analyses between p16 and survival prognosis demonstrated that lower expression of p16 was negatively correlated with the prognosis of patients with ovarian cancer. Overall, the abnormal expression of p16 in ovarian cancer is associated with an increased invasion ability of ovarian cancer and the lower expression of p16 in tissue samples indicates a poor prognosis in patients with ovarian cancer.

  12. Expression of the tumor suppressor gene p16, and lymph node metastasis in patients with ovarian cancer

    PubMed Central

    Wang, Hongyan; Zheng, Jingfang; Li, Qiang; Zhou, Min; Ai, Dongmei; Zhang, Hui

    2017-01-01

    This study examined the relationship between the expression of p16, a tumor suppressor gene, and lymph node metastasis, as well as patient prognosis, in cases with ovarian cancer. SKOV-3, an ovarian cancer cell line, and IOSE80, a normal human ovarian cell line, were selected for testing. Western blot analysis was used to detect the p16 expression in ovarian cell culture samples. In the study, 20 cases with normal ovarian tissue and 64 cases with ovarian cancer tissue, including 38 cases with lymph node metastasis and 26 cases without lymph node metastasis, were also selected for testing. Immunohistochemical techniques were used to detect the expression of p16 protein in ovarian tissue samples. The influence of p16 protein on SKOV-3 cell invasion ability was studied using p16 gene high-expression vector transfection. Clinical and prognosis data were summarized and the influence of p16 on patient prognosis was analyzed through Kaplan-Meier single-factor survival analysis. The results showed that p16 expression in SKOV-3 was decreased significantly compared with that in IOSE80. The positive rate of p16 protein expression in ovarian cancer tissue was notably decreased compared with that in normal ovarian tissue. The positive rate of p16 protein expression in ovarian cancer tissue of patients with lymph node metastasis was significantly decreased compared with that of patients without lymph node metastasis. Therefore, transfection of the p16 gene significantly inhibited the protein expression and invasion ability of p16 in SKOV-3. Correlation analyses between p16 and survival prognosis demonstrated that lower expression of p16 was negatively correlated with the prognosis of patients with ovarian cancer. Overall, the abnormal expression of p16 in ovarian cancer is associated with an increased invasion ability of ovarian cancer and the lower expression of p16 in tissue samples indicates a poor prognosis in patients with ovarian cancer. PMID:28943963

  13. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer.

    PubMed

    Swisher, Elizabeth M; Wollan, Melissa; Mahtani, Sarita M; Willner, Julia B; Garcia, Rochelle; Goff, Barbara A; King, Mary-Claire

    2005-09-01

    Free tumor DNA in body fluids may be an important biomarker. We tested whether tumor-specific mutated p53 DNA can be detected in blood and peritoneal fluid from women with epithelial ovarian cancer. Sequencing of tumor DNA identified somatic p53 mutations. Free DNA from matched blood or peritoneal fluid was evaluated for the tumor-specific p53 mutation using a ligase detection reaction. Sixty-nine of 137 tumors (50%) had p53 mutations. Plasma or serum from 21 (30%) of the 69 informative cases contained the tumor-specific p53 mutation. Circulating tumor was an independent predictor of decreased survival in multivariate analysis (P=.02). We detected tumor DNA in peritoneal fluid in 28 of 30 (93%) cases, including all 6 cases with negative cytology. One third of women with ovarian cancer have circulating tumor DNA and an associated reduced survival. Free tumor DNA can be detected in the majority of peritoneal fluid samples.

  14. A Tete – a – tete of benign, borderline and malignant fibrohistiocytic tumor

    PubMed Central

    M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa

    2016-01-01

    Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980

  15. Eudaimonic Well-Being and Tumor Norepinephrine in Epithelial Ovarian Cancer Patients

    PubMed Central

    Davis, Lauren Z.; Slavich, George M.; Thaker, Premal H.; Goodheart, Michael J.; Bender, David; Dahmoush, Laila; Farley, Donna; Markon, Kristian; Penedo, Frank J.; Lubaroff, David M.; Cole, Steve W.; Sood, Anil K.; Lutgendorf, Susan K.

    2015-01-01

    Background The impact of psychological well-being on physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, we examined how two different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in ovarian cancer patients. Methods Women with suspected ovarian cancer (N=365) completed psychosocial assessments pre-surgery and clinical information was obtained from medical records. Study inclusion was confirmed following histological diagnosis. Tumor NE was measured in frozen tissue samples using HPLC with electrochemical detection. We employed confirmatory factor analysis to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling (SEM) to examine associations between these factors and tumor NE. Results Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (i.e., compared to unitary or 2-factor models) (RMSEA=.048, CFI=.982, SRMR=.035). SEM analyses that included physical well-being, stage, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates had good model fit (RMSEA=.052, CFI=.955, SRMR=.036) and showed that eudaimonic well-being was related to lower tumor NE (β=−.24, p=.045). In contrast, we found no effects for positive affect or psychological distress. Conclusion Eudaimonic well-being is associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well-being may improve both psychological and physiologic resilience in ovarian cancer patients. PMID:26096769

  16. Bilateral Ovarian Krukenberg Tumor in a Full-Term Pregnancy

    PubMed Central

    Dueñas-García, Omar Felipe; Diaz-Sotomayor, Maricela; Chanana, Charu

    2011-01-01

    Objective. Krukenberg tumors in pregnancy are very rare and their management can present a dilemma for the obstetrician gynecologist. Case Report. We present the case of a G3P2002 who presented to us and the 38 weeks gestation with bilateral massive Krukenberg tumors. Despite at surgery and chemotherapy she died 3 months postpartum. Conclusion. Early detection followed by surgery and chemotherapy could possibly result in a favorable outcome with such patients. PMID:21637363

  17. Ovarian tumor in a 12-year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome.

    PubMed

    Hunold, Andrea; Alzen, Gerhard; Wudy, Stefan A; Bluetters-Sawatzki, Renate; Landmann, Eva; Reiter, Alfred; Wagner, Hans-Joachim

    2009-05-01

    We report a 12-year-old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L-thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient.

  18. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report

    PubMed Central

    Agrawal, Nidhi; Vardhan, Harsh; Khokhar, Singh; Rai, Naresh; Saxena, Rajeev; Riyaz, Shahida

    2015-01-01

    Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI) are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings. PMID:26811582

  19. Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma.

    PubMed

    Dorfman, H D; Weiss, S W

    1984-08-01

    A series of 102 benign osteoblastic tumors of multiple skeletal sites was reviewed, and on the basis of their clinical, radiologic, and pathologic features they were classified into three diagnostic categories: osteoid osteoma, osteoblastoma, and aggressive osteoblastoma. A historic review of the development of the nomenclature of benign osteoblastic tumors, with special emphasis on the evolving concept of aggressive and malignant behavior, is presented. Histologic criteria for the recognition of aggressive osteoblastoma are presented and illustrated in connection with the 15 cases so classified in the present series. The differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma is discussed. In defining the problem of differentiating locally aggressive osteoblastic lesions from potentially metastasizing tumors, the authors propose that four categories of these osteoblastic tumors can be defined: (1) Innocuous-appearing low-grade osteosarcomas that resemble osteoblastomas histologically. This mimicry accounts for most errors in diagnosis. (2) Rare osteoblastomas that have undergone spontaneous transformation into osteosarcomas. (3) Very rare, clinically and radiologically typical osteoblastomas that show pseudosarcomatous histologic features but pursue a benign course. (4) Locally aggressive osteoblastomas that are likely to recur, do not metastasize, and show characteristic and recognizable histologic features.

  20. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    PubMed Central

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  1. High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors

    PubMed Central

    Haverty, Peter M; Hon, Lawrence S; Kaminker, Joshua S; Chant, John; Zhang, Zemin

    2009-01-01

    Background DNA copy number alterations are frequently observed in ovarian cancer, but it remains a challenge to identify the most relevant alterations and the specific causal genes in those regions. Methods We obtained high-resolution 500K SNP array data for 52 ovarian tumors and identified the most statistically significant minimal genomic regions with the most prevalent and highest-level copy number alterations (recurrent CNAs). Within a region of recurrent CNA, comparison of expression levels in tumors with a given CNA to tumors lacking that CNA and to whole normal ovary samples was used to select genes with CNA-specific expression patterns. A public expression array data set of laser capture micro-dissected (LCM) non-malignant fallopian tube epithelia and LCM ovarian serous adenocarcinoma was used to evaluate the effect of cell-type mixture biases. Results Fourteen recurrent deletions were detected on chromosomes 4, 6, 9, 12, 13, 15, 16, 17, 18, 22 and most prevalently on X and 8. Copy number and expression data suggest several apoptosis mediators as candidate drivers of the 8p deletions. Sixteen recurrent gains were identified on chromosomes 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, and 20, with the most prevalent gains localized to 8q and 3q. Within the 8q amplicon, PVT1, but not MYC, was strongly over-expressed relative to tumors lacking this CNA and showed over-expression relative to normal ovary. Likewise, the cell polarity regulators PRKCI and ECT2 were identified as putative drivers of two distinct amplicons on 3q. Co-occurrence analyses suggested potential synergistic or antagonistic relationships between recurrent CNAs. Genes within regions of recurrent CNA showed an enrichment of Cancer Census genes, particularly when filtered for CNA-specific expression. Conclusion These analyses provide detailed views of ovarian cancer genomic changes and highlight the benefits of using multiple reference sample types for the evaluation of CNA-specific expression changes

  2. Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors.

    PubMed

    Leung, Dilys T H; Fuller, Peter J; Chu, Simon

    2016-03-01

    Granulosa cell tumors (GCT) are unique sex-cord stromal tumors which account for ∼ 8% of all ovarian malignancies. They exhibit morphological, biochemical and hormonal features similar to proliferating granulosa cells of the preovulatory follicle, including estrogen and inhibin synthesis. A somatic missense mutation in the forkhead box L2 (FOXL2) gene (C134W) is unique to adult GCT, and absent in other ovarian cancers. FOXL2 is a transcription factor that plays a critical role in ovarian function, in particular, proliferation and differentiation of granulosa cells. The molecular mechanisms underlying the pathogenicity of the mutant FOXL2 remain unresolved. Here we review the molecular alterations known to be associated with mutant FOXL2 and the potential signaling implications. Several studies suggest that dysregulated FOXL2 function may alter cell cycle progression and apoptosis. Further insights into the molecular mechanism of GCT pathophysiology may identify therapeutic targets for the treatment of these tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Characterization of a common antigen of colorectal and mucinous ovarian tumors, COTA.

    PubMed

    Pant, K D; Zamora, P O; Rhodes, B A; Sachatello, C R; Hagihara, P F; Griffen, W O; van Nagell, J R; Fulks, R; Ram, M D

    1984-01-01

    A new colon cancer antigen is reported. It is designated as COTA, Colon-Ovarian Tumor Antigen, because it is found in mucins produced by both tissues during malignancy. The new antigen was identified by making antibodies against human colon cancer tissue in goats. The antisera were exhaustively absorbed with lyophilized extracts of normal colon, lung, liver, spleen, kidney, plasma, and the well-known colon tumor antigen, carcinoembryonic antigen (CEA). The new antigen was identified by immunodiffusion. Studies of 28 malignant tissue extracts, 10 ovarian adenocarcinoma cyst fluids, 43 normal tissues, and 5 plasma samples revealed that this antigen is found only in colon tumors and mucinous ovarian adenocarcinomas. The antigen was not detected in serous adenocarcinoma of the ovaries, extracts of adenocarcinoma of lung, breast, kidney or stomach nor in the extracts of normal tissues. Other tests show that this antigen is not CEA, Ca 19-9, or CSAp. It is stable to heating at 65 degrees for 5 minutes; it elutes from an ion exchange matrix (DEAE) with 0.3-0.5M NaCl; it migrates to the alpha-2 region on immunoelectrophoresis; and its size, by exclusion chromatography on Sepharose 4B, is 3-15 million daltons. Anti-COTA stains colon cancer tissue sections indicating that COTA is present in goblet-cell mucin.

  4. [Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis].

    PubMed

    Castiblanco G, Adriana; Pires N, Yumay; Wistuba O, Ignacio; Riquelme S, Erick; Andrade M, Leonardo; Corvalán R, Alejandro

    2006-03-01

    Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p <0.005). There was a histological correlation between EA and a higher cellular proliferation index. PTEN was negative in 5 of 15 EN, 9 of 15 EA and 30 of 37 CE/CC. There was a correlation between LOH and loss of PTEN protein in EN, EA and ET (60%). Negative expression on PTEN in EN; EA; ET and CE/CC is a manifestation of the inactivation of this gene. The mechanisms that cause this inactivation, must be elucidated.

  5. Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors

    PubMed Central

    Fan, Xinhua; Zhang, Hongbin; Meng, Shuang; Zhang, Jing; Zhang, Chuge

    2015-01-01

    Objective: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating malignancies from benign ovarian tumors and a meta-analysis to further confirm our results on DW-MRI. Methods: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta-analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 ± 0.269×10-3 mm2/s vs. 0.878 ± 0.246×10-3 mm2/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. Conclusions: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID:26884905

  6. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

    PubMed Central

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-01-01

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797

  7. c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian carcinoma (SCCOHT) populations.

    PubMed

    Otte, Anna; Rauprich, Finn; von der Ohe, Juliane; Yang, Yuanyuan; Kommoss, Friedrich; Feuerhake, Friedrich; Hillemanns, Peter; Hass, Ralf

    2015-10-13

    A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian carcinoma demonstrated constitutive chemokine and growth factor production including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested an autocrine growth mechanism. Expression of c-Met was also observed at low levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)). Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a heterogeneous distribution between undetectable levels and 80%. Further characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including CD90 and EpCAM demonstrated similar patterns with differences to the ovarian adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42 MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50 of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited an approximately 10-fold and 5-fold reduced tumor size following systemic application of foretinib, respectively. Furthermore, foretinib-treated tumors revealed a significantly reduced vascularization and little if any c-Met-mediated signal transduction. Similar findings of reduced proliferative capacity and declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT-1 cells demonstrating that in vivo inhibition of these pathways contributed to an attenuation of SCCOHT tumor growth.

  8. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells

    PubMed Central

    Stewart, Jocelyn M.; Shaw, Patricia A.; Gedye, Craig; Bernardini, Marcus Q.; Neel, Benjamin G.; Ailles, Laurie E.

    2011-01-01

    The cancer stem cell (CSC) model proposes that tumors have a hierarchical organization in which only some cells indefinitely self-renew and thereby sustain tumor growth. In addition, the CSC model requires that tumor-initiating cells (TICs) be prospectively isolatable on the basis of their phenotype. Previous studies have suggested that serous ovarian cancer (SOC) conforms to the CSC model, but these used arguably nonfidelitous immortalized cell lines, cultured primary cells, or passaged xenografts as the source of tumor cells. We developed a robust assay for quantifying TICs from primary SOC. Using this assay, we find that TICs are rare when assayed in either NOD/SCID or NOD/SCID/IL2Rγ−/− (NSG) mice. TIC frequency (TICf) varies substantially between patients, although it is similar in primary ovarian masses and omental metastases, suggesting that TICf is an intrinsic property of ovarian tumors. CD133 marks all TICs from several primary SOC cases. However, in other cases, substantial TIC activity is found in both the CD133+ and CD133− fractions, whereas still other cases have exclusively CD133− TICs. Furthermore, the TIC phenotype can change in xenografts: primary tumors in which all TICs are CD133+ can give rise to xenografts that contain substantial numbers of CD133− TICs. Our results highlight the need for quantitative rigor in the evaluation of TICs and for caution when using passaged xenografts for such studies. Furthermore, although our data suggest that SOC conforms to the CSC hypothesis, the heterogeneity of the TIC phenotype may complicate its clinical application. PMID:21451132

  9. Resolution of right-sided heart failure symptoms after resection of a primary ovarian carcinoid tumor.

    PubMed

    Goldman, Todd; Adamson, Kathi; Yang, Eugene

    2014-10-01

    Carcinoid tumors are rare neuroendocrine malignancies that typically originate from the gastrointestinal tract. Patients who are diagnosed with carcinoid heart disease generally have poor prognoses because of advanced metastases during staging and few therapeutic options. We present the case of a 61-year-old woman with right-sided heart failure, secondary to carcinoid heart disease caused by a primary ovarian carcinoid tumor. After undergoing surgical resection of the left ovary and fallopian tube, the patient experienced complete resolution of her heart failure symptoms. In addition to the patient's case, we discuss the diagnosis, nature, and treatment of this rare condition.

  10. Ovarian cancer survival by tumor dominance, a surrogate for site of origin

    PubMed Central

    Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne

    2015-01-01

    Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796

  11. Granular Cell Tumor Within an Ovarian Mature Cystic Teratoma: Report of a Unique Case and Review of the Literature.

    PubMed

    Borak, Samuel G; Ross, John R; Bell, Walter C

    2017-09-01

    Granular cell tumors involving the female reproductive tract are rare, with only a small number of cases described. Of the reported cases, none are documented within an ovarian mature cystic teratoma (MCT). This report documents a case of a granular cell tumor, incidentally discovered within an ovarian MCT in a 50-yr-old woman undergoing a supracervical hysterectomy and left salpingo-oophorectomy. Although malignant transformation and other secondary ovarian neoplasms in MCT have been well documented, synchronous nonovarian benign neoplasms are reported much less frequently. The histogenesis of secondary tumors arising in MCT is incompletely understood, and the current case provides additional insight, especially pertaining to schwannian and neuroectodermal tumors arising in this setting. The current case, to the best of our knowledge, represents the first report of a granular cell tumor involving a mature teratoma of any site, with the diagnosis being supported by morphologic and immunohistochemical staining characteristics.

  12. Differential diagnosis of ovarian tumors based primarily on their patterns and cell types.

    PubMed

    Young, R H; Scully, R E

    2001-08-01

    The differential diagnosis of ovarian tumors is reviewed based on their patterns and cell types. This approach, which differs from the standard textbook discussion of each neoplasm as an entity, has practical value as differential diagnosis depends largely on the pattern or patterns and cell type or types of tumors. Awareness of the broad range of lesions that may exhibit particular patterns or contain one or more cell types is crucial in formulating a differential diagnosis. The following patterns are considered: moderate-to-large-glandular and hollow-tubular; solid tubular and pseudotubular; cords and ribbons; insular; trabecular; slit-like and reticular spaces; microglandular and microfollicular; macrofollicular and pseudomacrofollicular; papillary; diffuse; fibromatous-thecomatous; and biphasic and pseudobiphasic. The following cell types are considered: small round cells; spindle cells; mucinous cells, comprising columnar, goblet cell and signet ring cell subtypes; clear cells; hobnail cells; oxyphil cells; and transitional cells. The morphologic diversity of ovarian tumors poses many challenges; knowledge of the occurrence and frequency of these patterns and cell types in various tumors and tumor-like lesions is of paramount diagnostic importance. A specific diagnosis can usually be made by evaluating routinely stained slides, but much less often, special staining, immunohistochemical staining or, very rarely, ultrastructural examination is also required. Finally, clinical data, operative findings, and gross features of the lesions may provide important, and at times decisive diagnostic clues.

  13. CCL18 from tumor-cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway.

    PubMed

    Wang, Qi; Tang, Yong; Yu, Hongjing; Yin, Qiaoyun; Li, Mengdi; Shi, Lijun; Zhang, Wei; Li, Danrong; Li, Li

    2016-11-01

    CCL18 is a chemotactic cytokine involved in the pathogenesis and progression of various disorders, including cancer. Previously, our results showed high levels of CCL18 in the serum of epithelial ovarian carcinoma patients suggesting its potential as a circulating biomarker. In this study, we determined that CCL18 expression was up-regulated in ovarian carcinoma compared with adjacent tissue and was expressed in carcinoma cells in the tumor and not in normal ovarian epithelial cells by laser capture microdissection coupled with real-time RT-PCR. Moreover, correlation analysis showed that the CCL18 level was positively correlated with the metastasis of patients with ovarian cancer. Survival analysis also revealed that an increased level of CCL18 was associated with worse survival time in ovarian cancer patients. Over-expression of CCL18 led to enhanced migration and invasion of the Skov3 ovarian cancer cell line in vitro and in vivo. Finally, proteomics analysis demonstrated that CCL18-mediated ovarian cancer invasiveness was strongly correlated with the mTORC2 pathway. These findings suggest that the CCL18 chemokine has an important role in chemokine-mediated tumor metastasis, and may serve as a potential predictor for poor survival outcomes for ovarian cancer. © 2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc. © 2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

  14. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  15. Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  16. TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  17. Ovarian malignant mixed mullerian tumor with primitive neuroectodermal differentiation: case report with review of the literature.

    PubMed

    Nasser, Haitham; Morris, Robert T; Fathallah, Lamia

    2011-03-15

    Ovarian malignant mixed mullarian tumor (OMMMT) is a rare and aggressive tumor of the female genital tract, occurring mainly in elderly women. Stage of disease is the most important predictor for survival with no prognostic effect, yet, of heterologous elements. Rare case reports described the peculiar presence of primitive neuroectodermal tissue among other heterologous elements in these tumors. Attractive designations, such as teratoid carcinosarcoma, were set by some authors to describe this subset of lesions, where it was considered a primary neuroectodermal tumor capable of multilineage differentiation. We here report a case of OMMMT in an elderly woman with focal primitive neuroectodermal differentiation as the sole heterologous element, and review the controversy on this topic in the literature.

  18. [Virilization caused by an ovarian tumor. Report of one case].

    PubMed

    Salman M, Patricio; Cuello F, Mauricio; Kolbach, Marianne; Gejman, Roger; Arteaga U, Eugenio

    2011-08-01

    We report a 76-year-old woman with a virilization syndrome characterized by progressive androgenic alopecia, clitoris enlargement and hirsutism predominating in the face. Plasma testosterone was 711 ng/dl. Magnetic resonance imaging showed slightly enlarged ovaries with a cyst in the left. A bilateral oophorectomy was performed, demonstrating the presence of a Leydig cell hilar tumor in the right ovary. The patient had a good postoperative evolution with reduction of androgen levels and reversion of alopecia.

  19. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2014-08-01

    appreciably over the last 3 decades. Most patients are initially responsive to treatment , however the majority develop tumor recurrence and succumb to...internalization (leftward peak shift in Par cells). Similar results were observed by immunocytochemistry (Fig 6B): TNFα treatment at 37ºC causes TNFR1... treatment at 37°C, full-length, surface TNFR1 (upper band, see inset, Fig 7) is lost in Par and EV, but not ST6-OE, cells. A similar decrease in

  20. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.

    PubMed

    Faber, Mette T; Kjær, Susanne K; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Doherty, Jennifer A; Lurie, Galina; Thompson, Pamela J; Carney, Michael E; Goodman, Marc T; Ness, Roberta B; Modugno, Francesmary; Edwards, Robert P; Bunker, Clareann H; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Larson, Melissa C; Schildkraut, Joellen; Cramer, Daniel W; Terry, Kathryn L; Vitonis, Allison F; Bandera, Elisa V; Olson, Sara H; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A; Massuger, Leon F A G; van Altena, Anne M; Vermeulen, Sita H; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P; Moysich, Kirsten B; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Risch, Harvey A; Jensen, Allan

    2013-05-01

    The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03-1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39-2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12-1.50). For these histological types, consistent dose-response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

  1. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

    PubMed Central

    Faber, Mette T.; Kjær, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Doherty, Jennifer A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Ness, Roberta B.; Modugnos, Francesmary; Edwards, Robert P.; Bunker, Clareann H.; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Larson, Melissa C.; Schildkraut, Joellen; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Bandera, Elisa V.; Olson, Sara H.; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H.; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P.; Moysich, Kirsten B.; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H.; Pike, Malcolm C.; Risch, Harvey A.

    2013-01-01

    Purpose The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. Methods We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Results Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose– response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Conclusions Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease. PMID:23456270

  2. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.

    PubMed

    McAuliffe, Shannon M; Morgan, Stefanie L; Wyant, Gregory A; Tran, Lieu T; Muto, Katherine W; Chen, Yu Sarah; Chin, Kenneth T; Partridge, Justin C; Poole, Barish B; Cheng, Kuang-Hung; Daggett, John; Cullen, Kristen; Kantoff, Emily; Hasselbatt, Kathleen; Berkowitz, Julia; Muto, Michael G; Berkowitz, Ross S; Aster, Jon C; Matulonis, Ursula A; Dinulescu, Daniela M

    2012-10-23

    Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

  3. Immunohistochemical staining of tumor necrosis factor-α and interleukin-10 in benign and malignant ovarian neoplasms.

    PubMed

    Jammal, Millena Prata; DA Silva, Allison Araújo; Filho, Agrimaldo Martins; DE Castro Côbo, Eliângela; Adad, Sheila Jorge; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2015-02-01

    Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher's exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy.

  4. Immunohistochemical staining of tumor necrosis factor-α and interleukin-10 in benign and malignant ovarian neoplasms

    PubMed Central

    JAMMAL, MILLENA PRATA; DA SILVA, ALLISON ARAÚJO; FILHO, AGRIMALDO MARTINS; DE CASTRO CÔBO, ELIÂNGELA; ADAD, SHEILA JORGE; MURTA, EDDIE FERNANDO CANDIDO; NOMELINI, ROSEKEILA SIMÕES

    2015-01-01

    Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher’s exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy. PMID:25624918

  5. Reproductive risk factors for epithelial ovarian cancer according to histologic type and invasiveness.

    PubMed

    Modugno, F; Ness, R B; Wheeler, J E

    2001-11-01

    Differences in histology among the subtypes of epithelial ovarian tumors suggest possible differences in their etiologies. We examined reproductive risk factors for epithelial ovarian cancer according to histologic subtype and tumor invasiveness. We conducted a population-based, case-control study of associations between reproductive risk factors and epithelial ovarian cancer in the Delaware Valley from 1994 to 1998. Cases age 20 to 69 years with a recent diagnosis of epithelial ovarian cancer (n = 767) were compared to community controls (n = 1367) frequency matched by age. With few exceptions, we found significant risk reduction for each histologic subtype of epithelial ovarian cancer by using oral contraceptive, bearing children, and having a tubal ligation; for each subtype, there was significant increased risk associated with a family history of the disease. There were no significant differences among histologic subtypes in the magnitude of the odds ratios for OC use, parity, breastfeeding, tubal ligation, hysterectomy, family history of breast or ovarian cancer, use of noncontraceptive estrogens, age at menarche, and age at menopause. There were also few differences between invasive and borderline tumors, except that women with borderline tumors were significantly younger than women with invasive disease (44.7 years vs. 52.0 years, p < 0.001). Among serous tumors only, women with borderline tumors were more likely to use oral contraceptives than women with invasive tumors (OR = 2.28 95% CI 1.20-4.35). The results of this study suggest that reproductive risk factors do not differ among histologic subtypes of epithelial ovarian cancers.

  6. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  7. Ovarian masses in children and adolescents in China: analysis of 203 cases.

    PubMed

    Liu, Hongqian; Wang, Xiangao; Lu, Donghao; Liu, Zhihong; Shi, Gang

    2013-01-01

    The true incidence of ovarian tumors in children is unknown. Few studies beyond case reports and case series have been published concerning pediatric ovarian tumors. Herein we review a large number of ovarian tumor cases. The charts of 203 patients who presented with adnexal masses were reviewed. The patient's ranged in age from 2 to 18 years (mean = 15.6 years), with 30 being premenarchal (14.8%). The incidence of ovarian tumor increases with age, especially in patients older than 14 years. The main complaint was abdominal pain or abdominal distension in 117 patients (57.7%). A high AFP level in a pre-pubic girl with an adnexal mass is indicative of a malignant ovarian tumor. The 214 adnexal masses (11 patients had bilateral cysts) consisted of benign tumorous oophoropathy (107 masses, 50.0%), borderline and malignant tumors (29 masses, 13.6%), and nontumorous oophoropathy (78 masses, 36.5%). Of the 136 neoplasia, germ cell tumors accounted for 71.5%. Surgical intervention was performed in 98.5% of cases. There were statistically decreased blood loss, surgery duration and days of hospitalization with the laparoscopic procedure when compared with open surgery. Abdominal pain is the most common complaint in young patients with adnexal masses. AFP is the most useful diagnostic biomarker of ovarian tumors in young females. Laparoscopic resection of ovarian cysts is an alternative operation approach.

  8. Inhibition of Notch Signaling in Combination with Paclitaxel Reduces Platinum-Resistant Ovarian Tumor Growth

    PubMed Central

    Groeneweg, Jolijn W.; DiGloria, Celeste M.; Yuan, Jing; Richardson, William S.; Growdon, Whitfield B.; Sathyanarayanan, Sriram; Foster, Rosemary; Rueda, Bo R.

    2014-01-01

    Introduction: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a γ-secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single agent therapy and in combination with standard chemotherapy. Methods: Immunocompromised mice bearing xenografts derived from clinically platinum-sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and P/C. Mice bearing platinum-resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups. Results: Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum-sensitive ovarian tumors (p < 0.05), as well as in one of three platinum-sensitive tumors (p = 0.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p < 0.05). The addition of GSI did not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting. Conclusion: Inhibiting the Notch signaling cascade with a GSI reduces primary human xenograft growth in vivo. GSI synergized with conventional cytotoxic chemotherapy only in the platinum-resistant OvCa models with single agent paclitaxel. These findings suggest inhibition of the Notch pathway in concert with taxane therapy may hold promise for treatment of platinum-resistant Ov

  9. A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth.

    PubMed

    Lal-Nag, Madhu; McGee, Lauren; Guha, Rajarshi; Lengyel, Ernst; Kenny, Hilary A; Ferrer, Marc

    2017-01-01

    The tumor microenvironment plays an important role in the processes of tumor growth, metastasis, and drug resistance. We have used a multilayered 3D primary cell culture model that reproduces the human ovarian cancer metastatic microenvironment to study the effect of the microenvironment on the pharmacological responses of different classes of drugs on cancer cell proliferation. A collection of oncology drugs was screened to identify compounds that inhibited the proliferation of ovarian cancer cells growing as monolayers or forming spheroids, on plastic and on a 3D microenvironment culture model of the omentum metastatic site, and also cells already in preformed spheroids. Target-based analysis of the pharmacological responses revealed that several classes of targets were more efficacious in cancer cells growing in the absence of the metastatic microenvironment, and other target classes were less efficacious in cancer cells in preformed spheres compared to forming spheroid cultures. These findings show that both the cellular context of the tumor microenvironment and cell adhesion mode have an essential role in cancer cell drug resistance. Therefore, it is important to perform screens for new drugs using model systems that more faithfully recapitulate the tissue composition at the site of tumor growth and metastasis.

  10. Use of chromatofocusing to distinguish estradiol receptor from ovarian-dependent and -independent rat mammary tumors.

    PubMed

    Coufalik, A H; Feldman, M; Platica, M; Toth, L; Dreiling, D; Hollander, V P

    1983-11-01

    Cytosol estradiol receptor from MTW9-D (ovarian dependent) and MTW9-MtT (ovarian independent) rat mammary tumors were fractionated by chromatofocusing, a procedure which separates proteins on an ion-exchange column as a function of isoelectric point. Receptor from MTW9-D usually fractionated as three peaks with mean pH at peak height of 7.5, 6.8, and 6.0. The intermediate peak at pH 6.8 was present in 90% of MTW9-D tumors examined but in only 20% of MTW9-MtT tumors. Treatment of cytosols with 20 mM sodium molybdate or 50 mM leupeptin did not change the chromatofocusing profiles. The pI 6.8 fraction of receptor bound quantitatively to DNA-cellulose after ammonium sulfate precipitation, while receptor in the other two peaks bound much less. The quantitative binding of a fraction of estradiol receptor characteristic of MTW9-D to DNA is consistent with the greater binding of unfractionated cytosol receptor from MTW9-D to DNA than the binding of receptor from MTW9-MtT. Sucrose gradient analysis of the pI 6.8 receptor showed a sedimentation coefficient slightly less than ovalbumin with a Stokes radius of 26 A as determined by agarose chromatography. The correlation of receptor binding to DNA with response to ovariectomy might make this form of receptor a potential marker of hormonal responsivity in mammary tumors.

  11. Molecular Profiling Reveals a Clonal Relationship Between Ovarian Mucinous Tumors and Corresponding Mural Carcinomatous Nodules.

    PubMed

    Mesbah Ardakani, Nima; Giardina, Tindaro; Amanuel, Benhur; Stewart, Colin J

    2017-09-01

    Benign or malignant mural nodules rarely occur in mucinous tumors (MTs) of the ovary and malignant nodules can show mesenchymal or epithelial differentiation. The histogenesis of mural nodules is unclear and it has been suggested that these may evolve through divergent differentiation of the mucinous neoplasm or alternatively represent a collision phenomenon. To test these possibilities we compared the molecular profile of 7 ovarian MTs with their matched mural carcinomatous nodules (MCNs) by next-generation sequencing. We found identical KRAS mutations in paired MTs and MCNs in 6 cases, one of which also showed identical CDH1 mutations in both components. In 1 tumor a KRAS mutation was detected in the mucinous neoplasm but not in the MCN; however, identical p53 mutations were present in both tumor elements. Unpaired p53 and PTEN mutations were detected only in the MCN in 2 cases, while mutations in p53 and PIK3CA genes were observed only in the MT in 2 cases. The overall comparative genomic profile was consistent with the neoplastic nature of the MCNs and strongly supported their clonal relationship with the more differentiated mucinous neoplasms. MCNs possibly develop through the acquisition of additional genomic alterations, such as p53 and PTEN mutations, resulting in an anaplastic morphologic phenotype. Our findings also suggest that ovarian MTs with MCNs often arise in KRAS mutant neoplasms. However, mutations in other genes such as PIK3CA and CDH1 may play a role in the neoplastic evolution of a subset of these tumors.

  12. [Case of ischemic heart disease resulting from persistent diuresis after giant ovarian tumor resection].

    PubMed

    Sata, Naho; Satoh, Masaaki; Seo, Norimasa

    2010-02-01

    A patient with a giant ovarian tumor weighing about 7 kg was successfully removed by operation. However, her ECG demonstrated ischemic changes after the operation. We report a case of ischemic heart disease due to persistent diuresis after giant ovarian tumor resection. A 75-year-old, 56.5 kg, 143.5 cm woman was admitted to our hospital for ovarian tumor resection. The preoperative ECG showed normal sinus rhythm and no ischemic changes. Both general anesthesia and epidural anesthesia were planed. An epidural catheter was inserted at T12-L1. Anesthesia was induced with propofol 100 mg, fentanyl 100 microg and vecuronium 8 mg under 100% oxygen inhalation. General anesthesia was maintained with sevoflurane while epidural anesthesia was achieved using 0.375% ropivacaine 6 ml. During the operation, blood pressure was 90-110/70-80 mmHg, with SaO2, 100% and heart rate, 70-80 beats x min(-1). The content of tumor was suctioned for 30 minutes. Surgery was successfully finished without any other incidence. After extubation, her ECG changed to atrial fibrillation from normal sinus rhythm and showed ST-T depression. And then her systolic blood pressure became 80 mmHg or below, but we found continued diuresis at about 10 ml x kg(-1) x hr(-1) for over 2 hr. The total of 7 unit vasopressin was intermittently given for vasoconstriction and antidiuresis. Her hemodynamic was immediately restored, and ECG turned to normal ST-T. The patient had uneventful postoperative recovery.

  13. In vivo tumor growth of high-grade serous ovarian cancer cell lines

    PubMed Central

    Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E; Cowden Dahl, Karen D.; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.

    2015-01-01

    Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community. PMID:26050922

  14. Large moderately-differentiated ovarian Sertoli-Leydig cell tumor in a 13-year-old female: A case report

    PubMed Central

    ZHANG, HUI; HAO, JING; LI, CHUN-YAN; LI, TAO; MU, YU-LAN

    2016-01-01

    Sertoli-Leydig cell tumor of the ovary, also known as androblastoma, is a rare neoplasm from the group of sex cord-stromal tumors of the ovary. The tumor accounts for <0.5% of all primary ovarian neoplasms. The clinical signs and symptoms of Sertoli-Leydig cell tumors can be associated with either hormonal production or the presence of a mass-occupying lesion. In the current study, a 13-year-old female was diagnosed with a stage Ic ovarian Sertoli-Leydig cell tumor following abdominal pain and distension. One month after a right oophorectomy, the follow-up magnetic resonance imaging scan was negative for residual or recurrent tumor. The overall 5-year survival rate for moderately-differentiated (grade 2) and poorly-differentiated (grade 3) Sertoli-Leydig cell tumors is 80%, and long-term follow-up is therefore highly advised in this patient. PMID:26893701

  15. Rare case of an ovarian vein tumor thrombosis identified on fluorodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Chandra, Piyush; Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2016-01-01

    Fludeoxyglucose positron emission tomography/computed tomography is valuable in the identification of tumor thrombus and differentiating it from bland thrombus which has implications in initiating anticoagulation. We present a rare case of tumor thrombosis in ovarian vein, in a recurrent case of uterine carcinosarcoma. PMID:27833321

  16. DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer.

    PubMed

    Piotrowska, Hanna; Myszkowski, Krzysztof; Abraszek, Joanna; Kwiatkowska-Borowczyk, Eliza; Amarowicz, Ryszard; Murias, Marek; Wierzchowski, Marcin; Jodynis-Liebert, Jadwiga

    2014-05-01

    DMU-212 has been shown to evoke a mitochondrial apoptotic pathway in transformed fibroblasts and breast cancer. However, recently published data indicated the ability of DMU-212 to evoke apoptosis in both mitochondria- and receptor-mediated manner in two ovarian cancer cell lines, namely A-2780 and SKOV-3, which showed varied sensitivity to the compound tested. The pronounced cytotoxic effects of DMU-212 observed in A-2780 cells were related to the execution of extracellular apoptosis pathway and cell cycle arrest in G2/M phase. In view of the great anticancer potential of DMU-212 against A-2780 cell line, the aim of the current study was to assess antiproliferative activity of DMU-212 in xenograft model of ovarian cancer. To evaluate in vitro metabolic properties of cells that were to be injected into SCID mice, uptake and decline of DMU-212 in A-2780 ovarian cancer cell line was investigated. It was found that the concentration of the test compound in A-2780 cells was growing within first eight hours, and then the gradual decline was observed. A-2780 cells stably transfected with pcDNA3.1/Zeo(-)-Luc vector were subcutaneously inoculated into the right flanks of SCID mice. After seven days of the treatment with DMU-212 (50mg/kg b.w), tumor growth appeared to be suppressed in the animals treated with the compound tested. At day 14 of the experiment, tumor burden in mice treated with DMU-212 was significantly lower, as compared to untreated controls. Our findings suggest that DMU-212 might be considered as a potential anticancer agent used in ovarian cancer therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

    PubMed Central

    2014-01-01

    AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-β1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-β1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-β1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-β1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-β1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-β1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-β1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-β1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer. PMID:24602453

  18. Induction of ovarian granulosa cell tumors in SWXJ-9 mice with dehydroepiandrosterone.

    PubMed

    Beamer, W G; Shultz, K L; Tennent, B J

    1988-05-15

    Spontaneous ovarian granulosa cell (GC) tumors develop in SWXJ-9 inbred mice at approximately the time of puberty. The effect of dehydroepiandrosterone (DHEA), a steroid secreted by the adrenals and reported to have antitumor actions, was examined in this ovarian tumor model. In contrast with expectations, administration of diet supplemented with 0.4% DHEA or Silastic capsules containing 10 mg DHEA resulted in a significant multifold increase in GC tumor incidence. Similar studies with metabolites of DHEA, i.e., testosterone (TESTO), dihydrotestosterone (DHT), and 17 beta-estradiol (E2), revealed that TESTO was as effective as DHEA in increasing GC tumor incidence. DHT was without effect, and E2 suppressed GC tumor incidence. Serum steroid levels and steroid target tissue responses were assessed to determine if a correlation between a change in level or response to specific steroids and GC tumorigenesis existed. In both tumor-free and GC tumor host mice, dietary or capsular treatment with DHEA, TESTO, or DHT resulted in substantial alteration in one or more of serum steroids, DHEA, androstenedione, TESTO, and DHT, in addition to the administered steroid. No consistent correlation was observed between changes in a single steroid or pattern of steroids and GC tumorigenesis. Although significant increases in serum estrogens could be detected in GC tumor hosts treated with DHEA but not TESTO, estrogens did not induce these tumors. Treatment with E2 increased only serum E2 levels. In tumor-free mice, DHEA and E2 treatments were associated with vaginal cytological evidence of estrogen action, whereas the androgens induced a leukocytic pattern. Eighty-eight % of GC tumor host mice, regardless of steroid treatment, showed a vaginal cytology pattern that included cornified cells. The evidence presented in this report leads us to hypothesize that (a) spontaneous and steroid-induced GC tumorigenesis in these mice have the same mechanism, and (b) subtle increases in DHEA or a

  19. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  20. IMP3 expression in serous tumors of the ovary.

    PubMed

    Chisté, Marcela; Alexis, John; Recine, Monica

    2014-10-01

    Insulin-like growth factor II mRNA-binding protein (IMP3) is an oncofetal protein involved in embryogenesis, which is expressed in a variety of malignant neoplasms. It is rarely expressed in normal adult tissue and benign tumors. The aim of this study was to evaluate the expression of IMP3 in benign and malignant serous tumors of the ovary. Seventy-nine ovarian tumors were examined for IMP3 expression by immunohistochemical analysis, comprising 16 benign serous tumors, 19 borderline serous tumors, and 44 serous carcinomas. Positive staining was defined as brown staining in the cytoplasm. Negative staining was defined as absent staining or staining of <5% of tumor cells. The intensity of staining (weak, moderate, and strong) and percentage (0% to 100%) of neoplastic cells staining positive for cytoplasmic IMP3 staining were recorded in each case. Moderate to strong cytoplasmic staining for IMP3 was observed in 30 of 44 (68%) serous carcinomas of the ovary; in contrast, <5% of the borderline and benign serous tumors expressed IMP3 ranging from weak to strong cytoplasmic staining. Statistically, the difference in IMP3 expression between these groups of tumors was highly significant (P<0.0001). Our findings demonstrate moderate to strong expression of IMP3 in the majority of ovarian serous carcinomas as compared with benign/borderline serous tumors, which demonstrated weak to strong expression in a small minority (<5%) of the tumors. Thus, IMP3 may be a useful adjunctive tool in the pathologic evaluation of ovarian serous tumors.

  1. [Expression Level of Membrane-associated Proteins Numb in Epithelial Ovarian Carcinoma and Its Relationship with Ovarian Cancer Stem Cell Markers CD117, CD133, ALDH1.

    PubMed

    Jing, Hong; Liu, Xiao-Yu; Chen, Ya-Li; Bai, Li-Ping; Zheng, Ai

    2016-11-01

    To explore the expression level of membrane-associated protein Numb in epithelial ovarian carcinoma and its relationship with ovarian cancer stem cell markers CD117,CD133,acetaldehyde dehydrogenase 1(ALDH1). A total of 136 patients who had ovarian tumors and 22 patients who had not ovarian tumors in Department of Gynaecology and Obstetrics,West China Second University Hospital,Sichuan University were chosen as the study subjects.According to the histopathologic examination results,they were divided into epithelial ovarian carcinoma group (n=92),ovarian borderline tumor group (n=23),ovarian benign tumor group (n=21) and normal ovary group (n=22).Expression levels of Numb protein,CD117,CD133 and ALDH1 in ovarian tissue were detected by immunohistochemical SP method and these several kinds of protein expression differences and correlation statistical analysis were performend. 1 The positive expression rate of Numb protein in epithelial ovarian carcinoma group was higher than that in benign tumor or normal ovary group,also Numb protein positive expression rate in ovarian borderline tumor group was higher than that in normal ovary group,and the differences were statistically significant (P<0.05).2 Numb protein positive expression rate in ovarian tissue in patients with epithelial ovarian carcinoma FIGO stage1-2 was lower than that in stage 3-4,also the same in no lymph nodes metastasis compared with lymph nodes invasion,and the differences of positive expression rate were statistically significant (P<0.05).While there were no significant differences among different age,histopathological types,pathological grades and residual tumor size (P>0.05).3 There was no correlation between Numb protein and CD117 and CD133 positive expression rate in epithelial ovarian carcinoma tissue [correlation coefficient (r)=0.116,P=0.261; r=0.083,P=0.425].However,the positive expression rate of Numb protein and ALDH1 was positively correlated (r=0.296,P=0.261). The expression of Numb protein

  2. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

    PubMed Central

    Duckworth, C; Zhang, L; Carroll, S L; Ethier, S P; Cheung, H W

    2016-01-01

    We previously found that the scaffold adapter GRB2-associated binding protein 2 (GAB2) is amplified and overexpressed in a subset of primary high-grade serous ovarian cancers and cell lines. Ovarian cancer cells overexpressing GAB2 are dependent on GAB2 for activation of the phosphatidylinositol 3-kinase (PI3K) pathway and are sensitive to PI3K inhibition. In this study, we show an important role of GAB2 overexpression in promoting tumor angiogenesis by upregulating expression of multiple chemokines. Specifically, we found that suppression of GAB2 by inducible small hairpin RNA in ovarian cancer cells inhibited tumor cell proliferation, angiogenesis and peritoneal tumor growth in immunodeficient mice. Overexpression of GAB2 upregulated the secretion of several chemokines from ovarian cancer cells, including CXCL1, CXCL2 and CXCL8. The secreted chemokines not only signal through endothelial CXCR2 receptor in a paracrine manner to promote endothelial tube formation, but also act as autocrine growth factors for GAB2-induced transformation of fallopian tube secretory epithelial cells and clonogenic growth of ovarian cancer cells overexpressing GAB2. Pharmacological inhibition of inhibitor of nuclear factor kappa-B kinase subunit β (IKKβ), but not PI3K, mechanistic target of rapamycin (mTOR) or mitogen-activated protein kinase (MEK), could effectively suppress GAB2-induced chemokine expression. Inhibition of IKKβ augmented the efficacy of PI3K/mTOR inhibition in suppressing clonogenic growth of ovarian cancer cells with GAB2 overexpression. Taken together, these findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. PMID:26657155

  3. Ovarian cellular fibromas lack FOXL2 mutations: a useful diagnostic adjunct in the distinction from diffuse adult granulosa cell tumor.

    PubMed

    McCluggage, W Glenn; Singh, Naveena; Kommoss, Stefan; Huntsman, David G; Gilks, C Blake

    2013-09-01

    Ovarian cellular fibromas are uncommon neoplasms, which may result in considerable diagnostic confusion with diffuse adult granulosa cell tumor. This is an important distinction, as the former usually exhibits benign behavior, whereas the latter is a low-grade malignant neoplasm capable of recurrence and metastasis. FOXL2 mutation (402C→G) has been demonstrated in >95% of ovarian adult granulosa cell tumors, only rarely in other ovarian sex cord-stromal neoplasms, and never in ovarian fibromas. In this study, we evaluated a series of ovarian cellular fibromas or mitotically active cellular fibromas (n=22), 3 with minor sex cord elements, for FOXL2 mutation. These were mostly received in consultation, often with a differential diagnosis of diffuse adult granulosa cell tumor. Immunohistochemically, 10 of 10 cases tested exhibited nuclear staining with FOXL2. FOXL2 (402C→G) mutation was not demonstrated in any of the 22 cellular or mitotically active cellular fibromas. Three additional neoplasms composed of cellular nodules of epithelioid cells in a background fibrous stroma, raising the possibility of adult granulosa cell tumor with a prominent fibrothecomatous component, were also tested; 2 of these were mutation negative, and 1 contained a FOXL2 mutation. FOXL2 mutation analysis is a useful adjunct in distinguishing between diffuse adult granulosa cell tumor (mutation present) and cellular fibroma (mutation absent). Mutation testing should be considered in problematic cases, as this will provide prognostic information for the patient.

  4. Virilizing Ovarian Stromal Tumor in a Young Woman With Carney Complex

    PubMed Central

    Carney, J. Aidan; Stratakis, Constantine A.

    2011-01-01

    A woman with Carney complex presented at age 22 years with abdominal pain and hirsutism. As a baby, she had excision of a right eyelid lesion and at age 14 years removal of a left lower eyelid nodule that subsequently recurred. Investigation revealed an elevated level of serum testosterone and a 2-cm left ovarian tumor. A left salpingo-oophorectomy was performed. Postoperatively, the abdominal pain was relieved, the serum level of testosterone was normalized, and the hirsutism was ameliorated. The tumor featured sheets of eosinophilic cells with lipochrome pigment, myeloid metaplasia, stromal metaplasia, and markedly abnormal blood vessels. Immunocytochemically, the tumor cells were positive for vimentin, synaptophysin, inhibin A and calrenin. Because of the clinical setting in which the neoplasm occurred, it is unlikely that the occurrence was unrelated to Carney complex.. PMID:21934476

  5. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-01-01

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539

  6. Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer.

    PubMed

    Khan, Anm Nazmul H; Kolomeyevskaya, Nonna; Singel, Kelly L; Grimm, Melissa J; Moysich, Kirsten B; Daudi, Sayeema; Grzankowski, Kassondra S; Lele, Sashikant; Ylagan, Lourdes; Webster, Gill A; Abrams, Scott I; Odunsi, Kunle; Segal, Brahm H

    2015-05-10

    Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages, and is associated with a high relapse rate. Patients in remission are ideal candidates for immunotherapy aimed at cure or prolonging disease-free periods. However, immunosuppressive pathways in the tumor microenvironment are obstacles to durable anti-tumor immunity. In a metastatic syngeneic mouse model of EOC, immunosuppressive macrophages and myeloid-derived suppressor cells (MDSCs) accumulate in the local tumor environment. In addition, resident peritoneal macrophages from non-tumor-bearing mice were highly immunosuppressive, abrogating stimulated T cell proliferation in a cell contact-dependent manner. Immunization with microparticles containing TLR9 and NOD-2 ligands (MIS416) significantly prolonged survival in tumor-bearing mice. The strategy of MIS416 immunization followed by anti-CD11b administration further delayed tumor progression, thereby establishing the proof of principle that myeloid depletion can enhance vaccine efficacy. In patients with advanced EOC, ascites analysis showed substantial heterogeneity in the relative proportions of myeloid subsets and their immunosuppressive properties. Together, these findings point to immunosuppressive myeloid cells in the EOC microenvironment as targets to enhance vaccination. Further studies of myeloid cell accumulation and functional phenotypes in the EOC microenvironment may identify patients who are likely to benefit from vaccination combined with approaches that deplete tumor-associated myeloid cells.

  7. Ovarian low and high grade serous carcinomas: hidden divergent features in the tumor microenvironment

    PubMed Central

    Buttarelli, Marianna; Martinelli, Enrica; Mascilini, Floriana; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Gallo, Daniela

    2016-01-01

    Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies. PMID:27462782

  8. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    PubMed Central

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff; Pedersen, Magnus; Hansen, Morten; Svane, Inge Marie

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient’s individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations expressed by the patients’ tumors and that the presence of these “neo-antigen” specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the major advances in the characterization and application of TIL therapy for patients with RCC and OC. PMID:26308285

  9. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    PubMed

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  10. A subserosal, pedunculated, multilocular uterine leiomyoma with ovarian tumor-like morphology and histological architecture of adenomatoid tumors: a case report and review of the literature.

    PubMed

    Yorita, Kenji; Tanaka, Yu; Hirano, Koki; Kai, Yuka; Arii, Kaoru; Nakatani, Kimiko; Ito, Satoshi; Imai, Toshiya; Fukunaga, Masaharu; Kuroda, Naoto

    2016-12-20

    Uterine leiomyomas are common uterine tumors, and typical cases of leiomyoma are easily diagnosed by imaging study. However, uterine leiomyomas are often altered by degenerative changes, which can cause difficulty and confusion in their clinical diagnosis. We describe the 17th reported case of a uterine leiomyoma clinically diagnosed as an ovarian tumor; however, the present case shows the most detailed radiological evaluation, including contrast-enhanced magnetic resonance imaging. We first show that a uterine leiomyoma can histologically mimic an adenomatoid tumor. A 47-year-old premenopausal, nulliparous Japanese woman with a history of type 2 diabetes mellitus, hypertension, and hyperlipidemia had lower abdominal pain. Ultrasonography confirmed a 6-cm mass in the right-sided space of the pelvic cavity. Magnetic resonance imaging evaluation showed that a multilocular mass was present near the uterus, and a mucinous ovarian tumor was considered. Emergency surgery due to acute abdomen was performed under the diagnosis of pedicle torsion of the ovarian tumor. During surgery, a pedunculated uterine mass without stalk torsion was seen. The mass grossly contained serous and hemorrhagic fluids in the cavities, and pathology examination confirmed that the mass was a leiomyoma with hydropic and cystic degeneration. Anastomosing thin cord-like arrangements of the leiomyoma cells mimicked the architecture of adenomatoid tumors. The tumor cells were positive for the microphthalmia transcription factor but negative for other melanoma markers. Three days postoperatively, she was discharged without sequelae. Marked intratumoral deposition of fluids may induce the multilocular morphology of a tumor, and the cellular arrangement of the tumor cells with hydropic degeneration mimicked an adenomatoid tumor in this case. Clinicians need to be aware that a subserosal leiomyoma with cystic and hydropic degeneration can mimic an ovarian tumor, and pathologists should be aware that such

  11. An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

    PubMed

    Erdenebaatar, Chimeddulam; Yamaguchi, Munekage; Saito, Fumitaka; Motooka, Chisato; Tashiro, Hironori; Katabuchi, Hidetaka

    2016-07-01

    Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

  12. Osteosarcoma as Malignant Mural Nodule in Ovarian Mucinous Neoplasms of Intestinal Type: Report of 2 Cases.

    PubMed

    McFarland, Marie; Dina, Roberto; Fisher, Cyril; McCluggage, W Glenn

    2015-07-01

    Mural nodules, which may be benign or malignant, are well recognized in ovarian mucinous neoplasms, especially of borderline type. Malignant mural nodules most commonly comprise anaplastic carcinoma but sarcomas of various types have been reported. We report 2 cases of osteosarcoma occurring in young women (aged 18 and 34) as malignant mural nodules in a Grade 1 ovarian mucinous carcinoma of intestinal type and a borderline mucinous tumor of intestinal type. Primary osteosarcomas of the ovary have been described either arising within a teratoma or as a pure neoplasm but, to the best of our knowledge, osteosarcoma occurring as a mural nodule in an ovarian mucinous neoplasm has not been reported. In both our cases, the tumor was Stage 1 at presentation and the patients were treated with surgery without adjuvant chemotherapy. Both patients are free of disease with follow-up of 12 and 18 mo.

  13. Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer.

    PubMed

    Davis, Lauren Z; Slavich, George M; Thaker, Premal H; Goodheart, Michael J; Bender, David P; Dahmoush, Laila; Farley, Donna M; Markon, Kristian E; Penedo, Frank J; Lubaroff, David M; Cole, Steve W; Sood, Anil K; Lutgendorf, Susan K

    2015-10-01

    The impact of psychological well-being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer. A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records. Study inclusion was confirmed after histological diagnosis. Tumor NE was measured in frozen tissue samples using high-performance liquid chromatography with electrochemical detection. Confirmatory factor analysis was used to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling was used to examine associations between these factors and tumor NE. Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (ie, compared with unitary or 2-factor models) (root mean square error of approximation, 0.048; comparative fit index, 0.982; and standardized root-mean-squared residual, 0.035). Structural equation modeling analysis that included physical well-being, stage of disease, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates was found to have good model fit (root mean square error of approximation, 0.052; comparative fit index, 0.955; and standardized root-mean-squared residual, 0.036) and demonstrated that eudaimonic well-being was related to lower tumor NE (β = -.24 [P = .045]). In contrast, no effects were found for positive affect or psychological distress. Eudaimonic well-being was found to be associated with lower tumor NE, independent of positive affect and

  14. Application of X-Ray Fluorescence Analysis to Determine the Elemental Composition of Tissues from Different Ovarian Neoplasms

    NASA Astrophysics Data System (ADS)

    Motevich, I. G.; Strekal, N. D.; Papko, N. M.; Glebovich, M. I.; Shulha, A. V.; Maskevich, S. A.

    2015-03-01

    We present the results of x-ray fluorescence analysis of tissues from healthy ovaries and from ovaries with different pathologies: benign and borderline tumors, mucinous and endometrioid cancers, serous carcinomas. We determine the average copper, zinc, calcium, selenium, cadmium, lead, and mercury levels. We observed that in the benign ovarian tumors, we see a significant decrease in the cadmium, mercury, and lead levels compared with healthy tissues. In the borderline neoplasms, the copper level is reduced relative to zinc (Cu/Zn), cadmium, mercury, and lead, and also the zinc concentration is increased. In the ovarian carcinomas, we observed changes in the ratio of the chemical elements in the tumor tissues, depending on the histologic type. The results obtained can be used for differentiation, diagnosis, and adjustment of treatment for different ovarian neoplasms.

  15. Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To-Mesenchymal-Transition and Tumor Cell Migration

    PubMed Central

    Mayer, Christine; Darb-Esfahani, Silvia; Meyer, Anne-Sophie; Hübner, Katrin; Rom, Joachim; Sohn, Christof; Braicu, Ioana; Sehouli, Jalid; Hänsch, G. Maria; Gaida, Matthias M.

    2016-01-01

    Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype. PMID:27053953

  16. The effects of selenium on tumor growth in epithelial ovarian carcinoma.

    PubMed

    Park, Jin Sun; Ryu, Ji Yoon; Jeon, Hye-Kyung; Cho, Young Jae; Park, Young Ae; Choi, Jung-Joo; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2012-07-01

    Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice was started 1 week after injection of the SKOV3ip1 cells. Treatment with selenium (1.5 mg/kg, 3 times/week) and paclitaxel injection showed no addictive effect of the inhibition of tumor growth. However, combination of selenium and paclitaxel showed the slightly increased food intake compared with paclitaxel alone. Although selenium has growth-inhibiting effect in ovarian carcinoma cells in vitro, there is no additive effect on tumor growth in mice treated with combination of paclitaxel and selenium. However, food intake is slightly higher in selenium-treated mice during chemotherapy.

  17. The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer

    PubMed Central

    Qu, Jun-ying; He, Fei

    2016-01-01

    Abstract Objective To evaluate the value of individual and combined measurement of human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125) in the diagnosis of ovarian cancer. Methods A clinical case-control study was performed in which the levels of serum HE4 and CA-125 of subjects with malignant, borderline, benign ovarian tumors and healthy women were measured before surgery. An immunohistochemistry method was used to measure the expression of HE4 in different tissues. Statistical analysis was performed to determine the relationship between the level of HE4 and the pathologic type as well as the stage of the ovarian tumors. Results The level of HE4 in the serum was significantly elevated in the malignant ovarian cancer group compared with other groups. Women with benign ovarian tumors and non-neoplastic lesions, and healthy women were designated as references. When the level of HE4 in the serum was 58.66 pmol/L, the sensitivity and specificity of HE4 in diagnosing malignant ovarian tumors was 82.35% and 96.03%, respectively. The level of HE4 was negatively correlated with the differentiation extent of the tumors whereas positively correlated to the clinical staging. In the groups of malignant and borderline tumors, the levels of HE4 were higher than the other groups. The expression of HE4 was significant higher in the serous types of ovarian tumors than that of the mucous types (P<0.05). The level of HE4 in the serum and tissues were positively correlated with each other. Conclusion HE4 can be used as a novel clinical biomarker for predicting malignant ovarian tumors and its expression was closely related with the clinical pathological features of malignant ovarian tumors. PMID:28352780

  18. Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

    PubMed Central

    Gaarenstroom, Katja N.; de Kroon, Cor D.; van Poelgeest, Mariette I.E.; Vuyk, Jaap; Bosse, Tjalling; Smit, Vincent T.H.B.M; van de Velde, Cornelis J.H.; Cohen, Adam F.; Low, Philip S.; Burggraaf, Jacobus; Vahrmeijer, Alexander L.

    2016-01-01

    Introduction Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection. PMID:27014973

  19. Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer.

    PubMed

    Virant-Klun, Irma; Kenda-Suster, Natasa; Smrkolj, Spela

    2016-03-03

    In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2-4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ. In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume. In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical "chambers", were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar "chambers" found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells. We

  20. Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model.

    PubMed

    Andersson, Håkan; Elgqvist, Jörgen; Horvath, György; Hultborn, Ragnar; Jacobsson, Lars; Jensen, Holger; Karlsson, Börje; Lindegren, Sture; Palm, Stig

    2003-09-01

    The aim of the study was to establish and refine a preclinical model to alpha-immunoradiotherapy of ovarian cancer. At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival. A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the alpha-emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect. Use of the short-range, high-linear energy transfer alpha-emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.

  1. CPTAC Releases Largest-Ever Ovarian Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).  This is one of the largest public datasets covering the proteome, phosphoproteome and glycoproteome with complementary deep genomic sequencing data on the same tumor.

  2. Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

    PubMed

    Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

    2014-04-01

    Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Clinicopathological spectrum of ovarian sex cord-stromal tumors; 20 years’ retrospective study in a developing country

    PubMed Central

    2013-01-01

    Background Ovarian sex cord stromal tumors are rare neoplasms as compared to epithelial tumors. No large study has been done in Pakistan to find out the frequencies of various sex cord stromal tumors and their clinicopathological behavior in our region. The purpose of our study was to determine the various histological patterns and clinical features of ovarian sex cord stromal tumors along with follow-up in our set-up. Methods It is a retrospective observational study. The study was conducted in section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of sex cord stromal tumors of ovary during 1992 to 2012 were retrieved. The retrieved slides were reviewed and patient demographics, clinical and pathological features were noted on proforma. SPSS Statistics Version 19 was used for all analyses. Data is expressed as absolute values and percentage or as mean ± standard deviation (SD). Results A total of 480 cases of sex cord stromal tumors were retrieved. The median age was 45 years. Bilaterality was observed in 4 cases. Of the different subtypes of sex-cord stromal tumors, most common was adult granulosa cell tumor 211(43.9%). 24 Juvenile granulosa cell tumors were retrieved (5%). Other types were fibromas 98 (20.4%) fibrothecomas 47(9.8%), thecomas 26(5.4%), sertoli-leydig cell tumors 34(7%), sclerosing stromal tumors 26 (5.4%), steroid cell tumors (10) and 4 cases of sex cord tumor with annular tubules. Of various immunohistochemical stains applied, Inhibin was frequently positive in all subtypes and focal cytokeratins were also seen commonly. Follow up information was available in 305 cases and out of these only 16 (5%) developed recurrence or metastasis. Conclusions Sex cord stromal tumors are uncommon ovarian tumors in Pakistani population, with wide age range and diverse histological types having good prognosis. Immunohistochemical markers overlap with epithelial tumors so there is need to distinguish these two. PMID

  4. Laparoscopic Treatment of Mixed Malignant Ovarian Germ Cell Tumor in a 16-Year-Old Female Adolescent.

    PubMed

    Friedman, Caroline; Fenster, Tamatha

    2016-12-01

    Malignant ovarian germ cell tumors are rare entities, although they account for a large proportion of ovarian masses in young women. These tumors have traditionally been removed via laparotomy, because of their large size and solid nature. The use of laparoscopy for treatment of adnexal masses in adolescents has been heavily debated and poorly studied to date. A 16-year-old female patient presented with abdominal pain and an 11-cm adnexal mass on ultrasound. An emergent laparoscopic salpingo-oophorectomy was performed without complication. Pathology revealed a mixed malignant ovarian germ cell tumor. Laparoscopic fertility-sparing surgery offers many benefits over laparotomy, and should be considered in cases of young women with large adnexal masses, even if potential for malignancy exists. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  5. Improving efficacy of metastatic tumor segmentation to facilitate early prediction of ovarian cancer patients' response to chemotherapy

    NASA Astrophysics Data System (ADS)

    Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille C.; Moxley, Katherine M.; Moore, Kathleen; Mannel, Robert S.; Cheng, Samuel; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-02-01

    Accurate tumor segmentation is a critical step in the development of the computer-aided detection (CAD) based quantitative image analysis scheme for early stage prognostic evaluation of ovarian cancer patients. The purpose of this investigation is to assess the efficacy of several different methods to segment the metastatic tumors occurred in different organs of ovarian cancer patients. In this study, we developed a segmentation scheme consisting of eight different algorithms, which can be divided into three groups: 1) Region growth based methods; 2) Canny operator based methods; and 3) Partial differential equation (PDE) based methods. A number of 138 tumors acquired from 30 ovarian cancer patients were used to test the performance of these eight segmentation algorithms. The results demonstrate each of the tested tumors can be successfully segmented by at least one of the eight algorithms without the manual boundary correction. Furthermore, modified region growth, classical Canny detector, and fast marching, and threshold level set algorithms are suggested in the future development of the ovarian cancer related CAD schemes. This study may provide meaningful reference for developing novel quantitative image feature analysis scheme to more accurately predict the response of ovarian cancer patients to the chemotherapy at early stage.

  6. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells.

    PubMed

    Pandey, Veethika; Oyer, Jeremiah L; Igarashi, Robert Y; Gitto, Sarah B; Copik, Alicja J; Altomare, Deborah A

    2016-02-09

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients.

  7. HE4 can help discriminate women with malignant ovariantumors only if CA125 levels are elevated.

    PubMed

    Pitta, Denise da Rocha; Sarian, Luis Otávio; Campos, Elisabete Aparecida; Andrade, Liliana Lucci De Angelo; Sallum, Luis Felipe; Bragança, Joana Froes; Campos, Camila de Mello; Derchain, Sophie

    2013-01-01

    Objective: To evaluate the performance of mesothelin, CA125, HE4 and ROMA index in the detection of malignant ovarian tumors. 
Study Design: This is a cross-sectional study including 199 women with adnexal masses (67 with malignant tumors and 132 with benign tumors) and 150 healthy women (controls). We used a recursive multivariate partitioning algorithm to assess the contribution of each of the serum markers and the ROMA index to the discrimination of women with malignant tumors. Also, the areas under the ROC curves (AUC) for each of the serum markers and for the ROMA index were compared using the Venkatraman's projection-permutation test. 
Results: In the recursive model, CA125 had the best performance in discriminating women with malignant tumors. In women with normal-range CA125 levels, none of the other markers contributed to the discrimination of women with malignant tumors. In women with elevated CA125 levels, elevated HE4 levels were associated with an increased risk of harboring a malignant tumor. The AUC for mesothelin was smaller than that for all the other curves, and both the ROMA index and CA125 had better AUC than HE4. 
 Conclusion: In women with normal CA125 levels, neither mesothelin nor HE4 contributed to discriminate women with malignant ovarian tumors; however, for women with elevated CA125 levels HE4 may help discriminating those who have a malignant ovarian tumor.

  8. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells

    PubMed Central

    Pandey, Veethika; Oyer, Jeremiah L.; Igarashi, Robert Y.; Gitto, Sarah B.; Copik, Alicja J.; Altomare, Deborah A.

    2016-01-01

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients. PMID:26802025

  9. Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

    PubMed Central

    Bu, Shixia; Wang, Qian; Zhang, Qiuwan; Sun, Junyan; He, Biwei; Xiang, Charlie; Liu, Zhiwei; Lai, Dongmei

    2016-01-01

    Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer. PMID:27845405

  10. Residual ovarian tissue mimicking malignancy in a patient with mucinous carcinoid tumor of the ovary. A case report.

    PubMed

    Burke, M; Talerman, A; Carlson, J A; Bibbo, M

    1997-01-01

    Mucinous carcinoid tumor of the ovary is an uncommon lesion in reproductive-age women. If a patient status post total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) for this tumor presents with a pelvic mass, recurrence of the tumor must be considered, as must the presence of residual ovarian tissue producing physiologic cysts with mass effect, termed the "ovarian remnant syndrome." Benign ovarian follicle cysts may have cellular atypia and mimic malignancy. A female, one year status post TAH-BSO for mucinous carcinoid tumor of the ovary, presented with pelvic mass. Clinical and radiologic evidence supported the diagnosis of recurrent tumor. Aspiration biopsy material was compatible with malignancy, and immunocytochemical stains supported a neuroendocrine origin of the cells. Surgical excision and histologic examination of the mass revealed ovarian tissue with features of corpus luteum and follicular cyst. Numerous pitfalls exist when considering an unusual tumor. While the patient's history, clinical impressions and immunocytochemistry may strongly suggest malignancy, more common benign entities may mimic malignancy and should be considered in the differential diagnosis.

  11. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B As a Cause of Secondary Amenorrhea in Adolescents with Germline DICER1 Mutation

    DTIC Science & Technology

    2017-04-06

    infancy and early childhood.8 The D/CERJ-related disorders have expanded to include other ovarian sex cord-stromal tumors Guveni le granulosa cell...in children and adolescents. Cancer. 1987; 59: 12 14 3. Schultz KA, Harris AK, Schneider OT, et al. Ovarian Sex Cord-Stromal Tumor. Journal of

  12. Accuracy of intraoperative frozen section for the evaluation of ovarian neoplasms: an institutional experience.

    PubMed

    Hashmi, Atif Ali; Naz, Samreen; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hussain, Syed Danish; Mumtaz, Shazia; Khan, Mehmood

    2016-03-31

    Ovarian neoplasms are a heterogeneous group of tumors including surface epithelial, germ cell and sex cord stromal tumors with a subset having low malignant potential (borderline tumors). While the surgical management plan differs in different categories of tumors, preoperative diagnosis is seldom available. In these circumstances, the role of frozen section becomes invaluable. In the current study, we aimed to evaluate the accuracy of the frozen section of ovarian tumors in our setup. It was a retrospective study involving 141 cases of ovarian tumors undergoing surgical resection with frozen section evaluation from January 2009 to December 2014. After gross examination, one to five blocks were prepared on the frozen section depending upon the size of the specimen. After frozen section reporting, specimens were processed routinely for final paraffin section evaluation. Results of frozen and paraffin sections were categorized in benign, borderline, and malignant, and accuracy of frozen section was determined. Out of 141 cases, 107 were diagnosed as benign on final (paraffin) examination, while 6 were borderline and 28 were malignant. Out of 107 benign cases, 45 were non-neoplastic cystic lesions of the ovary including endometriotic, follicular, and corpus luteal cysts. The most common benign neoplastic tumor was mature cystic teratoma (20 cases) followed by mucinous cystadenoma (19 cases), serous cystadenoma (14 cases), sex cord stromal tumors (8 cases), and Brenner tumor (1 case). Among borderline cases, four cases were serous and two of mucinous neoplasms. The most common malignant neoplasm was serous carcinoma (11 cases) followed by mucinous carcinoma (6 cases). The overall accuracy of frozen section diagnosis is above 99 %. The sensitivity and specificity for benign tumors were found to be 100 and 97 %, respectively. The sensitivity and specificity for borderline tumors was 83 and 99 %, respectively, while for malignant tumors, it was 96 and 100

  13. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

  14. Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients.

    PubMed

    Kar, Rajarshi; Chawla, Diwesh; Gupta, Bindiya; Mehndiratta, Mohit; Wadhwa, Neelam; Agarwal, Rachna

    2017-08-16

    Ovarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol. Complete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media. Primary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages. This study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

  15. Lung metastases of a uterine tumor resembling ovarian sex-cord tumor: Report of a rare case.

    PubMed

    Kondo, Yasuto; Sakaguchi, Shinobu; Mikubo, Masashi; Naito, Masahito; Shiomi, Kazu; Ohbu, Makoto; Satoh, Yukitoshi

    2017-09-04

    Uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a rare type of uterine neoplasm. We present an extremely rare case of lung metastases from a UTROSCT focusing on the cytologic features. A 69-year-old Japanese woman was admitted to our hospital for further examination and treatment for abnormal shadows in the right lung field. She had a history of total hysterectomy for UTROSCT. Moreover, she underwent wedge resection of the right middle lobe for lung metastasis of UTROSCT in 2011. Enhanced chest computed tomography scan revealed a solid nodule 8 mm in diameter in the right upper lobe and a well-demarcated 33-mm mass or nodule in the lower lobe. Under the diagnosis of metastatic tumors from UTROSCT, she underwent wedge resection of the right upper lobe and segmentectomy of the right S8. Cytologically, the stump smear from the resected tumors revealed round to short spindle-shaped neoplastic small cells arranged in sheets with poor cohesion and no cluster formation. The nuclei were irregular in shape, and the chromatin was finely granular, uniform, and increased. Mitotic figures were not observed. Necrosis was absent in the background. Histologically, the final diagnosis was UTROSCT group II. This is an unusual case of metastatic UTROSCT to the lung in which the cytologic features are described. © 2017 Wiley Periodicals, Inc.

  16. Ovarian granulosa cell tumor: An uncommon presentation with primary amenorrhea and virilization in a pubertal girl.

    PubMed

    Kota, Sunil Kumar; Gayatri, Kotni; Pani, Jaya Prakash; Meher, Lalit Kumar; Kota, Siva Krishna; Modi, Kirtikumar D

    2012-09-01

    A 16-year-old girl presented with primary amenorrhea and excess hair growth on her body and face for the last three years, along with pain and a mass in her lower abdomen for last one year. Examination revealed hirsutism and other virilizing features, with an irregular mass in the lower abdomen corresponding to 16 weeks'gestation. Serum testosterone was 320 ng / dl and ultrasonogram of the pelvis revealed a solid mass of 5 × 4 cm in the left adnexa. Suspecting it to be a virilizing tumor of the left ovary, the patient was subjected to staging laparotomy, which revealed stage 1a ovarian involvement amenable to surgical resection alone. Histopathological examination confirmed the diagnosis of granulosa cell tumor of the ovary. Postoperatively the serum testosterone returned to 40 ng / dl and her menstrual cycle started after two months of surgery.

  17. Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer.

    PubMed

    Kim, Soochi; Kim, Boyun; Song, Yong Sang

    2016-09-01

    Malignant ascites constitute a unique tumor microenvironment providing a physical structure for the accumulation of cellular and acellular components. Ascites is initiated and maintained by physical and biological factors resulting from underlying disease and forms an ecosystem that contributes to disease progression. It has been demonstrated that the cellular contents and the molecular signatures of ascites change continuously during the course of a disease. Over the past decade, increasing attention has been given to the characterization of components of ascites and their role in the progression of ovarian cancer, the most malignant gynecologic cancer in women. This review will discuss the role of ascites in disease progression, in terms of modulating cancer cell behavior and contributing to tumor heterogeneity. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Limitations of three-dimensional power Doppler angiography in preoperative evaluation of ovarian tumors.

    PubMed

    Silvestre, Liliane; Martins, Wellington P; Candido-Dos-Reis, Francisco J

    2015-07-29

    This study describes the accuracy of three-dimensional power Doppler (3D-PD) angiography as secondary method for differential diagnosis of ovarian tumors. Seventy-five women scheduled for surgical removal of adnexal masses were assessed by transvaginal ultrasound. Ovarian tumors were classified by IOTA simple rules and two three-dimensional blocks were recorded. In a second step analyses, a 4 cm(3) spherical sample was obtained from the highest vascularized solid area of each stored block. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were calculated. The repeatability was assessed by concordance correlation coefficient (CCC) and limits of agreement (LoA), and diagnostic accuracy by area under ROC curve. IOTA simple rules classified 26 cases as benign, nine as inconclusive and 40 as malignant. There were eight false positive and no false negative. Among the masses classified as inconclusive or malignant by IOTA simple rules, the CCCs were 0.91 for VI, 0.70 for FI, and 0.86 for VFI. The areas under ROC curve were 0.82 for VI, 0.67 for FI and 0.81 for VFI. 3D-PD angiography presented considerable intraobserver variability and low accuracy for identifying false positive results of IOTA simple rules.

  19. Effects of Wolbachia Infection and ovarian tumor Mutations on Sex-lethal Germline Functioning in Drosophila

    PubMed Central

    Sun, Sha; Cline, Thomas W.

    2009-01-01

    Wolbachia is a ubiquitous intracellular endosymbiont of invertebrates. Surprisingly, infection of Drosophila melanogaster by this maternally inherited bacterium restores fertility to females carrying ovarian tumor (cystocyte overproliferation) mutant alleles of the Drosophila master sex-determination gene, Sex-lethal (Sxl). We scanned the Drosophila genome for effects of infection on transcript levels in wild-type previtellogenic ovaries that might be relevant to this suppression of female-sterile Sxl mutants by Wolbachia. Yolk protein gene transcript levels were most affected, being reduced by infection, but no genes showed significantly more than a twofold difference. The yolk gene effect likely signals a small, infection-induced delay in egg chamber maturation unrelated to suppression. In a genetic study of the Wolbachia–Sxl interaction, we established that germline Sxl controls meiotic recombination as well as cystocyte proliferation, but Wolbachia only influences the cystocyte function. In contrast, we found that mutations in ovarian tumor (otu) interfere with both Sxl germline functions. We were led to otu through characterization of a spontaneous dominant suppressor of the Wolbachia–Sxl interaction, which proved to be an otu mutation. Clearly Sxl and otu work together in the female germline. These studies of meiosis in Sxl mutant females revealed that X chromosome recombination is considerably more sensitive than autosomal recombination to reduced Sxl activity. PMID:19171941

  20. Ovarian tumor characterization and classification: a class of GyneScan™ systems.

    PubMed

    Acharya, U Rajendra; Sree, Vinitha S; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-01-01

    In this work, we have developed an adjunct Computer Aided Diagnostic (CAD) technique that uses 3D acquired ultrasound images of the ovary and data mining algorithms to accurately characterize and classify benign and malignant ovarian tumors. In this technique, we extracted image-texture based and Higher Order Spectra (HOS) based features from the images. The significant features were then selected and used to train and test the Decision Tree (DT) classifier. The proposed technique was validated using 1000 benign and 1000 malignant images, obtained from 10 patients with benign and 10 with malignant disease, respectively. On evaluating the classifier with 10-fold stratified cross validation, we observed that the DT classifier presented a high accuracy of 95.1%, sensitivity of 92.5% and specificity of 97.7%. Thus, the four significant features could adequately quantify the subtle changes and nonlinearities in the pixel intensities. The preliminary results presented in this paper indicate that the proposed technique can be reliably used as an adjunct tool for ovarian tumor classification since the system is accurate, completely automated, cost-effective, and can be easily written as a software application for use in any computer.

  1. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  2. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.

    PubMed

    Luke, Amy M; Moroney, John W; Snitchler, Andrea; Whiteway, Susan L

    2017-05-11

    Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs). We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT. Ovarian tumors should be included in the differential diagnosis for pediatric patients who present with menstrual irregularities. Early evaluation of the hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case also emphasizes the need for testing for DICER1 mutations in pediatric patients with ovarian SLCTs. Published by Elsevier Inc.

  3. Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived ovarian cancer tissue xenografts.

    PubMed

    Kortmann, Ursula; McAlpine, Jessica N; Xue, Hui; Guan, Jun; Ha, Gavin; Tully, Sophie; Shafait, Sharaz; Lau, Alan; Cranston, Aaron N; O'Connor, Mark J; Huntsman, David G; Wang, Yuzhuo; Gilks, C Blake

    2011-02-15

    Most patients with ovarian carcinomas succumb to their disease and there is a critical need for improved therapeutic approaches. Carcinomas arising in BRCA mutation carriers display defective DNA double-strand break repair that can be therapeutically exploited by inhibition of PARP-1, a key enzyme in the repair of DNA single-strand breaks, creating synthetic lethality in tumor cells. To investigate synthetic lethality in vivo, we established a BRCA2 germline-mutated xenograft model that was developed directly from human ovarian cancer tissue, treated with the PARP inhibitor olaparib (AZD2281) alone and in combination with carboplatin. We show that olaparib alone and in combination with carboplatin greatly inhibit growth in BRCA2-mutated ovarian serous carcinoma. This effect was not observed in a serous carcinoma with normal BRCA function, showing a specific antitumor effect of olaparib in mutation carriers. Immunohistochemistry (cleaved caspase-3 and Ki-67 stains) of remnant tissue after olaparib treatment revealed significantly decreased proliferation and increased apoptotic indices in these tumors compared with untreated controls. Furthermore, olaparib-treated tumors showed highly reduced PARP-1 activity that correlated with olaparib levels. We established a BRCA2-mutated human ovarian cancer xenograft model suitable for experimental drug testing. The demonstrated in vivo efficacy of olaparib extends on the preclinical rationale for further clinical trials targeting ovarian cancer patients with BRCA mutations. ©2010 AACR.

  4. High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer

    PubMed Central

    Wang, Xiangyu; Tian, Tian; Li, Xukun; Zhao, Meng; Lou, Yanhui; Qian, Jingfeng; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

    2015-01-01

    Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients. PMID:26396916

  5. High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer.

    PubMed

    Wang, Xiangyu; Tian, Tian; Li, Xukun; Zhao, Meng; Lou, Yanhui; Qian, Jingfeng; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

    2015-01-01

    Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients.

  6. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    SciTech Connect

    Woods, Dori C.; Johnson, A.L.

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  7. Clinical characteristics and outcomes of uterine tumors resembling ovarian sex-cord tumors (UTROSCT): a systematic review of literature.

    PubMed

    Blake, Erin A; Sheridan, Todd B; Wang, Karen L; Takiuchi, Tsuyoshi; Kodama, Michiko; Sawada, Kenjiro; Matsuo, Koji

    2014-10-01

    Uterine tumor resembling ovarian sex-cord tumors (UTROSCT) is an extremely rare type of uterine tumor, and its clinical characteristics are not fully understood. A systematic literature search was conducted in PubMed and MEDLINE using the keywords, "uterine tumors resembling ovarian sex cord tumors", limited to case reports. Clinico-pathological characteristics and survival data were abstracted and evaluated for the analysis. Among 43 cases reporting UTROSCT, Type I (endometrial stromal tumors with sex cord-like elements, ESTSCLE) and Type II (classic UTROSCT) were reported in 5 (11.6%) and 17 (39.5%), respectively, and nearly half of reported UTROSCT did not subcategorize the histology pattern into Type I or II (unspecified, n=21, 48.8%). Mean age was 52.2. The two most common symptoms were postmenopausal vaginal bleeding (44.2%) and abnormal menstruation (39.5%). The majority underwent total hysterectomy with adnexectomy (65.1%) followed by hysterectomy alone (18.6%) and tumor resection alone (14.0%). Mean tumor size was 6.2cm, and extra-uterine spread was seen in 7.0%. By immunohistochemistry, calretinin expression was significantly correlated with CAM5.2, inhibin, and progesterone receptor expression (all, p<0.05). In survival analysis, disease-free survival (DFS) rates for all 43 cases at 1, 2, and 5 years for all cases were 97.0%, 92.7%, and 69.7%, respectively. Among recurrent cases, median time to recur was 24 months (range 9-48). Decreased DFS was significantly associated with pelvic pain (2-year rate, 81.8% versus 94.7%, p=0.006), histology subcategory (Type I versus II, 23.8% versus 100%, p=0.006), tumor size ≥10cm (75.0% versus 100%, p=0.046), cervical/extra-uterine metastasis (46.7% versus 100%, p=0.024), and lymphovascular space involvement (50% versus 100%, p=0.002). Treatment patterns were not statistically associated with DFS (hysterectomy, p=0.28; and adnexectomy, p=0.38). When histology patterns were examined, Type II disease was associated

  8. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  9. EphB3 protein is associated with histological grade and FIGO stage in ovarian serous carcinomas.

    PubMed

    Gao, Weiwei; Zhang, Qin; Wang, Yan; Wang, Jiandong; Zhang, Shu

    2017-02-01

    Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown. In this study, a set of ovarian tissues including normal fallopian tube, serous borderline tumor, and serous carcinoma were subjected to immunohistochemistry using a specific polyclonal antibody for EphB3. The relationship between EphB3 expression and clinicopathological parameters was statistically analyzed. EphB3 was strongly expressed in all fallopian tube specimens (19/19, 100%). EphB3 was negatively or weekly expressed in 1 of 17 (5.8%) in borderline tumors and 26 of 50 (52.0%) in serous carcinomas, moderately expressed in 7 of 17 (41.2%) in borderline tumors and 14 of 50 (28%) in serous carcinomas, and strongly expressed in 9 17 (52.9%) in borderline tumors and 10 of 50 (20%) in serous carcinomas. EphB3 expression is significantly reduced in serous carcinomas compared with normal fallopian tubes and borderline tumors (p < 0.001). EphB3 expression is negatively associated with histological grade (p < 0.001, rs = -0.613) and FIGO stage (p = 0.001, rs = -0.464) of serous carcinomas. Our results show EphB3 protein lost in ovarian serous carcinoma and is associated with tumor grade and FIGO stage, which indicate EphB3 protein may play a role in carcinogenesis of ovarian serous carcinoma and may be used as a molecular marker for prognosis.

  10. Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer.

    PubMed

    Xu, Yun; Chen, Lujun; Xu, Bin; Xiong, Yuqi; Yang, Min; Rui, Xiaohui; Shi, Liangrong; Wu, Changping; Jiang, Jingting; Lu, Binfeng

    2017-01-01

    T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues. Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients' postoperative prognoses. Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues

  11. Regression of subcutaneous lymphoma following removal of an ovarian granulosatheca cell tumor in a horse.

    PubMed

    Henson, K L; Alleman, A R; Cutler, T J; Ginn, P E; Kelley, L C

    1998-05-01

    A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous nodules and infertility. Fine-needle aspiration of one of the subcutaneous nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma. Palpation per rectum and transrectal ultrasonography revealed a mass associated with the left ovary. Excision of the ovarian tumor was performed, and a histopathologic diagnosis of granulosa-theca cell tumor was made. After removal of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring veterinarian reported that the nodules had also disappeared and then recurred after administration of a synthetic progestin. To further characterize the lymphoma and investigate this possible hormonal relationship, immunophenotyping and estrogen and progesterone receptor assays were performed. The subcutaneous lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen receptor assays were negative, and results of progesterone receptor assays were positive. Clinical observations of subcutaneous lymphoma in horses indicate that the waxing and waning nature of these tumors may be associated with the estrous cycle, pregnancy, foaling, and lactation. Clinical observations and identification of progesterone receptors suggest that a relationship between serum steroid hormone concentrations, such as estrogen and progesterone, and subcutaneous lymphoma may exists.

  12. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  13. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

    EPA Science Inventory

    Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

    Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

    Abstract
    The studies review...

  14. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

    EPA Science Inventory

    Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

    Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

    Abstract
    The studies review...

  15. Differential distribution of tumor-associated macrophages and Treg/Th17 cells in the progression of malignant and benign epithelial ovarian tumors

    PubMed Central

    Zhu, Qinyi; Wu, Xiaoli; Wang, Xipeng

    2017-01-01

    Epithelial ovarian cancer (EOC) is one of the predominant causes of cancer-associated mortality in women with gynecological oncology. Tumor-associated macrophages (TAMs), regulatory T cells (Treg cells) and T helper cell 17 (Th17) cells have been hypothesized to be involved in the progression of EOC. However, the association between TAMs and T cells remains to be elucidated. The aim of the present study was to investigate the differential distribution of TAMs, Treg cells and Th17 cells in benign ovarian tumor tissues and in tissues from patients with EOC, and to examine their association with the clinical pathology of EOC. A total of 126 tissue samples from patients with EOC and 26 tissue samples from patients with benign ovarian tumors were analyzed, and it was identified that the distribution of TAMs, Treg cells, Th17 cells and the ratio of Treg/Th17 cells were higher in the patients with EOC using triple color immunofluorescence confocal microscopy. The high frequency of TAMs and ratio of Treg/Th17 cells in late tumor grades suggested that they may be significant in tumor progression. The frequency of TAMs was different between the histological types of EOC. Immunohistochemistry was used to investigate the microvessel density (MVD) in the EOC and benign ovarian tumor tissues. A higher MVD was observed in the EOC patient tissues, particularly, in the late tumor grade tissues. The present study provided clinical data demonstrating the high distribution of TAMs and T-cells in EOC, which may contribute to tumor progression through angiogenesis. The mechanisms by which TAMs are associated with Treg cells and Th17 cells requires further investigation as prognostic factors and therapeutic targets for EOC. PMID:28123537

  16. Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Yuan, Xiangliang; Xie, Guohua; Ma, Yanhui; Shen, Lisong

    2015-01-01

    Background The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer. Materials and Methods A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted. Results This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85). Conclusion Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer. PMID:26098665

  17. Expression of wilms' tumor gene and protein localization during ovarian formation and follicular development in sheep.

    PubMed

    Logan, Kathleen A; McNatty, Kenneth P; Juengel, Jennifer L

    2003-02-01

    Wilms' tumor protein (WT1) is a transcriptional repressor essential for the development of mammalian kidneys and gonads. To gain insight into possible roles of WT1 in ovarian formation and follicular function, we studied patterns of mRNA and protein localization throughout fetal gonadal development and in ovaries of 4-wk-old and adult sheep. At Day 24 after conception, strong expression of WT1 mRNA and protein was observed in the coelomic epithelial region of the mesonephros where the gonad was forming. By Day 30, expression was observed in the surface epithelium and in many mesenchymal and endothelial cells of the gonad. Epithelial cells continued to express WT1 throughout gonadal development, as did pregranulosa cells during the process of follicular formation. However, WT1 expression was not observed in germ cells. During follicular growth, granulosa cells expressed WT1 from the type 1 (primordial) to the type 4 stages, but thereafter expression was reduced in type 5 (antral) follicles, consistent with the differentiation of granulosa cells into steroid-producing cells. The possible progenitor cells for the theca interna (i.e., the cell streams in the ovarian interstitium) expressed WT1 heterogeneously. However, differentiated theca cells in antral follicles did not express WT1. Strong expression of WT1 was observed during gonadal development, which is consistent with a role for WT1 in ovarian and follicular formation in the ewe. WT1 was identified in many cells of the neonatal and adult ovaries, including granulosa cells, suggesting that this factor is important for preantral follicular growth. However, the decline in WT1 expression in antral follicles suggests that WT1 may prevent premature differentiation of somatic cells of the follicle during early follicular growth.

  18. Tracking NF-κB activity in tumor cells during ovarian cancer progression in a syngeneic mouse model

    PubMed Central

    2013-01-01

    Background Nuclear factor-kappa B (NF-kappaB) signaling is an important link between inflammation and peritoneal carcinomatosis in human ovarian cancer. Our objective was to track NF-kappaB signaling during ovarian cancer progression in a syngeneic mouse model using tumor cells stably expressing an NF-kappaB reporter. Methods ID8 mouse ovarian cancer cells stably expressing an NF-kappaB-dependent GFP/luciferase (NGL) fusion reporter transgene (ID8-NGL) were generated, and injected intra-peritoneally into C57BL/6 mice. NGL reporter activity in tumors was non-invasively monitored by bioluminescence imaging and measured in luciferase assays in harvested tumors. Ascites fluid or peritoneal lavages were analyzed for inflammatory cell and macrophage content, and for mRNA expression of M1 and M2 macrophage markers by quantitative real-time RT-PCR. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments. Results In ID8-NGL cells, responsiveness of the reporter to NF-kappaB activators and inhibitors was confirmed in vitro and in vivo. ID8-NGL tumors in C57BL/6 mice bore histopathological resemblance to human high-grade serous ovarian cancer and exhibited similar peritoneal disease spread. Tumor NF-kappaB activity, measured by the NGL reporter and by western blot of nuclear p65 expression, was markedly elevated at late stages of ovarian cancer progression. In ascites fluid, macrophages were the predominant inflammatory cell population. There were elevated levels of the M2-like pro-tumor macrophage marker, mannose-receptor, during tumor progression, and reduced levels following NF-kappaB inhibition with thymoquinone. Conclusions Our ID8-NGL reporter syngeneic model is suitable for investigating changes in tumor NF-kappaB activity during ovarian cancer progression, how NF-kappaB activity influences immune cells in the tumor microenvironment, and effects of NF-kappaB-targeted treatments in future studies. PMID:24020521

  19. Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine Dependent Arrest in the T Cell Signaling Cascade

    PubMed Central

    Kelleher, Raymond J.; Balu-Iyer, Sathy; Loyall, Jenni; Sacca, Anthony J.; Shenoy, Gautam N.; Peng, Peng; Iyer, Vandana; Fathallah, Anas M.; Berenson, Charles S.; Wallace, Paul K.; Tario, Joseph; Odunsi, Kunle; Bankert, Richard B.

    2015-01-01

    The identification of immunosuppressive factors within human tumor microenvironments, and the ability to block these factors, would be expected to enhance patients’ anti-tumor immune responses. We previously established that an unidentified factor, or factors, present in ovarian tumor ascites fluids reversibly inhibited the activation of T cells by arresting the T cell signaling cascade. Ultracentrifugation of the tumor ascites fluid has now revealed a pellet that contains small extracellular vesicles (EV) with an average diameter of 80nm. The T cell arrest was determined to be causally linked to phosphatidylserine (PS) that is present on the outer leaflet of the vesicle bilayer, as a depletion of PS expressing EV or a blockade of PS with anti-PS antibody significantly inhibits the vesicle induced signaling arrest. The inhibitory EV were also isolated from solid tumor tissues. The presence of immune suppressive vesicles in the microenvironments of ovarian tumors and our ability to block their inhibition of T cell function represent a potential therapeutic target for patients with ovarian cancer. PMID:26112921

  20. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

    PubMed Central

    Risma, K A; Clay, C M; Nett, T M; Wagner, T; Yun, J; Nilson, J H

    1995-01-01

    Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. Images Fig. 2 Fig. 3 Fig. 5 PMID:7877975

  1. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer.

    PubMed

    Barua, Animesh; Bradaric, Michael J; Bitterman, Pincas; Abramowicz, Jacques S; Sharma, Sameer; Basu, Sanjib; Lopez, Heather; Bahr, Janice M

    2013-12-01

    Ovarian cancer (OVCA) disseminates in a distinct pattern through peritoneal metastasis and little is known about the immunosuppression in the tumor microenvironment. Our goal was to determine changes in NK cell population during OVCA development and the effects of Ashwagandha (Withania somnifera, Dunal) supplementation on NK cell localization in laying hens with OVCA. Frequency of NK cells in ovarian tumors at early and late stages in 3- to 4-year-old hens (exploratory study) as well as in hens supplemented with dietary Ashwagandha root powder for 90 days (prospective study) was examined. The population of stromal NK cells but not the intratumoral NK cells increased with OVCA development and progression. Ashwagandha supplementation decreased the incidence and progression of OVCA. Both the stromal and intratumoral NK cell population increased significantly (P < 0.0001) in Ashwagandha supplementated hens. The results of this study suggest that the population of stromal and tumorinfiltrating NK cells is increased by dietary Ashwagandha supplementation. Thus, Ashwagandha may enhance antitumor function of NK cells. This study may be useful for a clinical study to determine the effects of dietary Ashwagandha on NK cell immune function in patients with ovarian cancer. © 2013 John Wiley & Sons Ltd.

  2. Monoclonal antibodies to an epithelial ovarian adenocarcinoma: distinctive reactivity with xenografts of the original tumor and a cultured cell line.