Cancer of the ovaries are the second most common group of gynaecologic cancers, and account for about 5% of all women's cancers. There are two main types; (i) epithelial tumours (carcinomas) which account for 90% of ovarian cancers, and (ii) non-epithelial tumours (eg. Stroma cell and germ cell tumours of the ovary). The epithelial ovarian cancers are usually found in women aged over 40, while the non-epithelial tumours are more common in girls and young women. Epithelial ovarian cancer has few early symptoms, a risk factor is having a family history of the disease. Taking the contraceptive pill is known to be protective against ovarian cancer.
A non-profit organization, working to increase awareness and educate Georgia’s women of all ages and their families, and the healthcare community about the risks and symptoms leading to early detection.
Roswell Park Cancer Institute The registry, founded in, is researching the causes of familial cancer. Women over the age of 18, in families with 2 or more diagnoses of ovarian cancer are eligible to register. The site includes details of research and information about ovarian cancer.
A national organisation, incorporated in 2001, which aims to support, educate, advocate, and promote research. The website includes extensive information about ovarian cancer and details of local support groups.
SCOCF Founded by patients in 1999, SCOCF provides support for ovarian cancer patients, education of the public and healthcare providers, and aims to further research on ovarian cancer in the state of South Carolina.
PubMed Central search for free-access publications about Ovarian Cancer MeSH term: Ovarian Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
This list of publications is regularly updated (Source: PubMed).
Roberts OA, Oranye BC Ovarian dysgerminoma in an adolescent: a case report. Afr J Med Med Sci. 2013; 42(2):197-200 [PubMed] Related Publications
INTRODUCTION: Ovarian cancer is the second most frequent gynaecological cancer in Nigeria ranking next after carcinoma of the cervix. It has the highest case-fatality rate worldwide because of insidious onset, lack of effective screening methods and late presentation. This case of a sixteen-year old girl with a three-week history of abdominal pain which was later accompanied by abdominal swelling is a classic example of how dysgerminomas present. METHOD: The presumptive diagnosis of an ovarian tumour was made after physical examination and this was later confirmed by ultrasound scan. Urgent laparotomy was carried out based on a suspicion of torsion of the pedicle of the cyst. RESULT: At laparotomy, torsion of the pedicle with an intact capsule and imminent gangrene were found. The histology report revealed a malignant germ cell neoplasm (Dysgerminoma) with focal areas of necrosis without infiltration of the attached omentum. CONCLUSION: She had conservative surgery (left oophorectomy) done. She, however, defaulted from further follow-up.
Hammer A, Lauszus FF, Petersen AC Ovarian granulosa cell tumor and increased risk of breast cancer. Acta Obstet Gynecol Scand. 2013; 92(12):1422-5 [PubMed] Related Publications
Granulosa cell tumor of the ovary (GCT) is a rare neoplasm. The tumor often secretes estrogens and then presents at an earlier stage due to hormone-related symptoms. GCT women are at increased risk of endometrial carcinoma, but there is only limited information about GCTs and potential association to other hormone-related neoplasms such as breast cancer. We conducted a retrospective follow-up study on 163 women with GCT. Medical records and histological sections were reviewed and a search in the pathology registry performed. Eight [95% confidence interval (CI); 3.4-15.8] GCT women were diagnosed with a breast neoplasm; one with Paget's disease of the nipple and seven with breast carcinoma. Based on calculations using incidence rates on breast cancer among Danish women, we would have expected 2.5 cases of breast cancer. The odds ratio was 3.3 (95% CI, 1.6-6.6), suggesting an increased risk of breast cancer in GCT women.
Prorocic M, Tasic L, Vasiljevic M, et al. Simultaneous dermoid cyst and endometriosis in the same ovary: a case report. Clin Exp Obstet Gynecol. 2013; 40(3):457-9 [PubMed] Related Publications
The authors present a case of a 33-year-old infertile woman with coincidental dermoid cyst and ovarian endometriosis in the same ovary. She was admitted to the Clinic because of cystic tumor of the left adnexa. Transvaginal ultrasound (TVUS) examination found a bilocular tumor of complex structure on the left ovary. Video-laparoscopy was also performed. On the left ovary, two adjacent cystic formations were found. Laparoscopic ovarian cystectomy was performed and a surgical specimen was sent for histopathologic analysis. The diagnosis was a dermoid cyst and ovarian endometriosis. Without complications, the patient was released from the hospital. The patient was treated with an analogue of gonadotropin releasing hormone (GnRH) for three months as a preparation for in vitro fertilization (IVF).
Alvarado-Cabrero I, Rodríguez-Gómez A, Castelan-Pedraza J, Valencia-Cedillo R Metastatic ovarian tumors: a clinicopathologic study of 150 cases. Anal Quant Cytol Histol. 2013; 35(5):241-8 [PubMed] Related Publications
OBJECTIVE: To determine the frequency of metastatic ovarian tumors and to identify their clinicopathologic features. STUDY DESIGN: A total of 150 patients with pathologically confirmed metastatic ovarian carcinoma who were treated between 1995 and 2011 at the Mexican Oncology Hospital were identified by retrospective review. Clinicopathologic data were analyzed. RESULTS: Metastatic ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%). Gynecologic primary sites were the uterine cervix (4%) and the uterine body (23%). Primary malignancies were detected first in 66 patients (44%) and simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass was the first manifestation of disease in 20.6% of the cases. The patients ranged in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35 patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid-cystic in 38, and multicystic in 44. CONCLUSION: Metastatic ovarian carcinomas are an important group of ovarian neoplasms, constituting 15.7% of all ovarian malignancies. Most of them arise from the gastrointestinal tract.
Collins IM, Milne RL, Weideman PC, et al. Preventing breast and ovarian cancers in high-risk BRCA1 and BRCA2 mutation carriers. Med J Aust. 2013; 199(10):680-3 [PubMed] Related Publications
OBJECTIVE: To estimate the prevalence of the use of cancer risk-reducing measures among Australian BRCA1 and BRCA2 mutation carriers. DESIGN, SETTING AND PARTICIPANTS: Prospective follow-up of female carriers of BRCA1 or BRCA2 mutations who had no personal history of cancer and were enrolled in a multiple-case breast cancer family cohort study (kConFab). Data, including cancer events and uptake of risk-reducing surgery and medication were collected by self-report at cohort entry and 3 yearly thereafter. Surgery was confirmed from pathology and medical records. Women were followed up from enrolment until cancer diagnosis, date of last follow-up, or death. Data were collected from 3 November 1997 to 21 May 2012. MAIN OUTCOME MEASURES: Uptake of risk-reducing surgery and/or medication. RESULTS: Of 175 BRCA1 and 150 BRCA2 mutation carriers (median age, 37 years at cohort enrolment), 69 (21%) underwent risk-reducing mastectomy, 125 (38%) underwent risk-reducing bilateral salpingo-oophorectomy and nine (3%) participated in a clinical trial of risk-reducing medication, during 2447 person-years of follow-up (median follow-up, 9 years). Sixty-eight women (21%) reported incident cancers, including 52 breast cancers and nine ovarian cancers (defined in this article as high-grade serous cancers of the ovary, fallopian tube or peritoneum). CONCLUSIONS: There is considerable scope to increase the uptake of cancer risk-reducing measures in Australian BRCA1 and BRCA2 mutation carriers. These findings should drive (i) future research into the factors contributing to low uptake in Australia and (ii) changes to policy and practice to help better translate genetic knowledge into reductions in cancer incidence.
Furukawa S, Soeda S, Kiko Y, et al. MCP-1 promotes invasion and adhesion of human ovarian cancer cells. Anticancer Res. 2013; 33(11):4785-90 [PubMed] Related Publications
BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) can accelerate tumor progression by attracting tumor-associated macrophages. We studied the effects of MCP-1 on SKOV-3 cells in order to investigate MCP-1 biological activity ovarian cancer. MATERIALS AND METHODS: A SKOV-3 cell invasion assay (Transwell assay) and cell adhesion assay (96-well assay) were performed. Immunohistochemical staining for C-C motif chemokine receptor-2 (CCR2), a receptor for MCP-1, was also performed on cultured SKOV-3 cells. RESULTS: Migration and adhesion of MCP-1-treated SKOV-3 cells were significantly increased compared to untreated cells (p<0.01). A CCR2 antagonist attenuated the invasion and adhesion of MCP-1-treated cells. CCR2 was expressed in the cytoplasm of SKOV-3 cells. CONCLUSION: MCP-1 promoted invasion and adhesion of ovarian cancer cells, and a CCR2 antagonist attenuated the effects of MCP-1 in vitro. These data suggest that MCP-1 is a potential therapeutic target for ovarian cancer therapy.
High-grade serous ovarian cancers (HGSCs) are characterized by a high frequency of TP53 mutations, BRCA1/2 inactivation, homologous recombination dysfunction, and widespread copy number changes. Cyclin E1 (CCNE1) gene amplification has been reported to occur independently of BRCA1/2 mutation, and it is associated with primary treatment failure and reduced patient survival. Insensitivity of CCNE1-amplified tumors to platinum cross-linking agents may be partly because of an intact BRCA1/2 pathway. Both BRCA1/2 dysfunction and CCNE1 amplification are known to promote genomic instability and tumor progression. These events may be mutually exclusive, because either change provides a path to tumor development, with no selective advantage to having both mutations. Using data from a genome-wide shRNA synthetic lethal screen, we show that BRCA1 and members of the ubiquitin pathway are selectively required in cancers that harbor CCNE1 amplification. Furthermore, we show specific sensitivity of CCNE1-amplified tumor cells to the proteasome inhibitor bortezomib. These findings provide an explanation for the observed mutual exclusivity of CCNE1 amplification and BRCA1/2 loss in HGSC and suggest a unique therapeutic approach for treatment-resistant CCNE1-amplified tumors.
Ackerman S, Irshad A, Lewis M, Anis M Ovarian cystic lesions: a current approach to diagnosis and management. Radiol Clin North Am. 2013; 51(6):1067-85 [PubMed] Related Publications
The primary imaging modality for evaluation of ovarian cystic lesions is pelvic ultrasonography. Most ovarian cysts are benign and demonstrate typical sonographic features that support benignity. However, some ovarian cystic lesions have indeterminate imaging features, and the approach to management varies. This article discusses how to recognize and diagnose different types of ovarian cystic lesions, including an approach to management. The learning objective is to recognize imaging features of ovarian cystic lesions.
Bakrin N, Bereder JM, Decullier E, et al. Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients. Eur J Surg Oncol. 2013; 39(12):1435-43 [PubMed] Related Publications
BACKGROUND: Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS: A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS: The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION: For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.
Kohorn EI Uracil mustard and 5-fluorouracil combination chemotherapy: a historic record. Conn Med. 2013; 77(7):433-6 [PubMed] Related Publications
BACKGROUND: Uracil mustard and 5-fluorouracil (UM-FU) combination chemotherapy was used as one of the earliest combination chemotherapies in ovarian carcinoma from 1964 to 1971 at Yale New Haven Medical Center. METHODS: UM-FU was offered to patients with stage III and IV, histologically verified, ovarian carcinoma. Uracyl mustard was administered orally--1 mg/ kg, daily. 5-Fluorouracyl was administered every four weeks at 5 mg/kg for five days by intravenous infusion. RESULTS: Of a total 185 patients with ovarian cancer, 76 received UM-FU. Thirty-five patients had measurable disease. Fifteen (42%) showed objective response lasting three to 95 months, with decrease in size of masses and disappearance of ascites or hydrothorax. Their survival from diagnosis to death was 41 months. Twenty patients showed no response; their mean survival was 18 months. Three of the 76 patients who received UM-FU developed acute nonlymphocytic leukemia. CONCLUSION: UM-FU was effective in controlling ascites and hydrothorax and diminished intraabdominal masses. The discovery of adriamycin and then platinum led to more effective therapy and the use of uracil mustard was superseded. It is no longer available. The experience reported is of historic interest.
Maraka S, Bulathsinghala CP, Grover P Brain on fire: anti-N-methyl-D-aspartate-receptor encephalitis associated with ovarian teratoma. Conn Med. 2013; 77(7):389-92 [PubMed] Related Publications
INTRODUCTION: Anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis is the most common antibody-defined autoimmune neuronal disorder. It may present with psychiatric symptoms, decreased consciousness, and hypoventilation. DATA SOURCES: A 33-year old female presented with agitation and psychotic symptoms following a flu-like illness. She was treated for a presumed psychiatric disorder before she developed seizures and respiratory failure. An extensive workup including routine blood work, brain imagining, electroencephalography, and cerebrospinal fluid analysis was unremarkable. After a prolonged hospital stay requiring multiple antiepileptic drugs and sedatives, a computerized tomography of the abdomen revealed an ovarian tumor. Immunosuppressive therapy was initiated and the tumor was resected, when anti-NMDAR encephalitis was suspected. The diagnosis was confirmed following a positive anti-NMDAR antibody. CONCLUSION: Anti-NMDAR encephalitis should be considered in the differential diagnosis of a diverse array of conditions. This case report emphasizes the importance of investigating such patients since proper treatment could potentially prevent neurologic complications or death.
Sun C, Li N, Yang Z, et al. miR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition. J Natl Cancer Inst. 2013; 105(22):1750-8 [PubMed] Related Publications
BACKGROUND: Expression of BRCA1 is commonly decreased in sporadic ovarian cancer, and this is associated with platinum sensitivity and favorable prognosis. However, multiple mechanisms underlying low BRCA1 expression are not fully understood. METHODS: A bioinformatics-driven microRNA (miR) library screening was used to identify miRs that regulate BRCA1 expression. The effects of miR-9 on cisplatin (cDDP) and PARP inhibitor sensitivity were measured in ovarian cancer cells and C13* xenograft mice (n = 6 per group). The roles of miR-9 on prognosis were assessed in a cohort of ovarian cancer patients (n = 113) with Kaplan-Meier and Cox proportional hazards analyses. All statistical tests were two-sided. RESULTS: Reverse miR library screening revealed that miR-9 reduced the normalized luciferase activity to 60.3% (95% confidence interval [CI] = 52.0% to 68.5%; P < .001). miR-9 bound directly to the 3'-UTR of BRCA1 and downregulated BRCA1 expression in ovarian cancer cells. Treatment with miR-9 agomiR sensitized BRCA1-proficient C13* xenograft tumors to cisplatin and AG014699. In serous ovarian cancer, higher levels of miR-9 were inversely correlated with BRCA1 expression (Spearman rank correlation: R (2) = 0.379; P = .003). Patients with higher levels of miR-9 had better chemotherapy response, platinum sensitivity, and longer progression-free survival (PFS) (high vs low miR-9 expression: median PFS = 26.4 months, 95% CI = 13.8 to 39.0 months vs median PFS = 15.4 months, 95% CI = 6.8 to 23.9 months, P = .01). CONCLUSIONS: miR-9 mediates the downregulation of BRCA1 and impedes DNA damage repair in ovarian cancer. miR-9 may improve chemotherapeutic efficacy by increasing the sensitivity of cancer cells to DNA damage and may impact ovarian cancer therapy.
Cho H, Lee YS, Kim J, et al. Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Invest. 2013; 31(9):607-15 [PubMed] Related Publications
Illumina microarray was used to identify differentially expressed genes in three epithelial ovarian cancer (EOC) cells. To validate the microarray data, mRNA and protein level of glucose transporter-1 (GLUT-1) was examined. GLUT-1 had an EOC/normal cells ratio of 5.51 based on microarray. Real-time PCR and immunohistochemistry demonstrated that GLUT-1 expression was significantly increased in EOC (p = .029 and p < .001, respectively). On survival analysis, GLUT-1 overexpression (HR = 4.80, p = .027) and lymph node metastases (HR = 8.35, p = .016) conferred a significantly worse overall survival. In conclusion, GLUT-1 expression is remarkably upregulated in EOC and predicts a poor overall survival.
David L, Dinu I, Vatachki G, et al. Surgical treatment of advanced ovarian cancer. Khirurgiia (Sofiia). 2013; (2):4-11 [PubMed] Related Publications
BACKGROUND: The classical treatment for advanced ovarian cancer (OC) consists of a optimal cytoreductive surgery (when the postoperative residual tumor is under 1 cm.), followed by adjuvant chemotherapy based on platinum or paclitaxel derivatives. The 5-year survival rate in case of advanced OC with secondary peritoneal carcinomatosis (PC) is below 25%. The treatment of PC (interpreted as a local-regional disease and not as a systemic disease) is based on an aggressive surgical act (a full or maximal cytoreduction without residual tumor), followed by local chemotherapy or hypertermic intraperitoneal chemotherapy. This is a retrospective study which reassesses the surgical treatment of advanced OC within the period January 2004 - December 2010 in the Center of General Surgery and Liver Transplantation within Fundeni Institute. METHODS: In the period January 2004 - December 2010 in the Center of General Surgery and Liver Transplantation within Fundeni Institute were operated 405 patients with advanced ovarian cancer. In 105 patients (25.9%) intraperitoneal chemotherapy with Cisplatin was performed. RESULTS: Overal survival was calculated for a subsample of 297 patients, for whom it was possible to properly ensure the follow-up, being of 43 months in the patients with intraperitoneal chemotherapy (p = 0.02) and 37 months in the patients without intraperitoneal chemotherapy. CONCLUSIONS: The maximal cytoreduction associating IPCH is an aggressive multidisciplinary therapeutic approach in advanced OC, reserved for difficult cases, considered in the past without solution. In properly selected cases, this shows a clear increase in survival rate.
The tumor microenvironment plays an important role in the progression of cancer. This study focused on carcinoma-associated fibroblasts (CAFs) and stromal-epithelial interaction between CAFs and epithelial ovarian carcinoma (EOC) cells. We isolated and established primary cultures of CAFs and co-cultured CAFs and EOC cells in vitro. The co-culture conditioned medium (CC-CM) was harvested and its influence on EOC cells was examined. Cytokine, chemokine, and growth factor levels were screened using a biotin label-based human antibody array system. We found that the stromal-epithelial crosstalk provided a suitable microenvironment for the progression of ovarian cancer cells in vitro.
Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013; 31(33):4188-98 [PubMed] Related Publications
PURPOSE: To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. METHODS: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. RESULTS: From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. CONCLUSION: Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.
Guo J, Xia B, Meng F, Lou G miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1. Biochem Biophys Res Commun. 2013; 441(2):357-63 [PubMed] Related Publications
Astrocyte elevated gene-1 (AEG-1) is an oncogene overexpressed in multiple types of human cancers including ovarian cancer (OC). However, the underlying mechanism of AEG-1 up-regulation in OC is not well understood. In this study, we showed that miR-137 downregulated AEG-1 expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 expression was inversely correlated with AEG-1 levels in OC specimens. Similar to the downregulation of AEG-1, overexpression of miR-137 in OC cell lines decreased in vitro cell growth, clonogenicity, and also induced G1 arrest. Importantly, miR-137 overexpression suppressed in vivo tumor growth in nude mice models. Furthermore, we found that restoring the AEG-1 (without the 3'UTR) significantly rescued miR-137-induced cell growth inhibition and cell-cycle arrest. Taken together, these findings indicate that miR-137 functions as a tumor suppressor by inhibition of AEG-1. These molecules might be targets for prevention or treatment of OC.
Widschwendter M, Rosenthal AN, Philpott S, et al. The sex hormone system in carriers of BRCA1/2 mutations: a case-control study. Lancet Oncol. 2013; 14(12):1226-32 [PubMed] Related Publications
BACKGROUND: Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and altered end-organ hormone sensitivity might explain this organ-specific penetrance. We sought to identify differences in hormone regulation between carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations. METHODS: We assessed endometrial thickness for each menstrual cycle day (as an index of hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754 women known to be negative for the mutations. To quantify differences in endometrial thickness we focused on days 10-14 and days 21-26, and calculated the area under the curve. We then compared serum oestradiol and progesterone titres during these days of the menstrual cycle in the same groups. Follicular and luteal oestradiol and progesterone serum titres were grouped into quartiles and odds ratios were calculated with logistic regression. FINDINGS: Follicular phase endometrial thickness of carriers of the mutations adjusted for age and day of the menstrual cycle was higher (odds ratio [OR] 1·11, 95% CI 1·03-1·20; p=0·0063) and luteal phase endometrial thickness lower (0·90, 0·83-0·98; p=0·027) than for women negative for the mutations. Median luteal phase titres of progesterone were 121% higher (p=0·00037) in carriers than in women negative for the mutations, and for oestradiol were 33% higher (p=0·007)-ie, 59% of carriers had concentrations of serum progesterone that would have been in the top quartile of concentrations in the control group (OR 8·0, 95% CI 2·1-52·57; p=0·008). INTERPRETATION: Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesterone-known risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women. Our findings could not be explained by differential contraceptive pill use.
Witkowski L, Mattina J, Schönberger S, et al. DICER1 hotspot mutations in non-epithelial gonadal tumours. Br J Cancer. 2013; 109(10):2744-50 [PubMed] Article available free on PMC after 12/11/2014 Related Publications
BACKGROUND: Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observations. METHODS: We used Sanger sequencing to sequence the RNase IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19 males, as well as 43 extra-gonadal GCTs from 26 females and 17 males. RESULTS: We identified heterozygous non-synonymous mutations in the RNase IIIb domain of DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28 SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8 miscellaneous tumours. The 14 mutations affected only five residues: E1705, D1709, E1788, D1810 and E1813. In all five patients where matched and constitutional DNA was available, the mutations were only somatic. There were no mutations found in the RNase IIIa domain. CONCLUSION: More than half (8/15) of Sertoli-Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs may aid in classification and provide new approaches to therapy.
Stewart CJ, Alexiadis M, Crook ML, Fuller PJ An immunohistochemical and molecular analysis of problematic and unclassified ovarian sex cord-stromal tumors. Hum Pathol. 2013; 44(12):2774-81 [PubMed] Related Publications
Most ovarian sex cord-stromal tumors (SCSTs) can be categorized on the basis of conventional histology, but approximately 10% of cases are unclassified because they present indeterminate or overlapping morphologic features. Immunohistochemical and molecular studies of unclassified ovarian SCST are very limited, but recently, it has been demonstrated that 2 major subgroups of SCST, adult-type granulosa cell tumor and Sertoli-Leydig cell tumor, are characterized by somatic mutations in FOXL2 and DICER1, respectively. In this study, 12 diagnostically problematic ovarian SCST, including 9 unclassified tumors, were investigated for FOXL2 and DICER1 mutations and for immunohistochemical expression of calretinin, CD56, CD99, estrogen receptor α, estrogen receptor β, FOXL2, inhibin, progesterone receptor, and steroidogenic factor-1. Four of 11 tumors with satisfactory analysis showed a FOXL2 mutation; 3 of these cases were reported initially as unclassified SCST and 1 as Sertoli-Leydig cell tumor. Conversely, 3 cases with an original diagnosis of granulosa cell tumor were FOXL2 mutation-negative, and none of 7 tumors with satisfactory analysis demonstrated a DICER1 mutation. All tumors expressed at least 4 of the immunomarkers examined, although staining was often focal and there was no consistent correlation with tumor morphology. In conclusion, molecular analysis is useful in the assessment of diagnostically challenging ovarian SCST. The absence of FOXL2 and DICER1 mutations in most unclassified SCST suggests that these could represent a distinct tumor subgroup with different molecular pathogenesis. Immunohistochemical profiles overlap with those of better categorized SCST, but staining may be focal or negative emphasizing the requirement for antibody panels in diagnostic assessment.
Sehn JK, Kuroki LM, Hopeman MM, et al. Ovarian complete hydatidiform mole: case study with molecular analysis and review of the literature. Hum Pathol. 2013; 44(12):2861-4 [PubMed] Related Publications
Ectopic complete molar pregnancy in the ovary is an exceptionally rare event. Here we present a case of ovarian complete hydatidiform mole in a 20-year-old gravida 2 para 1 woman. At presentation, the patient underwent excision of a hemorrhagic left ovarian cyst, with routine sections demonstrating a hemorrhagic corpus luteum with a single microscopic focus of detached atypical trophoblast, without chorionic villi. Subsequent left salpingo-oophorectomy for persistently elevated human chorionic gonadotropin led to a final diagnosis of complete hydatidiform mole arising in the ovary. The fallopian tube was unremarkable. Zygosity was determined using short tandem repeat analysis, confirming the diagnosis of monospermic complete mole. In the clinical setting of a markedly elevated human chorionic gonadotropin level and an ovarian mass, histopathologic examination is critical in distinguishing ectopic pregnancy from choriocarcinoma. Short tandem repeat analysis can be a useful adjunct to histologic diagnosis in challenging cases.
Robbins JR, Gayar OH, Zaki M, et al. Impact of age-adjusted Charlson comorbidity score on outcomes for patients with early-stage endometrial cancer. Gynecol Oncol. 2013; 131(3):593-7 [PubMed] Related Publications
OBJECTIVES: To determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer. METHODS: After IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I-II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0-1 (n=204), 2-3 (n=293) and >3 (n=174). Kaplan-Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint. RESULTS: After a median follow-up of 85 months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0-1; 81.7%, 95.3%, and 89.8% for AAC 2-3: and 56%, 88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not. CONCLUSIONS: Comorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma.
Arend RC, Londoño-Joshi AI, Straughn JM, Buchsbaum DJ The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013; 131(3):772-9 [PubMed] Related Publications
OBJECTIVE: Ovarian cancer is the deadliest gynecologic malignancy and the fifth leading cause of death from cancer in women in the U.S. Since overall survival remains poor, there is a need for new therapeutic paradigms. This paper will review the Wnt/β-catenin pathway as it relates to epithelial ovarian cancer, specifically its role in chemoresistance and its potential role as a target for chemosensitization. METHODS: A PubMed search was performed for articles published pertaining to Wnt/β-catenin pathway specific to ovarian cancer. Wnt/β-catenin signaling pathways play an active role in cancer stem cells (CSCs) and carcinogenesis of all ovarian cancer subtypes. Studies also have shown that ovarian CSCs are involved in chemoresistance, metastasis, and tumor recurrence. RESULTS: Wnt/β-catenin target genes regulate cell proliferation and apoptosis, thereby mediating cancer initiation and progression. The Wnt/β-catenin pathway is one of the major signaling pathways thought to be involved in epithelial-to-mesenchymal transition (EMT). Alterations affecting Wnt pathway proteins on the cell membrane, in the cytoplasm, and in the nucleus have been shown to play important roles in the tumorigenesis of ovarian cancer. CONCLUSIONS: Wnt signaling is activated in epithelial ovarian cancer. Given the role of the Wnt/β-catenin pathway in carcinogenesis, more pre-clinical studies are warranted to further investigate other Wnt inhibitors in ovarian cancer. The Wnt pathway should also be investigated as a potential target in the development of new drugs for ovarian cancer as a single agent and in combination with chemotherapy or other targeted agents.
Fadare O, Parkash V, Gwin K, et al. Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas. Hum Pathol. 2013; 44(12):2814-21 [PubMed] Article available free on PMC after 01/12/2014 Related Publications
The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes.
Xiao K, Suby N, Li Y, Lam KS Telodendrimer-based nanocarriers for the treatment of ovarian cancer. Ther Deliv. 2013; 4(10):1279-92 [PubMed] Related Publications
PEG-dendritic block copolymer (telodendrimer) is a unique class of polymers with well-defined structures and tunable aggregation properties, which have been recently developed as novel micelle-based nanocarriers. This new class of nanocarrier is highly versatile, robust, multifunctional and has many unique properties for drug delivery that are superior to most other nanocarriers reported in the literature. Reversible crosslinking of micelles is able to minimize the premature drug release during circulation. These crosslinks can be reversed with endogenous and/or exogenous stimuli. To further facilitate the precise delivery of nanoparticle drugs to cancer cells, the nanoparticles surface can be decorated with ovarian cancer targeting ligands. This review is focused on the various strategies used for the design, preparation, pharmacokinetic, biodistribution and preclinical therapeutic applications of telodendrimer-based nanocarriers for drug delivery in the treatment of ovarian cancer. Lastly, future perspectives for the development of ovarian cancer-targeting telodendrimer nanotherapeutics are also explored.
Zhu CS, Pinsky PF, Kramer BS, et al. The prostate, lung, colorectal, and ovarian cancer screening trial and its associated research resource. J Natl Cancer Inst. 2013; 105(22):1684-93 [PubMed] Related Publications
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses' Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.
Khadim MF, Eastwood P, Price J, et al. Multidisciplinary one-stage risk-reducing gynaecological and breast surgery with immediate reconstruction in BRCA-gene carrier women. Eur J Surg Oncol. 2013; 39(12):1346-50 [PubMed] Related Publications
Familial breast cancer accounts for 5-10% of all breast cancers. Due to BRCA1/2 tumour suppressor gene mutation, hereditary breast and ovarian syndrome is the most common form. Risk-reducing gynaecological and breast surgery is offered to such patients in ever-increasing numbers. Hence, the development of a multi-specialty combined treatment approach is called for. Twenty-two BRCA gene-mutation carrier women underwent one-stage gynaecological and breast risk-reducing surgery and immediate reconstruction between January 2005 and December 2011 at the Belfast City Hospital. Their mean age was 41.2 years (median 41 years). Nearly half of the patients were BRCA2 and a quarter were BRCA1 carriers. The rest were positive for both genes. Hormone-replacement therapy was initiated in 14 women. Average theatre time and stay in the hospital were three hours and two and a half days, respectively. Two patients developed complications unrelated to combining the procedures. Both were treated conservatively and recovered. The one-stage approach logically proves economical by limiting the time the patients are in the hospital and away from work. We describe our multidisciplinary team service that is offering safe and economical one-stage risk-reducing surgery and reconstruction to young BRCA gene-mutation carrier women in Northern Ireland.
Howell EA, Egorova N, Hayes MP, et al. Racial disparities in the treatment of advanced epithelial ovarian cancer. Obstet Gynecol. 2013; 122(5):1025-32 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
OBJECTIVE: To examine whether treatment with guideline-recommended care (surgery and chemotherapy) is associated with mortality differences between black and white women with advanced epithelial ovarian cancer. METHODS: We conducted an observational cohort study using the Surveillance, Epidemiology, and End Results (SEER) linked to Medicare claims for 1995-2007. We evaluated long-term survival for 4,695 black and white women with stage III or stage IV epithelial ovarian cancer with Kaplan-Meier analysis and Cox regression, and then in patients matched by propensity score to create two similar cohorts for comparison. We investigated the association between race, stage, and survival among women who were treated with guideline-recommended care and those who received incomplete treatment. RESULTS: Black women with advanced epithelial ovarian cancer were more likely to die than white women (unadjusted hazard ratio [HR] 1.27; 95% confidence interval [CI] 1.10-1.46). Black women were less likely than white women to receive guideline-recommended care (54% compared with 68%; P<.001), and women who did not receive recommended treatment had lower survival rates than women who received recommended care. Cox proportional hazards models demonstrated no differences in black women compared with white women regarding mortality among women who were treated with guideline-recommended care (adjusted HR 1.04; 95% CI 0.85-1.26), or among women who received incomplete treatment (adjusted HR 1.09; 95% CI 0.89-1.34). The survival analysis of patients matched by propensity score confirmed these analyses. CONCLUSIONS: Differences in rates of treatment with guideline-recommended care are associated with black-white mortality disparities among women with advanced epithelial ovarian cancer. LEVEL OF EVIDENCE: III.
Thomas SG, Sato HR, Glantz JC, et al. Prevalence of symptomatic pelvic floor disorders among gynecologic oncology patients. Obstet Gynecol. 2013; 122(5):976-80 [PubMed] Related Publications
OBJECTIVE: To describe the prevalence of urinary incontinence and pelvic organ prolapse (POP) in patients with gynecologic cancer before cancer treatment. METHODS: A screening questionnaire on pelvic floor dysfunction was administered as part of the baseline health questionnaire to 549 consecutive new patients presenting to a gynecologic oncology practice. Patients were asked whether they felt a bulge from their vagina or experienced loss of urine associated with activity or urge to urinate. The prevalence of urinary incontinence, POP, or both was determined for each malignancy and benign conditions. χ2 analyses and logistic regression were used to assess significance of differences. RESULTS: Among the 347 women with a gynecologic malignancy, 49.9% women had uterine, 21.0% ovarian, and 14.4% cervical cancer. More than half of the patients with cancer reported baseline urinary incontinence (UI) and 10.9% felt a bulge from their vagina. Approximately 19% of these women had moderate-to-severe symptoms. The prevalence of baseline UI (P=.86) and POP (P=.08) did not differ by gynecologic cancer nor did they differ compared with women with benign gynecologic conditions (UI P=.89, POP P=.20). Logistic regression demonstrated an association between incontinence symptoms and increased age and body mass index (BMI). CONCLUSIONS: Women with gynecologic cancer show high prevalence of symptomatic POP and UI. Age and BMI are risk factors for UI. Coordinated surgical intervention to address both the malignancy and pelvic floor dysfunction could be considered in select patients to enhance postoperative quality of life and to reduce the economic and quality-of-life costs of multiple surgeries. LEVEL OF EVIDENCE: II.
Kim CH, Khoury-Collado F, Barber EL, et al. Sentinel lymph node mapping with pathologic ultrastaging: a valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion. Gynecol Oncol. 2013; 131(3):714-9 [PubMed] Article available free on PMC after 01/12/2014 Related Publications
OBJECTIVE: To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging. METHODS: All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells. RESULTS: Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion. CONCLUSIONS: Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.