Ovarian Cancer
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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.

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Information for Patients and the Public
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Latest Research Publications

Information Patients and the Public (21 links)

Information for Health Professionals / Researchers (12 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Sarwar S, Siddiqui N, Ather S, et al.
Outcomes among patients with sex cord stromal tumour of ovary: experience from Pakistan.
J Ayub Med Coll Abbottabad. 2014 Jul-Sep; 26(3):389-92 [PubMed] Related Publications
BACKGROUND: Ovarian sex cord-stromal tumours (SCST) are relatively uncommon neoplasms that account for approximately 5-7% of all primary ovarian tumours. The aim was to report experience with sex cord stromal tumours (SCST) of ovary in a low and middle income country.
METHODS: Clinical records of 56 patients with histopathologically-established SCST of ovary admitted to a tertiary care cancer hospital in Pakistan between April 1995 and December 2011 were reviewed.
RESULTS: Median age at presentation was 41 years (Range 4-77). Forty one (73%) patients were premenopausal and 15 (26.8%) were postmenopausal. The most common presenting complaint was abdominal pain (28.1%). Thirty seven patients (66%) had stage-I, 2 had stage II and II each, and 15 (26.8%) had stage IV disease. Five years survival in patients with early stage (stages I & II) was 91% while in those in the late stage (II & IV) was 84% (p=0.79). Histopathologically, 49 patients (85.7%) had Granulosa cell tumour, and 7 (12.5%) had Sertoli Lyedig cell tumour. CA-125 was high only in 8 patients (14.3%). Adjuvant chemotherapy was give in 16 (28.6%). Thirty six (64%) were disease free at last follow up, 10 (18%) succumbed to disease and 10 (18%) were alive with disease. On univariate and multivariate analyses, late stage at presentation was the sole factor significantly associated with mortality.
CONCLUSION: Ovarian sex cord-stromal tumours of ovary are relatively uncommon malignancies with good prognosis if diagnosed early and treated adequately. Survival in our study was comparable to those reported elsewhere. Among various factors, late stage of tumour at presentation was found to be the only factor significantly associated with mortality.

Ceccaldi R, Liu JC, Amunugama R, et al.
Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair.
Nature. 2015; 518(7538):258-62 [PubMed] Related Publications
Large-scale genomic studies have shown that half of epithelial ovarian cancers (EOCs) have alterations in genes regulating homologous recombination (HR) repair. Loss of HR accounts for the genomic instability of EOCs and for their cellular hyper-dependence on alternative poly-ADP ribose polymerase (PARP)-mediated DNA repair mechanisms. Previous studies have implicated the DNA polymerase θ (Polθ also known as POLQ, encoded by POLQ) in a pathway required for the repair of DNA double-strand breaks, referred to as the error-prone microhomology-mediated end-joining (MMEJ) pathway. Whether Polθ interacts with canonical DNA repair pathways to prevent genomic instability remains unknown. Here we report an inverse correlation between HR activity and Polθ expression in EOCs. Knockdown of Polθ in HR-proficient cells upregulates HR activity and RAD51 nucleofilament assembly, while knockdown of Polθ in HR-deficient EOCs enhances cell death. Consistent with these results, genetic inactivation of an HR gene (Fancd2) and Polq in mice results in embryonic lethality. Moreover, Polθ contains RAD51 binding motifs and it blocks RAD51-mediated recombination. Our results reveal a synthetic lethal relationship between the HR pathway and Polθ-mediated repair in EOCs, and identify Polθ as a novel druggable target for cancer therapy.

Related: FANCD2

Falconer H, Yin L, Grönberg H, Altman D
Ovarian cancer risk after salpingectomy: a nationwide population-based study.
J Natl Cancer Inst. 2015; 107(2) [PubMed] Related Publications
BACKGROUND: Recent genetic and morphologic studies have challenged the traditional view on the pathogenesis of ovarian cancer; suggesting that ovarian cancer predominantly arises within the fallopian tubes or the uterus. We hypothesize that surgical removal of the fallopian tubes is associated with a reduced risk for ovarian cancer.
METHODS: In this population-based cohort study, we used data on women with previous surgery on benign indication (sterilization, salpingectomy, hysterectomy, and bilateral salpingo-oophorectomy [BSO], hysterectomy; n = 251465) compared with the unexposed population (n = 5449119) between 1973 and 2009 and analyzed with Cox regression models. The effects of one- and two-sided salpingectomy were considered in a subanalysis. All statistical tests were two-sided.
RESULTS: There was a statistically significantly lower risk for ovarian cancer among women with previous salpingectomy (HR = 0.65, 95% CI = 0.52 to 0.81) when compared with the unexposed population. In addition, statistically significant risk reductions were observed among women with previous hysterectomy (HR = 0.79, 95% CI = 0.70 to 0.88), sterilization (HR = 0.72, 95% CI = 0.64 to 0.81), and hysterectomy with BSO (HR = 0.06, 95% CI = 0.03 to 0.12). Bilateral salpingectomy was associated with a 50% decrease in risk of ovarian cancer compared with the unilateral procedure (HR = 0.35, 95% CI = 0.17 to 0.73, and 0.71, 95% CI = 0.56 to 0.91, respectively).
CONCLUSION: Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population.

Mehboob M, Naz S, Zubair M, Kasi MA
Giant ovarian cyst--an unusual finding.
J Ayub Med Coll Abbottabad. 2014 Apr-Jun; 26(2):244-5 [PubMed] Related Publications
A 16 year old unmarried girl presented with complaints of abdominal distension, vomiting, constipation, difficulty in breathing and restlessness. On examination abdomen was grossly distended with fluid thrill. Ultrasonographic examination revealed that there was a huge cystic collection with internal debris, multiple septations involving the whole abdomen and pelvis originating from right ovary. The left ovary was normal. Her laparatomy was done. A giant ovarian cyst measuring 45 x 32 x 28 cm, which weighed 18 Kg (almost 1/3 of whole body weight), was removed as such like a yoyo balloon. Post-operative recovery was smooth. Histopathological examination revealed that it was mucinous cystadenoma.

Wang H, Paczulla A, Lengerke C
Evaluation of stem cell properties in human ovarian carcinoma cells using multi and single cell-based spheres assays.
J Vis Exp. 2015; (95):e52259 [PubMed] Related Publications
Years of research indicates that ovarian cancers harbor a heterogeneous mixture of cells including a subpopulation of so-called "cancer stem cells" (CSCs) responsible for tumor initiation, maintenance and relapse following conventional chemotherapies. Identification of ovarian CSCs is therefore an important goal. A commonly used method to assess CSC potential in vitro is the spheres assay in which cells are plated under non-adherent culture conditions in serum-free medium supplemented with growth factors and sphere formation is scored after a few days. Here, we review currently available protocols for human ovarian cancer spheres assays and perform a side-by-side analysis between commonly used multi cell-based assays and a more accurate system based on single cell plating. Our results indicate that both multi cell-based as well as single cell-based spheres assays can be used to investigate sphere formation in vitro. The more laborious and expensive single cell-based assays are more suitable for functional assessment of individual cells and lead to overall more accurate results while multi cell-based assays can be strongly influenced by the density of plated cells and require titration experiments upfront. Methylcellulose supplementation to multi cell-based assays can be effectively used to reduce mechanical artifacts.

Committee opinion no. 620: Salpingectomy for ovarian cancer prevention.
Obstet Gynecol. 2015; 125(1):279-81 [PubMed] Related Publications
Ovarian cancer has the highest mortality rate out of all types of gynecologic cancer and is the fifth leading cause of cancer deaths among women. Current attempts at screening for ovarian cancer have been unsuccessful and are associated with false-positive test results that lead to unnecessary surgery and surgical complications. Prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. Randomized controlled trials are needed to support the validity of this approach to reduce the incidence of ovarian cancer. The approach to hysterectomy or sterilization should not be influenced by the theoretical benefit of salpingectomy. Surgeons should continue to observe and practice minimally invasive techniques.

Win AK, Reece JC, Ryan S
Family history and risk of endometrial cancer: a systematic review and meta-analysis.
Obstet Gynecol. 2015; 125(1):89-98 [PubMed] Related Publications
OBJECTIVE: To obtain precise estimates of endometrial cancer risk associated with a family history of endometrial cancer or cancers at other sites.
DATA SOURCES: For the systematic review, we used PubMed to search for all relevant studies on family history and endometrial cancer that were published before December 2013. Medical Subject Heading terms "endometrial neoplasm" and "uterine neoplasm" were used in combination with one of the key phrases "family history," "first-degree," "familial risk," "aggregation," or "relatedness."
METHODS OF STUDY SELECTION: Studies were included if they were case-control or cohort studies that investigated the association between a family history of cancer specified to site and endometrial cancer. Studies were excluded if they were review or editorial articles or not translated into English or did not define family history clearly or used spouses as control participants.
TABULATION, INTEGRATION, AND RESULTS: We included 16 studies containing 3,871 women as cases and 49,475 women as controls from 10 case-control studies and 33,510 women as cases from six cohort studies. We conducted meta-analyses to estimate the pooled relative risk (95% confidence interval [CI]) of endometrial cancer associated with a first-degree family history of endometrial, colorectal, breast, ovarian, and cervical cancer to be: 1.82 (1.65-1.98), 1.17 (1.03-1.31), 0.96 (0.88-1.04), 1.13 (0.85-1.41), and 1.19 (0.83-1.55), respectively. We estimated cumulative risk of endometrial cancer to age 70 years to be 3.1% (95% CI 2.8-3.4) for women with a first-degree relative with endometrial cancer and the population-attributable risk to be 3.5% (95% CI 2.8-4.2).
CONCLUSION: Women with a first-degree family history of endometrial cancer or colorectal cancer have a higher risk of developing endometrial cancer than those without a family history. This study is likely to be of clinical relevance to inform women of their risk of endometrial cancer.

Related: Breast Cancer Colorectal (Bowel) Cancer Endometrial (Uterus) Cancer Endometrial Cancer Cervical Cancer

Miyamoto M, Takano M, Goto T, et al.
Ovarian yolk sac tumor associated with pregnancy: a case report and review of the literature.
Eur J Gynaecol Oncol. 2014; 35(6):738-40 [PubMed] Related Publications
BACKGROUND: Ovarian yolk sac tumor (YST) that is diagnosed during pregnancy is extremely rare.
CLINICAL CASE: A 22-year-old pregnant woman diagnosed with Stage IIIc YST at 17 weeks of gestation is presented. A 20-cm multilocular cystic tumor containing solid components with massive ascites was detected. Subsequently she underwent left salpingo-oophorectomy and cytoreductive surgery for peritoneal dissemination at 18 weeks of gestation, and the tumors were diagnosed as YST. After vaginal termination at 20 weeks of gestation, she received five cycles of combination therapy with bleomycin, etoposide, and cisplatin. There was no evidence of recurrence at 85 months after primary treatment.
CONCLUSION: Considering the rarity, treatment strategy for advanced-staged YST should be further investigated in international collaborative studies.

Related: Breast cancer in pregnancy

Cha MY, Roh HJ, You SK, et al.
Meigs' syndrome with elevated serum CA 125 level in a case of ovarian fibrothecoma.
Eur J Gynaecol Oncol. 2014; 35(6):734-7 [PubMed] Related Publications
Meigs' syndrome is the association of benign ovarian tumor, pleural effusion, and ascites. Meigs' syndrome with marked elevated CA 125 is a rare clinical entity and only 42 cases have been reported. Although there is difficulty in discerning the diagnosis of Meigs' syndrome from that of an ovarian malignancy, it should be considered in the differential diagnosis in postmenopausal patients with an ovarian mass, hydrothorax, ascites, and elevated CA 125. In this report, the authors present the case of a 52-year-old postmenopausal woman with ovarian fibrothecoma, pleural effusion, ascites, and elevated CA 125 (319.2 IU/ml). Exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy was performed, and the pathologic diagnosis was ovarian fibrothecoma. After the surgery, the pleural effusion disappeared spontaneously and the CA 125 became normal. The authors also summarized other cases of Meigs' syndrome with elevated CA 125, and reviewed the mechanism of elevation of CA 125, ascites, and pleural effusion.

Carta G, Accurti V, Di Nicola M, et al.
Uterine endometrioid carcinoma with focal area of choriocarcinomatous differentiation: case report.
Eur J Gynaecol Oncol. 2014; 35(6):731-3 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: An endometrioid carcinoma coexisting with choriocarcinomatous differentiation is an uncommon event with an aggressive clinical course and a poor prognosis.
MATERIALS AND METHODS: The authors describe an endometrioid carcinoma of the endometrium provided with a focus of choriocarcinoma-like cells in a 50-year-old menstruated woman with a history of abnormal uterine bleeding. A total bilateral hystero-annessectomy was performed.
RESULTS: Histopathologic study showed endometrioid adenocarcinoma limited to the endometrium with a single microinvasive (< one mm) choriocarcinomatous focus. Immunohistochemistry established intense reactivity of tumor cells for CK 7 and AE1/AE3, for beta-human chorionic gonadotropin (beta-hCG), and for HER2 confirming the diagnosis. During the clinical course and follow-up, serum levels of beta-hCG were always negative. Up to date the patient is still alive with no evidence of disease.
CONCLUSION: Even if endometrioid carcinoma with choriocarcinomatous differentiation is considered highly malignant, occasionally it may have a good prognosis, especially when a non-invasive behaviour is detected together with negative serum beta-hCG levels.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Zhu G, Hong L, Wang S, et al.
Comparison of two kinds of orthotopic xenograft models for human ovarian cancer.
Eur J Gynaecol Oncol. 2014; 35(6):724-7 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to compare the characteristics of two orthotopic xenograft models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3.
MATERIALS AND METHODS: Tumor tissues and cell line OVCAR3 of human epithelial ovarian cancer were grown in subcutaneous tissue and the subcutaneous tumor source was fetched and inoculated in ovarian capsule of nude mice under microscope to establish the orthotopic implantation model. At four and eight weeks after modeling, the orthotopic tumor formation rate, tumor diameter, metastasis rate outside the ovary, incidence rate of ascites, and CA125 levels in the two models were observed.
RESULTS: The orthotopic tumor formation rate in the solid tumor slices group (60.0%) was significantly lower than that in the cell line group (85.0%, p < 0.05). However, the tumor diameter, metastasis rate outside the ovary, incidence rate of ascites, and CA125 levels in the solid tumor slices group (2.4 +/- 0.61 cm, 75.0%, 50.0%, and 80.13 +/- 11.26 U/ml, respectively) were remarkably higher than those in the cell line group (1.6 +/- 0.53 cm, 52.9%, 29.4%, and 36.5 +/- 6.71 U/ml, respectively) (p < 0.05, respectively).
CONCLUSION: There are differences between the two orthotopic xenograft models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3. The biological characteristics of the solid tumor slices model are more similar to human ovarian cancer.

Numanoglu C, Ulker V, Kuru O, et al.
Borderline epithelial ovarian tumors: a single center experience.
Eur J Gynaecol Oncol. 2014; 35(6):692-5 [PubMed] Related Publications
AIM: To evaluate the clinical outcomes of the patients treated for borderline ovarian tumor (BOT).
MATERIALS AND METHODS: In this retrospective study, records of the patients between November 2001 and December 2012 who underwent surgery and whose final pathological diagnosis were BOT were retrieved.
RESULTS: During the study period, 78 patients were diagnosed as BOT. The patho- logical diagnoses of the tumors were serous in 26 (33.3%) and mucinous in 52 patients (66.6 %), respectively. Accuracy of frozen section diagnosis was observed in 63 of 89 patients (70.7%). Sixty-eight women (87.1%) underwent complete staging procedure. According to final pathological diagnoses, Stage IA, IB, and IC were found in 52 (67%), five (6.5%), and seven (9%) patients, respectively. FIGO Stages IIC and IIIC were found in one case in each (1.25%). Remaining 12 patients were classified as unstaged (15%). The median follow-up time was 63 months. The authors observed only one recurrence (1.3%) and that patient died of disease.
CONCLUSION: The survival rate in patients with BOTs confined to the ovary is excellent. Surgical staging procedure can be omitted in the patients with grossly apparent Stage I mucinous tumors.

Su Z, Hou XK, Wen QP
Propofol induces apoptosis of epithelial ovarian cancer cells by upregulation of microRNA let-7i expression.
Eur J Gynaecol Oncol. 2014; 35(6):688-91 [PubMed] Related Publications
OBJECTIVE: Propofol is one of the extensively and commonly used intravenous anaesthetic agents. The aims of the current study were to evaluate effects of propofol on the behavior of human epithelial ovarian cancer (EOC) cells and role of miR-let-7i in these effects.
MATERIALS AND METHODS: The effects of propofol on cell proliferation and apoptosis were detected by MTT assays and flow cytometry. Real-time polymerase chain reaction (PCR) was used to assess miR-let-7i expression in human EOC cells OVCAR-3 with or without propofol treatment. Finally, the authors evaluated the effect ofmiR-let-7i on propofol-induced anti-tumor activity using anti-miR-let-7i.
RESULTS: Propofol inhibited the proliferation of OVCAR-3 cells in a dose- and time-dependent manner. After exposure to propofol for 24 hours, OVCAR-3 cells showed increased apoptosis and increased expression of miR-let-7i. Finally, anti-miR-let-7i reversed the effect of propofol on cell proliferation and apoptosis.
CONCLUSIONS: Propofol can effectively inhibit proliferation and induce apoptosis of EOC cells and modulation of miR-let-7i possibly contributes to the anti-tumor action of propofol.

Related: Apoptosis MicroRNAs

Wang L, Wang B, Fang M, et al.
Identification of microRNAs and target genes involved in serous ovarian carcinoma and their influence on survival.
Eur J Gynaecol Oncol. 2014; 35(6):655-61 [PubMed] Related Publications
AIMS: To identify the expression of key microRNAs and their predicted target genes involved in serous ovarian carcinoma (SOC) and correlation between miRNAs and prognosis.
MATERIALS AND METHODS: The authors used quantitative polymerase chain reaction (qPCR) to detect the expression of miR-145, miR-143, miR-146a, miR-93, miR-29a, miR-18a, and miR-200a in tissues of 56 primary SOC patients and 30 benign lesion patients. Four protein (MUC1, FAP, MMP2, MMP9) expressions were identified by western blotting and immunohistochemical stain. The Kaplan-Meier method was used to estimate the relationship of these miRNAs with overall survival rate.
RESULTS: In SOC tissue, expression of miR-200a, miR-93, miR-146a, and miR-18a were up-regulated, while miR-145, miR-143, miR-29a were down-regulated. MUC1, FAP, MMP2, and MMP9 were overexpressed in SOC. MiR-143 or miR-145 higher expressed patients had significantly higher overall survival (OS) rates, while miR-93 or miR-200a lower expressed patients also had higher OS rates.
DISCUSSION: These results suggested that several miRNAs and their regulated target transcripts may have important roles in the initiation and development of SOC. MiR-145/miR-143, miR-200a, and miR-93 could be used as prognostic biomarkers.

Related: MicroRNAs

Ugianskiene A, Grove A, Soegaard-Andersen E
Adult granulosa cell tumor of the ovary: a retrospective study of 37 cases.
Eur J Gynaecol Oncol. 2014; 35(6):621-4 [PubMed] Related Publications
AIM: to evaluate the recurrence rate and the overall survival in women with adult granulosa cell tumor (AGCT), who were treated at the Department of Obstetrics and Gynecology, Aalborg University Hospital during the period January 1985 to January 2010.
MATERIALS AND METHODS: Data from 38 women with AGCT were collected retrospectively. The histological slides were re-evaluated by a gynecologic pathologist. Surgical and pathological characteristics were analyzed. Results: Thirty-seven women with AGCT were diagnosed. 92% were diagnosed in FIGO Stage I and 8% in Stage II. The majority of patients (27 patients, 73%) were treated with total abdomi- nal hysterectomy and bilateral salpingooophorectomy. Only one patient received postoperative pelvic irradiation. The recurrence rate was 5.6%.
CONCLUSION: The recurrent rate was 5.6%, which is low according to the literature. Primary surgical treatment with radical removal of tumor seemed to be appropriate treatment.

Owusu-Darko S, Rauh-Hain JA, Horowitz NS, et al.
Comparison of outcomes in patients with early-stage mucinous endometrial cancer and those with endometrioid endometrial cancer, with and without adjuvant therapy.
J Reprod Med. 2014 Nov-Dec; 59(11-12):527-33 [PubMed] Related Publications
OBJECTIVE: To compare risk factors, treatment, and outcomes in patients with stage I/II mucinous endometrial cancer (MEC) relative to those of patients with endometrioid endometrial cancer (EEC).
STUDY DESIGN: We conducted a case-control study of patients with MEC and EEC. Patients with stage IA, IB, or II MEC treated at the 2 institutions between 01/01/1996 and 01/01/2007 were identified. Each MEC case was matched with 2 EEC controls by age, stage, grade, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model.
RESULTS: A total of 34 patients with MEC were compared to 68 controls with EEC. All patients were treated by hysterectomy and bilateral salpingo-oophorectomy. Use of adjuvant radiation therapy was similar between cases and controls. The 5-year disease-free survival (DFS) rates were not significantly different in patients with MEC when compared to those with EEC (89% vs. 92%, respectively, p = 0.2). The 5-year OS rates for patients with MEC and the control group were 95% and 96%, respectively (p = 0.1).
CONCLUSION: Patients with early-stage with early-stage MEC and EEC have similar DFS and overall survival.

Related: Endometrial (Uterus) Cancer Endometrial Cancer USA

Otake A, Yoshino K, Ueda Y, et al.
Usefulness of duloxetine for Paclitaxel-induced peripheral neuropathy treatment in gynecological cancer patients.
Anticancer Res. 2015; 35(1):359-63 [PubMed] Related Publications
AIM: The present study aimed at evaluating the usefulness and adverse effects of duloxetine treatment for paclitaxel-induced peripheral neuropathy in gynecological cancer patients.
PATIENTS AND METHODS: Medical records of gynecological cancer patients treated with duloxetine were retrospectively studied to evaluate the drug's efficacy for paclitaxel-induced peripheral neuropathy.
RESULTS: RESULTS from 25 patients showed that an improved response was observed in 14 (56%). By univariate and multivariate analysis, the patient's age, tumor origin, regimen of chemotherapy, accumulated doses of paclitaxel or carboplatin, previous medication, maintenance dosage and timing of treatment with duloxetine were found not to be associated with the effectiveness of duloxetine treatment. Adverse effects with duloxetine were mild and well-tolerated.
CONCLUSION: As an option, duloxetine can be effectively used for paclitaxel-induced peripheral neuropathy in patients with gynecological cancers, irrespective of patients' age, origin of the tumor, regimen of chemotherapy, or previous medication.

Related: Paclitaxel

Dobrosz Z, Paleń P, Stojko R, et al.
Clear cell carcinoma derived from an endometriosis focus in a scar after a caesarean section--a case report and literature review.
Ginekol Pol. 2014; 85(10):792-5 [PubMed] Related Publications
Endometriosis is defined as the occurrence of endometrial glands and endometrial stromal cells outside their typical localization within the uterus. Malignant transformation of endometriosis foci in a scar after a caesarean section (cc) is very rare--until 2013 (in a span of 40 years), about 40 such cases have been described. In our article, we describe a case of a 42-year-old woman with a tumour localized in a scar after a caesarean section. The tumour was diagnosed as clear cell carcinoma derived from an endometriosis focus. The long time interval--17 years in average (from 3 to 39 years) between the surgery (cesarean section in most cases) and the tumor diagnosis is characteristic. In the case we describe, the patient was diagnosed 16 years after the endometriosis focus in the scar had arised. Even though endometriosis is a benign lesion, it has many features distinctive for invasive carcinoma; it may itself undergo a malignant transformation as well as increase the risk of endometrial carcinoma or clear cell ovarian carcinoma. Maybe in future, more exhaustive studies will allow establishing a therapeutic protocol in patients with extra-ovarian malignant transformation of endometriosis foci.

Özgül N, Köse MF, Keskin HL, et al.
Addition of epirubicin to conventional chemotherapy in patients with advanced ovarian cancer: sequential therapy -a retrospective evaluation. .
Turk J Med Sci. 2014; 44(2):212-9 [PubMed] Related Publications
AIM: To evaluate the effectiveness of the addition of epirubicin to conventional chemotherapy as a first-line therapy for stage III-IV epithelial ovarian cancer.
MATERIALS AND METHODS: A total of 132 patients who had undergone primary cytoreductive surgery between January 1998 and March 2003 were enrolled in the study. Twenty-four cases were excluded. Out of the remaining 108 subjects, 35 received epirubicin/paclitaxel/ carboplatin (Group EPC) and 73 were treated with paclitaxel/platinum (cisplatin.or carboplatin) (Group PC).
RESULTS: The median follow-up period was 66.5 months. The clinical complete response was 94% in the EPC group and 97% in the PC group. The recurrence rate in the first 6 months after treatment was significantly higher in the PC than the EPC group (47% vs. 23%, P = 0.018). Triplet chemotherapy was not found to improve 2- and 5-year disease-free survival (DFS) statistically. No significant difference in overall survival was observed between the 2 groups (80% vs. 83% at 2 years and 56% vs. 57% at 5 years for the PC and the EPC group, respectively). The main toxicity in both groups was hematological, and it was particularly severe in the EPC group.
CONCLUSION: The addition of epirubicin to the standard treatment protocol yielded an improvement in the DFS rate that was not statistically significant and caused a tolerable increase in toxicity.

Related: Carboplatin Cisplatin Epirubicin Paclitaxel

Ahmed QF, Gattoc L, Al-Wahab Z, et al.
Vanishing endometrial cancer in hysterectomy specimens: a myth or a fact.
Am J Surg Pathol. 2015; 39(2):221-6 [PubMed] Related Publications
The incidence of endometrial cancers diagnosed on biopsy that have no residual cancer identified at hysterectomy is not well studied. The aim of our study was to determine the incidence and long-term follow-up of this "vanishing cancer" phenomenon. All slides from the initial biopsy/curettage and hysterectomy specimens were reviewed and the diagnosis confirmed by a gynecologic pathologist. The entire endometrium was serially sectioned and submitted for histologic examination. Clinical and pathologic variables were analyzed, including patient demographics, tumor histologic type and grade, stage, biopsy method, adjuvant therapy, surgical procedure, recurrence, and disease-specific survival. We identified 23 biopsy-proven cases of endometrial cancer with no residual disease on hysterectomy specimen. Of the 23 patients, 15 (65.2%) were diagnosed as endometrioid, 6 (26%) serous, 1 clear cell (4.3%), and 1 (4.3%) serous intraepithelial carcinoma. Seventeen underwent dilatation and curettage, and 6 had endometrial biopsy as the primary procedure. The median follow-up was 8.8 years (range, 1.2 to 17 y). Only 2 cases with serous carcinoma underwent adjuvant chemotherapy, and none received radiation therapy. Only 1 patient died of disease after 27 months and was diagnosed as FIGO grade II endometrioid carcinoma on dilatation and curettage. The inability to identify cancer in a hysterectomy specimen for biopsy-confirmed carcinoma does not indicate technical failure. Although there is no specific standard treatment for patients with "vanishing endometrial cancer," the prognosis is excellent; however, close follow-up is suggested.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Gao X, Liu Y, Deeb D, et al.
Anticancer activity of pristimerin in ovarian carcinoma cells is mediated through the inhibition of prosurvival Akt/NF-κB/mTOR signaling.
J Exp Ther Oncol. 2014; 10(4):275-83 [PubMed] Free Access to Full Article Related Publications
Pristimerin isaquinonemethidetriterpenoidthathasshown anticancer activity against some cancer types. However, the antitumor effects of pristimerin (PM) in ovarian cancer cells have not been adequately studied. The objective of the present study was to determine the anticancer activity and its mechanism of action in human ovarian carcinoma cell lines. PM strongly inhibited the proliferation of ovarian cancer cells by inducing apoptosis characterized by increased annexin V-binding, cleavage of poly (ADP-ribose) polymerase (PARP-1) and procaspases-3, -8 and -9. Furthermore, PM caused mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho-mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with PM. Treatment with PM also inhibited the expression of NF-κB-regulated antiapoptotic Bcl-2, Bcl-xL, c-IAP1 and survivin. Thus, our data showing potent antiproliferative and apoptosis-inducing activity of PM in ovarian carcinoma cells through the inhibition of AKT/ NF-κB/ mTOR signaling pathway warrant further investigation of PM for the management of ovarian cancer.

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Guzel AI, Yalinkaya A, Alomeroglu M
A rare case of acute abdomen: torsionated ovarian myoma.
J Exp Ther Oncol. 2014; 10(4):255-7 [PubMed] Related Publications
Ovarian leiomyoma is a rare ovarian tumor and also rare cause of acute abdomen. A 64 year old, postmenopausal woman applied to our clinic with severe acute abdominal pain. On abdominal examination, there were abdominal tenderness, defense and rebound. On ultrasonographic examination, we detected a 6 cm of pelvic mass. Because she had acute abdomen we performed laparotomy by midline incision and excised a 6cm ovarian mass on right ovary. The mass had been reported as ovarian leiomyoma on frozen section by pathology department.

Chen CK, Lee MY, Lin WL, et al.
A qualitative study comparing the assay performance characteristics between the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists HER2 scoring methods in mucinous epithelial ovarian cancer.
Medicine (Baltimore). 2014; 93(27):e171 [PubMed] Related Publications
The remarkable success of trastuzumab and other newly developed anti-HER2 (human epidermal growth factor receptor 2) therapies in breast, gastric, or gastroesophageal junction cancer patients has supported us to investigate the HER2 status and its possible therapeutic implication in mucinous epithelial ovarian cancer (EOC). However, there is currently no standardization of HER2 scoring criteria in mucinous EOC. In this study, we aimed to compare both the assay performance characteristics of the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists scoring methods. Forty-nine tissue microarray samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using the 2007 and the 2013 criteria, respectively. The overall concordance between IHC and FISH by the 2007 criteria was 97.92 % (kappa = 0.921), and that by the 2013 criteria was 100% (kappa = 1.000). The percentage of Her2 FISH-amplified cases showed an increasing trend significantly through their corresponding HER2 IHC ordinals by the 2007 and the 2013 criteria, respectively (P < 0.001, P < 0.001). After excluding equivocal cases, the specificity (100%) and positive predictive value (100%) were unchanged under either the 2007 or the 2013 criteria. The sensitivity (100%), negative predictive value (NPV) (100%), and accuracy (100%) of HER2 IHC were higher under the 2013 criteria than those (sensitivity 87.5%, NPV 97.6%, and accuracy 97.9%) under the 2007 criteria. Of the total 49 cases, the number (n = 4) of HER2 IHC equivocal results under the 2013 criteria was 4-fold higher than that (n = 1) under the 2007 criteria (8.16% vs 2.04%). Conclusively, if first tested by IHC, the 2013 criteria caused more equivocal HER2 IHC cases to be referred to Her2 FISH testing than the 2007 criteria. That decreased the false-negative rate of HER2 status and increased the detection rates of HER2 positivity in mucinous EOC.

Related: ERBB2 (HER2) FISH

Chaluvally-Raghavan P, Zhang F, Pradeep S, et al.
Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers.
Cancer Cell. 2014; 26(6):863-79 [PubMed] Article available free on PMC after 08/12/2015 Related Publications
Small noncoding miRNAs represent underexplored targets of genomic aberrations and emerging therapeutic targets. The 3q26.2 amplicon is among the most frequent genomic aberrations in multiple cancer lineages including ovarian and breast cancers. We demonstrate that hsa-miR-569 (hereafter designated as miR569), which is overexpressed in a subset of ovarian and breast cancers, at least in part due to the 3q26.2 amplicon, alters cell survival and proliferation. Downregulation of TP53INP1 expression by miR569 is required for the effects of miR569 on survival and proliferation. Targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to cisplatin by increasing cell death both in vitro and in vivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.

Related: Breast Cancer Chromosome 3 Cisplatin MicroRNAs

Menon U, Talaat A, Rosenthal AN, et al.
Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening.
BJOG. 2014; 121 Suppl 7:35-9 [PubMed] Related Publications
OBJECTIVE: To assess the performance of ultrasonography in a multimodal ovarian cancer screening strategy.
DESIGN: Prospective ovarian cancer screening trial between December 1986 and June 1993.
SETTING: General practice, occupational health departments and an ovarian cancer screening clinic at a London teaching hospital.
POPULATION: Postmenopausal women, ≥ 45 years with a raised CA125.
METHODS: Volunteers with a CA125 ≥ 30 U/mL underwent a pelvic ultrasound. Scans were classified as normal, abnormal (ovarian volume ≥ 8.8 mL) or equivocal (normal volume with abnormal morphology). Abnormal ovarian morphology was subclassified as simple cyst (single, thin walled cyst with no septa or papillary projections) or complex (all other abnormalities). Volunteers with abnormal scans were referred for a gynaecological opinion. Follow up was via the cancer registry and postal questionnaires.
MAIN OUTCOME MEASURES: Sensitivity, specificity and positive predictive value of different ultrasound criteria for detection of index cancer (e.g. primary invasive epithelial carcinoma of the ovary and fallopian tube).
RESULTS: Seven hundred and forty-one women underwent 1219 scans and 20 index cancers occurred during a median follow up of 6.8 years. The sensitivity for detection of ovarian cancer of different ultrasound criteria was 100% for abnormal morphology, 89.5% for abnormal volume and 84% for complex morphology. The highest specificity (97%) and positive predictive value (37.2%) was achieved using complex morphology.
CONCLUSION: A variety of ultrasound criteria can achieve high sensitivity, specificity and positive predictive value for index cancers in postmenopausal women with an elevated CA125. Use of ovarian morphology to interpret ultrasound may increase sensitivity and use of complex ovarian morphology may increase the positive predictive value.

Related: Cancer Screening and Early Detection

van Kruchten M, de Vries EF, Arts HJ, et al.
Assessment of estrogen receptor expression in epithelial ovarian cancer patients using 16α-18F-fluoro-17β-estradiol PET/CT.
J Nucl Med. 2015; 56(1):50-5 [PubMed] Related Publications
UNLABELLED: The estrogen receptor α (ERα) is expressed in approximately 70% of ovarian cancer tumors. PET of tumor ERα expression with the tracer 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) may be valuable to select ovarian cancer patients for endocrine therapy. The aim of this study was to evaluate the feasibility of (18)F-FES PET to determine tumor ERα expression noninvasively in epithelial ovarian cancer patients.
METHODS: (18)F-FES PET/CT was performed shortly before cytoreductive surgery. Tumor (18)F-FES uptake was quantified for all lesions 10 mm or greater on CT and expressed as maximum standardized uptake value. (18)F-FES PET/CT findings were compared with histology and immunohistochemistry for ERα, ERβ, and progesterone receptor. Receptor expression was scored semiquantitatively using H-scores (percentage of positive tumor cells × staining intensity). The optimum threshold to discriminate ER-positive and -negative lesions was determined by receiver-operating-characteristic analysis.
RESULTS: In the 15 included patients with suspected ovarian cancer, 32 measurable lesions greater than 10 mm were present on CT. Tumor (18)F-FES uptake could be quantified for 28 lesions (88%), and 4 lesions were visible but nonquantifiable because of high uptake in adjacent tissue. During surgery, histology was obtained of 23 of 28 quantified lesions (82%). Quantitative (18)F-FES uptake correlated with the semiquantitative immunoscore for ERα (ρ = 0.65, P < 0.01) and weakly with progesterone receptor expression (ρ = 0.46, P = 0.03) and was not associated with ERβ expression (ρ = 0.21, P = 0.33). The optimum threshold to discriminate ERα-positive and ERα-negative lesions was a maximum standardized uptake value greater than 1.8, which provided a 79% sensitivity, 100% specificity, and area under the curve of 0.86 (95% confidence interval, 0.70-1.00). In 2 of 7 patients with cytology/histology available at primary diagnosis and at debulking surgery, immunohistochemical ERα expression had changed over time. (18)F-FES PET was in accordance with histology at debulking surgery but not at primary diagnosis, indicating that (18)F-FES PET could provide reliable information about current tumor ERα status.
CONCLUSION: (18)F-FES PET/CT can reliably assess ERα status in epithelial ovarian cancer tumors and metastases noninvasively. Evaluation of the predictive value of (18)F-FES PET/CT for endocrine therapy in epithelial ovarian cancer patients is warranted.

Luo JR, Xie CB, Li ZH
Treatment for malignant struma ovarii in the eyes of thyroid surgeons: a case report and study of Chinese cases reported in the literature.
Medicine (Baltimore). 2014; 93(26):e147 [PubMed] Related Publications
Malignant struma ovarii (MSO) is a rare malignant ovarian germ cell tumor that has been scarcely reported by thyroid surgeons focusing on treatment. There are no golden standards for its treatment. There has not been any Chinese case included in the English language literatures. This is the first study by collecting all Chinese cases with clinical information. We emphasize on using I therapy after operation.Presented is a case of struma ovarii with malignant histologic features who underwent definitive initial surgery of reproductive system tumors and a total thyroidectomy combined with thyroid-stimulating hormone (TSH)-suppressive therapy following treatment with I. Furthermore, a Chinese full-text database literature search for cases of MSO was performed, and advisable clinical data were collected following our treatment advice.Clinical data from 34 additional cases were compiled. As Chinese genetic background and environment are different from those of Western countries, our clinical data closely mirror theirs in some aspects. In addition, we provide a rare gene mutation type of MSO by the case from our department.Integrating literatures with the experience of thyroid surgeons, we recommend "multidisciplinary joint treatment" for MSO, namely traditional radical initial surgery of ovarian cancer and a total thyroidectomy combined with TSH-suppressive therapy following treatment with I for those who do not desire preservation of fertility.

Related: Thyroid Cancer

Plamadeala V, Kelley JL, Chan JK, et al.
A cost-effectiveness analysis of a chemoresponse assay for treatment of patients with recurrent epithelial ovarian cancer.
Gynecol Oncol. 2015; 136(1):94-8 [PubMed] Related Publications
OBJECTIVE: Clinical validation of a chemoresponse assay was recently published, demonstrating a significant increase in overall survival in recurrent ovarian cancer patients treated with therapies to which their tumor was sensitive in the assay. The current study investigates the cost effectiveness of using the assay at the time of ovarian cancer recurrence from the payer's perspective.
METHODS: Using a Markov state transition model, patient characteristics and survival data from the recent clinical study, the cumulative costs over the study horizon (71 months) for both the baseline (no assay) and intervention (assay consistent, hypothetical) cohorts were evaluated.
RESULTS: The assay consistent cohort had an incremental cost effectiveness ratio (ICER) of $6206 per life year saved (LYS), as compared to the baseline cohort. Cost-effectiveness was further demonstrated in platinum-sensitive and platinum-resistant populations treated with assay-sensitive therapies, with ICERs of $2773 per LYS and $2736 per LYS, respectively.
CONCLUSIONS: The use of a chemoresponse assay to inform treatment decisions in recurrent ovarian cancer patients has the potential to be cost-effective in both platinum-sensitive and platinum-resistant patients.

Related: USA

Chen CA, Lin H, Weng CS, et al.
Outcome of 3-day bleomycin, etoposide and cisplatin chemotherapeutic regimen for patients with malignant ovarian germ cell tumours: a Taiwanese Gynecologic Oncology Group study.
Eur J Cancer. 2014; 50(18):3161-7 [PubMed] Related Publications
BACKGROUND: The combination of bleomycin, etoposide and cisplatin (BEP) is currently the most widely used treatment for malignant ovarian germ cell tumours (MOGCTs). The aim of this study was to evaluate the efficacy and adverse effects of the 3-day BEP regimen in Taiwan. The prognostic factors of the MOGCT patients were also analysed.
PATIENTS AND METHODS: Two hundred and thirty-nine cases of MOGCTs were identified from the Taiwanese Gynecologic Oncology Group database, and 204 of those who received postoperative BEP chemotherapy were then analysed.
RESULTS: The estimated rate of no evidence of disease was 94.0% for 204 patients with adjuvant BEP regimen. Seven grade 3/4 haematological adverse effects including four subjects with neutropenia, one with pancytopenia and two with neutropenic fever were recorded in the 853 total courses of chemotherapeutic cycles. The rates of haematological and non-haematological adverse effects were 0.82% and 2.3%, respectively. No treatment-related mortality was noted. In the analysis of prognostic factors, only tumour stage had a significant impact on disease recurrence (95% confidence interval (CI), 4.2–94.4, p < 0.001) and disease-related mortality (95% CI, 2.2–163.9, p = 0.007).
CONCLUSIONS: The current 3-day adjuvant BEP regimen was effective and safe for patients with MOGCTs.

Related: Bleomycin Cisplatin Etoposide Germ Cell Tumors

Davidson B, Holth A, Hellesylt E, et al.
The clinical role of epithelial-mesenchymal transition and stem cell markers in advanced-stage ovarian serous carcinoma effusions.
Hum Pathol. 2015; 46(1):1-8 [PubMed] Related Publications
We recently identified gene signatures that allow classification of ovarian carcinoma into 5 distinct clinically relevant groups. In the present study, we investigated the clinical role of 10 protein products of the discriminating genes, with focus on epithelial-mesenchymal transition and stem cell markers. Expression of E-cadherin, N-cadherin, P-cadherin, Zeb1, HMGA2, Rab25, CD24, NCAM (CD56), Sox11, and vimentin was assessed in 100 advanced-stage (International Federation of Gynecology and Obstetrics stages III-IV) serous ovarian carcinoma effusions using immunohistochemistry. Results were analyzed for association with clinicopathological parameters, including chemotherapy response, and survival. All 10 proteins were frequently expressed in carcinoma cells. HMGA2 expression was related to older age (P = .015). HMGA2 and NCAM expression was related to stage III disease (P = .011 and P = .023, respectively), and NCAM was overexpressed in peritoneal compared with pleural effusions (P = .001). Vimentin and Zeb1 expression was significantly related to poor chemotherapy response at diagnosis (P = .005 and P = .017, respectively). The associations between NCAM and peritoneal localization and of vimentin and poor chemoresponse were retained after Bonferroni correction. NCAM expression was associated with a trend for shorter overall survival in univariate survival analysis (P = .187), but emerged as an independent prognosticator in Cox multivariate analysis (P = .042). This study identifies vimentin and Zeb1 as markers of poor chemoresponse in metastatic serous ovarian carcinoma effusions and suggests NCAM as potential prognostic marker in metastatic disease. The generally limited prognostic role of the studied markers emphasizes the difficulty in applying data obtained in studies of primary ovarian carcinomas to analyses of ovarian carcinoma effusions, reflecting the unique biology of the latter.

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