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).

Jin X, Zhu Z, Shi Y
Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis.
Bull Cancer. 2014; 101(1):E1-12 [PubMed] Related Publications
Metastasis is the most fatal characteristics of malignancy tumor, which accounted for more than 90% of tumor-related mortality. Distant organ or tissue metastasis is a sign of poor prognosis in patients with gastric cancer. Tumor cells metastasis is a very complex process including tumor cell transformation, growth, angiogenesis, invasion, dissemination and survival in the circulation, and subsequent adhesion and colonization the secondary organ or tissue. The origin of tumor cell, genetic variation, the circulatory mode and the physiological structure of the metastatic organ determines the specific sites of distant metastasis. In theory, the metastatic lesion is originated from their primary tumor, so they should have the same molecular profile with the primary tumor. But this view has been confirmed to be wrong in various tumors, including gastric cancer. The gene expression of primary gastric cancer and its metastasis have differences, which may contribute to the early diagnosis and individualized treatment of metastasis. However, the heterogeneity of tumor cells is still unclear in different metastasis lesion of gastric cancer, which will be a major focus of future research. In this review, we discuss the basic principles of cancer metastasis, the unique physiological characteristics of the various metastasis organs and the expression of different functions of gene/protein in primary and metastasis of gastric cancer. In addition, we also discuss the diagnosis, prognosis and treatment in various organ metastasis of gastric cancer.

Related: Angiogenesis and Cancer Stomach Cancer Gastric Cancer

Bayar UO, Gün BD, Ungan B, et al.
Unilateral ovarian agenesis and clear cell type epithelioid leiomyoma of uterus mimicking ovarian malignancy.
J Pak Med Assoc. 2014; 64(1):79-81 [PubMed] Related Publications
A case of unilateral absent ovary together with clear cell type epithelioid leiomyoma of uterus mimicking ovarian malignancy discovered during laparotomy is presented. Unilateral absence of an ovary is an extremely rare finding. Although the exact pathophysiological mechanism is not known, it could result from a defect in embryological development or asymptomatic torsion of ovary. Clear cell type epithelioid leiomyoma of uterus is also a rare variant, composed of round or polygonal 'clear' cells rather than typical spindle-shaped cells and ultra structurally differs from non-uterine counterparts.

Garrett LA, Growdon WB, Goodman A, et al.
Endometriosis-associated ovarian malignancy: a retrospective analysis of presentation, treatment, and outcome.
J Reprod Med. 2013 Nov-Dec; 58(11-12):469-76 [PubMed] Related Publications
OBJECTIVE: To investigate the relationship of age and tumors associated with endometriosis and outcome of different histologies of epithelial ovarian cancer arising from endometriosis.
STUDY DESIGN: We identified cases of epithelial ovarian cancers with clear cell, endometrioid, or mixed clear cell and endometrioid histologies from January 2001 to March 2009. Tumors were classified as either "arising in" endometriosis, "associated with" endometriosis or "controls" (not associated with endometriosis). We collected information regarding patient demographics, past medical history, presentation at diagnosis, treatment, and outcome.
RESULTS: Of 140 patients identified, 42 (30.0%) had clear cell, 92 (65.7%) had endometrioid, and 6 (4.3%) had mixed. Of those, 28.6% of tumors were associated with endometriosis (n = 40), 37.1% were arising in endometriosis (n = 52), and 34.3% were controls (n = 48). Premenopausal women had tumors that were more likely arising from or associated with endometriosis as compared to tumors in postmenopausal women (p = 0.005). Premenopausal patients were also more likely to present with early stage disease as compared to postmenopausal women (80.4% vs. 63.6%, p = 0.04) and better overall survival (p < 0.008). Survival analyses of the entire cohort showed that improved survival was associated with stage (p < 0.001), grade (p < 0.001), endometrioid histology (p < 0.005), and with tumors associated with or arising in endometriosis (p < 0.04). Multivariate analysis controlling for menopausal status showed the presence of endometriosis was no longer associated with a survival advantage (p = 0.08).
CONCLUSION: The association with endometriosis does appear, at least in endometrioid tumors, to provide a survival benefit. Overall, menopausal status, stage, and grade are more powerful variables associated with improved survival.

Shim SH, Lee SJ, Kim DY, et al.
A Long-term follow-up study of 91 cases with ovarian granulosa cell tumors.
Anticancer Res. 2014; 34(2):1001-10 [PubMed] Related Publications
AIM: To evaluate the prognostic factors of ovarian granulosa cell tumors (GCTs) and treatment outcomes in recurrent GCT cases.
PATIENTS AND METHODS: We retrospectively reviewed 91 patients with GCT who were treated in two tertiary Centers between 1989 and 2011.
RESULTS: Eighty patients had stage I tumors, five had stage II, and six had stage III. There were 15 cases of recurrence with a median follow-up time of 58 (3-254) months. Multivariate analysis identified greater tumor size and postoperative residual tumor as independent risk factors for recurrence. Twelve patients underwent secondary surgery at first recurrence. At a median follow-up of 50 (4-185) months from first recurrence, the 5-year survival was 60% for patients with and 100% for those without residual tumor after secondary surgery, respectively (p=0.018, log-rank test).
CONCLUSION: Complete cytoreduction is an important prognostic factor for recurrent cases as well as initial treatment of GCT.

Jeong W, Kim SB, Sohn BH, et al.
Activation of YAP1 is associated with poor prognosis and response to taxanes in ovarian cancer.
Anticancer Res. 2014; 34(2):811-7 [PubMed] Related Publications
AIM: We aimed to investigate the clinical significance of the activation of Yes-Associated Protein 1 (YAP1), a key downstream effector of Hippo tumor-suppressor pathway, in ovarian cancer.
MATERIALS AND METHODS: A gene expression signature reflecting activation of YAP1 was developed from gene expression data of 267 samples from patients with ovarian cancer. A refined ovarian cancer YAP1 signature was validated in an independent ovarian cancer cohort (n=185). Associations between the YAP1 signature and prognosis were assessed using Kaplan-Meier plots, the log-rank test, and a Cox proportional hazards model.
RESULTS: We identified a 612-gene expression signature reflecting YAP1 activation in ovarian cancer. In multivariate analysis, the signature was an independent predictor of overall survival (hazard ratio=1.66; 95% confidence interval=1.1 to 2.53; p=0.01). In subset analysis, the signature identified patients likely to benefit from taxane-based adjuvant chemotherapy.
CONCLUSION: Activation of YAP1 is significantly associated with prognosis and the YAP1 signature can predict response to taxane-based adjuvant chemotherapy in patients with ovarian cancer.

Related: Signal Transduction

Piura B, Medina L, Rabinovich A, et al.
Distinct expression and localization of TNF system in ovarian carcinoma tissues: possible involvement of TNF-α in morphological changes of ovarian cancerous cells.
Anticancer Res. 2014; 34(2):745-52 [PubMed] Related Publications
BACKGROUND/AIM: It has been previously shown that epithelial ovarian carcinoma tissues express high levels of tumor necrosis alpha (TNF-α), interleukin (IL)-6, IL-1α and IL-1β. The aim of the present study was to evaluate the localization of TNF-α and its receptors (TNFR1 and TNFR2) in different types of ovarian carcinoma tissues and the possible role of TNF in the pathogenesis of epithelial ovarian carcinoma.
MATERIALS AND METHODS: Total RNA was extracted from normal and cancerous ovarian tissues and mRNA was analyzed with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemical staining was performed with use of antibodies against human (ah)TNFR1 and TNF2.
RESULTS: TNF-α mRNA and TNFR2 mRNA levels were significantly higher in ovarian carcinoma tissues than in normal ovarian tissues, whereas TNFR1 mRNA levels were similar. TNFR1 and TNFR2 were mainly localized in the epithelial neoplastic cells of the tumor. Knocking-down TNF-α activity with αhTNF-a altered ovarian carcinoma cell morphology (with more branches) in vitro.
CONCLUSION: Our study indicates a possible role of TNF-α in epithelial ovarian carcinoma pathogenesis through TNFR2, which affects morphological changes, which may be involved ovarian cancer pathogenesis.

Related: TNF

Fagö-Olsen CL, Ottesen B, Christensen IJ, et al.
Biomarkers for predicting complete debulking in ovarian cancer: lessons to be learned.
Anticancer Res. 2014; 34(2):679-82 [PubMed] Related Publications
AIM: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients.
PATIENTS AND METHODS: The study consisted of three parts: Part I: Biomarker data obtained from mass spectrometry, baseline data and, surgical outcome were used to construct predictive indices for complete tumour resection; Part II: sera from randomly selected patients from part I were analyzed using enzyme-linked immunosorbent assay (ELISA) to investigate the correlation to mass spectrometry; Part III: the indices from part I were validated in a new cohort of patients.
RESULTS: Part I: The area under the receiver operating characteristic curve (AUC) was 0.82 for both indices. Part II: Linear regression analysis gave an R(2) value of 0.52 and 0.63 for transferrin and β2-microglobulin, respectively. Part III: The AUC of the two indices decreased to 0.64.
CONCLUSION: Our validated model based on biomarkers was unable to predict surgical outcome for patients with ovarian cancer.

Trabert B, Ness RB, Lo-Ciganic WH, et al.
Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium.
J Natl Cancer Inst. 2014; 106(2):djt431 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive.
METHODS: We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided.
RESULTS: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91).
CONCLUSIONS: Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Related: Australia USA

Andersen MR, Lowe KA, Goff BA
Value of symptom-triggered diagnostic evaluation for ovarian cancer.
Obstet Gynecol. 2014; 123(1):73-9 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
OBJECTIVE: To evaluate the potential harms and ovarian cancer outcomes associated with symptom-triggered diagnostic evaluation of all women with symptoms of ovarian cancer.
METHODS: Five thousand twelve women older than age 40 years were prospectively enrolled in a cohort study of proactive symptom-triggered diagnostic evaluation. Women who tested positive on a symptom index were offered testing with CA 125 and transvaginal ultrasonography. Results of these tests and any subsequent procedures were recorded. Assessment of ovarian cancer outcomes for all participants through Surveillance, Epidemiology, and End Results was performed 1 year after enrollment was complete.
RESULTS: A positive symptom index was found in 241 (4.8%) participating patients, and 211 (88%) underwent CA 125 testing, transvaginal ultrasound screening, or both. Twenty surgical procedures (laparoscopy, laparotomy, vaginal) were performed in the study population (0.4% of participating women). However, only six (0.12%) were performed for a suspicious ovarian mass and only four (0.08%) were performed solely as a result of study participation. A total of eight ovarian cancers were diagnosed, 31-843 days after symptom assessment (50% distant, 50% local or regional). Of the two cancers diagnosed within 6 months, one was symptom index-positive.
CONCLUSIONS: Proactive symptom-triggered diagnostic evaluation for ovarian cancer results in minimal unindicated surgery. A small number of ovarian cancers was identified solely on the basis of symptom-triggered diagnostic testing.

Chan JK, Urban R, Capra AM, et al.
Ovarian cancer rates after hysterectomy with and without salpingo-oophorectomy.
Obstet Gynecol. 2014; 123(1):65-72 [PubMed] Related Publications
OBJECTIVE: To estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions.
METHODS: All patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000 person-years were calculated.
RESULTS: Of 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).
CONCLUSIONS: The removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation.

Sokolov M, Toshev S, Todorov G, et al.
Per magna-ovarian metastases from primary locally advanced colorectal cancer--a review of the literature with a description of three clinical cases.
Khirurgiia (Sofiia). 2013; (3):39-47 [PubMed] Related Publications
Krukenberg tumor is defined as metastatic lesions of gastrointestinal cancers. Several specific immunohistochemical methods can identify the main focus of malignant neoplasm. Ovarian metastases from colorectal cancer are rarely seen phenomenon. The authors examine in detail the literature on this issue and describe three own clinical cases of metachronous ovarian meta lesions in women undergoing surgery for locally advanced colorectal cancer--two of these metastases are unilateral, while one--bilateral established in a short time interval despite the casuistic nature of the pathology. One of the patients died in the early postoperative period of co-morbid complications unrelated to the underlying disease, and the other two monitoring continues during the adjuvant. Krukenberg-metastases from colorectal cancer occur in the blood-vascular pattern in time without damage to the left or right ovary. Metachronous development and operative treatment of ovarian metastases is far better prognosis of the cases with and operated simultaneously established metastases in the ovaries.

Related: Colorectal (Bowel) Cancer

Wang H, Mu X, Zhou S, et al.
NEDD9 overexpression is associated with the progression of and an unfavorable prognosis in epithelial ovarian cancer.
Hum Pathol. 2014; 45(2):401-8 [PubMed] Related Publications
Neural precursor cell-expressed, developmentally down-regulated 9 (NEDD9), a scaffolding protein, has been identified as a prometastatic and poor prognostic gene in multiple malignant tumors. However, the potential role of the NEDD9 protein in epithelial ovarian cancer (EOC) remains unclear. In the present study, we investigated the expression of NEDD9 and the correlation between NEDD9 expression and prognosis in EOC. NEDD9 expression was detected in 129 archived EOC specimens by immunohistochemical staining and in 28 freshly frozen EOC specimens by Western blotting. The expression of NEDD9 was evaluated in ovarian cancer cell lines by Western blotting and immunofluorescence. The association between the expression of NEDD9 and prognosis was determined by survival analysis. Results suggested that NEDD9 was overexpressed in EOC specimens compared with noninvasive epithelial ovarian tumors and normal ovarian specimens. A high level of NEDD9 expression significantly correlated with advanced-stage tumors (International Federation of Gynecology and Obstetrics classes III-IV, P < .001), high-grade carcinoma (grades 2-3, P < .001), and suboptimal primary cytoreductive surgery (residual disease <1cm, P = .021). The expression level of NEDD9 varied in ovarian cancer cell lines. Multivariate analysis indicated that NEDD9 overexpression (P = .033), advanced stage (P < .001), and high-grade carcinoma (P = .01) were independent predictors of poor survival. In conclusion, NEDD9 is overexpressed and associated with an unfavorable prognosis in EOC. NEDD9 overexpression is an independent factor of poor prognosis and may serve as a potential biomarker in EOC.

Lairson DR, Parikh RC, Cormier JN, Du XL
Cost-utility analysis of platinum-based chemotherapy versus taxane and other regimens for ovarian cancer.
Value Health. 2014 Jan-Feb; 17(1):34-42 [PubMed] Related Publications
OBJECTIVES: Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or randomized control trials, but evidence integrating real-world survival, cost, and utility data is limited.
METHODS: A propensity score-matched cohort of 6856 elderly (≥65 years) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology, and End Results-Medicare data cohort were included. Treatment regimens (i.e., no chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum) were identified in the 6 months postdiagnosis. Patients were followed until death or end of study (December 2006). Effectiveness was measured in quality-adjusted life-years (QALYs), and total health care costs were measured by using a payer's perspective (2009 US dollars). Methodological and statistical uncertainties were accounted by including alternative scenarios (for utility values) and net monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were calculated, and stratified analyses were performed by tumor stages and age groups.
RESULTS: On comparing the platinum-based group versus no chemotherapy, we found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage disease, respectively, while other nonplatinum and platinum plus taxane groups were dominated (less effective and more costly). Similar results were found across alternative scenarios and age groups. For patients 85 years or older, platinum plus taxane, however, was not dominated by the platinum-based group, with an ICER of $133,892/QALY.
CONCLUSIONS: Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life, we found that treatment with platinum-based regimen was the most cost-effective treatment alternative.

Related: USA

Havrilesky LJ, Gierisch JM, Moorman PG, et al.
Oral contraceptive use for the primary prevention of ovarian cancer.
Evid Rep Technol Assess (Full Rep). 2013; (212):1-514 [PubMed] Related Publications
OBJECTIVE: To estimate the overall balance of harms and benefits from the potential use of oral contraceptives (OCs) for the primary prevention of ovarian cancer
DATA SOURCES: We searched PubMed®, Embase®, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for English-language studies published from January 1990 to June 2012 that evaluated the potential benefits (reduction in ovarian, colorectal, and endometrial cancers) and harms (increase in breast and cervical cancer, and vascular complications) of OC use.
REVIEW METHODS: Two investigators screened each abstract and full-text article for inclusion; the investigators abstracted data, and they performed quality ratings, applicability ratings, and evidence grading. Random-effects models were used to compute summary estimates of effects. A simulation model was used to estimate the effects of OC use on the overall balance of benefits and harms.
RESULTS: We reviewed 55 studies relevant to ovarian cancer outcomes, 66 relevant to other cancers, and 50 relevant to vascular events. Ovarian cancer incidence was significantly reduced in OC users (OR [odds ratio], 0.73; 95% CI [confidence interval], 0.66 to 0.81), with greater reductions seen with longer duration of use. Breast cancer incidence was slightly but significantly increased in OC users (OR, 1.08; 95% CI, 1.00 to 1.17), with a significant reduction in risk as time since last use increased. The risk of cervical cancer was significantly increased in women with persistent human papillomavirus infection who used OCs, but heterogeneity prevented a formal meta-analysis. Incidences of both colorectal cancer (OR, 0.86; 95% CI, 0.79 to 0.95) and endometrial cancer (OR, 0.57; 95% CI, 0.43 to 0.76) were significantly reduced by OC use. The risk of vascular events was increased in current OC users compared with nonusers, although the increase in myocardial infarction was not statistically significant. The overall strength of evidence for ovarian cancer prevention was moderate to low, primarily because of the lack of randomized trials and inconsistent reporting of important characteristics of use, such as duration. The simulation model predicted that the combined increase in risk of breast and cervical cancers and vascular events was likely to be equivalent to or greater than the decreased risk in ovarian cancer, although the harm/benefit ratio was much more favorable when protection against endometrial and colorectal cancers was added, resulting in net gains in life expectancy of approximately 1 month.
CONCLUSIONS: There is insufficient evidence to recommend for or against the use of OCs solely for the primary prevention of ovarian cancer. Although the net effects of the current patterns of OC use likely result in increased life expectancy when other noncontraceptive benefits are included, the harm/benefit ratio for ovarian cancer prevention alone is uncertain, particularly when the potential quality-of-life impact of breast cancer and vascular events are considered.

Deval B, Rousset P, Bigenwald C, et al.
Treatment of ovarian anaplastic ependymoma by an aromatase inhibitor.
Obstet Gynecol. 2014; 123(2 Pt 2 Suppl 2):488-91 [PubMed] Related Publications
BACKGROUND: Histopathologic diagnosis and treatment of ovarian anaplastic ependymoma are challenging.
CASE: A 61-year-old-woman presented with a 10-cm right adnexal tumor associated with peritoneal carcinomatosis extending to the right diaphragm and liver surface. After initial diagnosis of a papillary serous carcinoma, we performed extensive but nonoptimal cytoreductive surgery including hysterectomy with bilateral oophorectomy. Histology revealed some axially arranged cells with a prominent fibrillary cytoplasm, suggesting an ependymoma. Diagnosis was confirmed by immunophenotype showing strong positivity to glial fibrillary acidic protein. Given the strong tumoral expression of estrogen and progesterone receptors, an aromatase inhibitor was initiated. One year later, computed tomography scan showed stability of the residual peritoneal nodules.
CONCLUSION: Aromatase inhibitor treatment could be effective in cases of extraaxial ependymoma with prominent estrogen receptor expression.

Lentz SE, Tierney KE, Weaver FA, Roman LD
Abdominal aortic resection and Y-graft placement to achieve complete cytoreduction in stage IIIc ovarian carcinoma.
Obstet Gynecol. 2014; 123(2 Pt 2 Suppl 2):486-8 [PubMed] Related Publications
BACKGROUND: Major vascular resection with reconstruction in patients with gynecologic malignancy is rarely performed and infrequently reported.
CASE: A 40-year-old woman undergoing surgery for stage IIIc ovarian papillary serous adenocarcinoma was left with a 7-cm aortic metastasis not separable from the infrarenal abdominal aorta. An aortic resection with prosthetic graft placement was performed to achieve complete tumor resection. She remains disease-free in excess of 10 years with no evidence of graft complication.
CONCLUSION: Major vascular reconstructive procedures for the management of malignancy need not be precluded in properly selected circumstances.

Schickler RL, Hoffman MS, Plosker SM
Elevated human chorionic gonadotropin and hyperandrogenemia in a woman with Müllerian agenesis.
Obstet Gynecol. 2014; 123(2 Pt 2 Suppl 2):465-8 [PubMed] Related Publications
BACKGROUND: Müllerian agenesis is a congenital malformation characterized by absence of the uterus, cervix, and upper vagina. A positive home pregnancy test in a woman with Müllerian agenesis mandated evaluation for malignancy.
CASE: A woman with Müllerian agenesis presented with elevated levels of human chorionic gonadotropin (hCG), testosterone, and dehydroepiandrosterone sulfate. Pelvic magnetic resonance imaging (MRI), abdominal and pelvic computed tomography scan, chest computed tomography scan, brain MRI, and body positron emission tomography scan did not identify a malignancy. Human chorionic gonadotropin characterization revealed 74% hyperglycosylated and 1.6% free β-hCG, suggesting a trophoblast-containing tumor. Interventional ovarian venous sampling and repeat pelvic MRI suggested a right adnexal source. After laparoscopic removal of a stage 1C right ovarian dysgerminoma, hCG and testosterone returned to normal.
CONCLUSION: A dysgerminoma coincident with Müllerian agenesis expressed hCG before detection by MRI. Human chorionic gonadotropin molecular characterization, ovarian vein sampling, and repeat pelvic MRI led to successful treatment.

Verma J, Sulman EP, Jhingran A, et al.
Dosimetric predictors of duodenal toxicity after intensity modulated radiation therapy for treatment of the para-aortic nodes in gynecologic cancer.
Int J Radiat Oncol Biol Phys. 2014; 88(2):357-62 [PubMed] Related Publications
PURPOSE: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity.
METHODS AND MATERIALS: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scored according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity.
RESULTS: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm(3) were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity.
CONCLUSIONS: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm(3) may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints, consideration should be given to other treatment approaches such as resection or initial chemotherapy.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Cervical Cancer

Huq F, Yu JQ, Beale P, et al.
Combinations of platinums and selected phytochemicals as a means of overcoming resistance in ovarian cancer.
Anticancer Res. 2014; 34(1):541-5 [PubMed] Related Publications
Cancer sufferers are often found to use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In this study, we investigated synergism from the combination of platinum drugs and a number of tumour-active phytochemicals including curcumin, epigallocatechin-3-gallate, thymoquinone, genistein, resveratrol, betulinic acid and ursolic acid in three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), as a function of concentration and the sequence of administration. Both the dose-effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals exert concentration- and sequence-dependent synergism in the cell lines. Generally the degree of synergism is found to be greater in sequenced administration such as 0/2 h, 2/0 h, 0/4 h and 4/0 h than the bolus. The variation in the nature of the combined drug action from being highly synergistic to antagonistic with the change in sequence of administration clearly indicates that the action of one drug modulates that of the other (towards the induction or inhibition of apoptosis). We have also used sequenced combinations of platinum drugs and bortezomib (a proteasome inhibitor that prevents cisplatin-induced proteasomal degration of copper transporter CTR1) to enhance cellular platinum accumulation and the level of platinum-DNA binding especially in the resistant human ovarian tumour models. Proteomic studies to identify the key proteins associated with platinum resistance are ongoing. We have identified 59 proteins associated with platinum resistance in ovarian tumor models.

Related: Apoptosis

Stölting DP, Borrmann M, Koch M, et al.
How liposomal Cisplatin overcomes chemoresistance in ovarian tumour cells.
Anticancer Res. 2014; 34(1):525-30 [PubMed] Related Publications
The frequent development of cellular resistance to cisplatin in cancer patients is a serious limitation for clinical drug therapy. However, cisplatin resistance is incompletely understood. We have shown that cisplatin-resistant A2780 ovarian cancer cells (A2780cis) can efficiently be eliminated by liposomal cisplatin, which displayed similar cytotoxicity towards both A2780 and A2780cis cells. This may, at least in part, be related to a higher intracellular accumulation of the drug within the resistant cells after liposomal entry. However, the superior cytotoxicity of the liposomal drug was not reflected by DNA platination. This suggests a more complex mode of action of liposomal cisplatin, most likely affecting different signaling pathways. To gain insight into the resistance gene signature, a whole-genome gene expression analysis was performed for A2780cis cells, untreated or treated with half-minimal inhibitory concentration (IC50) of free and liposomal cisplatin. Strong differences in the functional networks affected by free and liposomal cisplatin became evident. p53 was identified as a key factor directing differences in the apoptotic processes. While free cisplatin induced the intrinsic pathway of apoptosis, liposomal cisplatin induced expression of genes of DNA damage pathways and of the extrinsic pathway of apoptosis. These predictions from gene expression data were confirmed at the protein and function level. This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal cisplatin as a promising strategy for the treatment of cisplatin-resistant ovarian carcinoma.

Related: Apoptosis Cisplatin

Engelmann BJ, Ryan JJ, Farrell NP
Antidepressants and platinum drugs.
Anticancer Res. 2014; 34(1):509-16 [PubMed] Related Publications
BACKGROUND/AIM: Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin.
MATERIALS AND METHODS: The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay.
RESULTS: The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin.
CONCLUSION: The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

Related: Apoptosis Carboplatin Cisplatin Oxaliplatin

Kubelac MP, Fetica B, Vlad IC, et al.
The role of inhibitor of DNA-binding 1 (ID-1) protein and angiogenesis in serous ovarian cancer.
Anticancer Res. 2014; 34(1):413-6 [PubMed] Related Publications
BACKGROUND: Overexpression of Inhibitor of DNA-binding 1 protein (ID-1) is correlated with poor prognosis in some malignancies and few studies have assessed its role in ovarian cancer. This led us to investigate its association with the microvessel density (MVD) in patients with ovarian cancer.
MATERIALS AND METHODS: Fifty-six patients with epithelial serous ovarian cancer were selected. The early-stage group consisted of 14 patients and the advanced-stage group comprised 42 patients. ID-1 expression and MVD were evaluated by immunohistochemistry. Results and
CONCLUSION: The histoscore for ID-1 and MVD were significantly higher in advanced-stage cancer (p<0.05). The MVD was significantly higher in the high ID-1 expression group compared to the low ID-1 expression group (p<0.001). The mean follow-up time was 52 months. The survival period in patients with high ID-1 expression was not significantly shorter than for those with low ID-1 expression (p=0.62). The role of ID-1 protein requires further investigation.

Related: Angiogenesis and Cancer

Muallem MZ, Braicu I, Nassir M, et al.
ERCC1 expression as a predictor of resistance to platinum-based chemotherapy in primary ovarian cancer.
Anticancer Res. 2014; 34(1):393-9 [PubMed] Related Publications
AIM: The purpose of the present study was to investigate the possible association between Excision repair cross-complementing group 1 (ERCC1) score and platinum resistance in first-line chemotherapy for ovarian cancer.
PATIENTS AND METHODS: ERCC1 Expression was determined using immunohisto-chemistry in 68 patients with platinum-responding tumor and 30 with platinum-resistant tumors. The primary end-point of this study was the association between the expression of ERCC1 protein with resistance to standard platinum-based chemotherapy in primary ovarian cancer.
RESULTS: In pairwise comparisons, the overall survival (OS) for patients with ovarian cancer, who were non-responders to platinum-based chemotherapy with low or intermediate H-score for ERCC1 was better than that of non-responders with high H-score for ERCC1 [median OS=21 (16.8-25.2 months) and 28 (14.6-41.4 months) vs. 15 months (6.2-23.8 months), p-value=0.048, and p-value=0.017, respectively].
CONCLUSION: There were no significant differences in the progression-free survival between those with low, intermediate and high H-score for ERCC1. There is no statistically significant relationship between ERCC1 score and response to platinum-based chemotherapy in patients with primary ovarian cancer.

Related: Carboplatin Cisplatin

Dunn GP, Cheung HW, Agarwalla PK, et al.
In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene.
Proc Natl Acad Sci U S A. 2014; 111(3):1102-7 [PubMed] Article available free on PMC after 21/07/2014 Related Publications
High-grade serous ovarian cancers are characterized by widespread recurrent copy number alterations. Although some regions of copy number change harbor known oncogenes and tumor suppressor genes, the genes targeted by the majority of amplified or deleted regions in ovarian cancer remain undefined. Here we systematically tested amplified genes for their ability to promote tumor formation using an in vivo multiplexed transformation assay. We identified the GRB2-associated binding protein 2 (GAB2) as a recurrently amplified gene that potently transforms immortalized ovarian and fallopian tube secretory epithelial cells. Cancer cell lines overexpressing GAB2 require GAB2 for survival and show evidence of phosphatidylinositol 3-kinase (PI3K) pathway activation, which was required for GAB2-induced transformation. Cell lines overexpressing GAB2 were as sensitive to PI3K inhibition as cell lines harboring mutant PIK3CA. Together, these observations nominate GAB2 as an ovarian cancer oncogene, identify an alternative mechanism to activate PI3K signaling, and underscore the importance of PI3K signaling in this cancer.

Related: Signal Transduction

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.

Vergote IB, Jimeno A, Joly F, et al.
Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study.
J Clin Oncol. 2014; 32(4):320-6 [PubMed] Related Publications
PURPOSE: This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.
PATIENTS AND METHODS: Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.
RESULTS: Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.
CONCLUSION: Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.

Related: Fallopian Tube Cancer FISH Signal Transduction EGFR Erlotinib (Tarceva)

Virzì S, Iusco D, Baratti D, et al.
Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases.
Tumori. 2013 Sep-Oct; 99(5):589-95 [PubMed] Related Publications
AIMS AND BACKGROUND: The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases.
METHODS: Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed.
RESULTS: Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%.
CONCLUSIONS: Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Related: Cisplatin Colorectal (Bowel) Cancer Mitomycin

Zhang Z, Zhou B, Wu Y, et al.
Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population.
Immunogenetics. 2014; 66(2):85-92 [PubMed] Related Publications
This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan-Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] = 1.333, 95% confidence interval [CI] = 1.133-1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR = 1.766, 95% CI = 1.258-2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P < 0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.

Pu X, Ma C, Yin G, et al.
Cell adhesion and invasion inhibitory effect of an ovarian cancer targeting peptide selected via phage display in vivo.
Biochem Biophys Res Commun. 2014; 443(3):858-63 [PubMed] Related Publications
Organ-specific metastasis is of great importance since most of the cancer deaths are caused by spread of the primary cancer to distant sites. Therefore, targeted anti-metastases therapies are needed to prevent cancer cells from metastasizing to different organs. The phage clone pc3-1 displaying peptide WSGPGVWGASVK selected by phage display had been identified which have high binding efficiency and remarkable cell specificity to SK-OV-3 cells. In the present work, the effects of selected cell-binding phage and cognate peptide on the cell adhesion and invasion of targeted cells were investigated. Results showed that the adhesive ability of SK-OV-3 to extracellular matrix was inhibited by pc3-1 and peptide WSGPGVWGASVK, and pc3-1 blocked SK-OV-3 cells attachment more effective than the cognate peptide. The peptide WSGPGVWGASVK suppressed the cell number of SK-OV-3 that attached to HUVECs monolayer up to 24% and could block the spreading of the attaching cells. Forthermore, the cognate peptide could inhibit the invasion of SK-OV-3 significantly. The number of invaded SK-OV-3 cells and invaded SK-OV-3-activated HUVECs pretreated with peptide WSGPGVWGASVK was decreased by 24.3% and 36.6%, respectively. All these results suggested that peptide WSGPGVWGASVK might possess anti-metastasis against SK-OV-3 cells.

Burandt E, Young RH
Pregnancy luteoma: a study of 20 cases on the occasion of the 50th anniversary of its description by Dr. William H. Sternberg, with an emphasis on the common presence of follicle-like spaces and their diagnostic implications.
Am J Surg Pathol. 2014; 38(2):239-44 [PubMed] Related Publications
Twenty cases of the distinctive tumor-like lesion of the ovary, pregnancy luteoma, are described, with emphasis on pathologic features. The masses occurred in patients from 15 to 44 years of age and were typically incidental findings at or near term. Four patients experienced androgenic manifestations. The luteoma was documented to be bilateral in only 4 cases, but the opposite ovary was usually not evaluated pathologically. They ranged up to 15 cm. Sectioning typically showed multiple nodules or a single discrete mass with a multinodular sectioned surface and a soft bulging appearance. Most lesions were brown, but a few were black or yellow at least focally. Foci of hemorrhage were common. The most common microscopic appearance was a diffuse growth, but it was punctuated in about three quarters of the cases by follicle-like spaces often containing colloid-like secretion. These spaces are much more characteristic of the pregnancy luteoma than of the lesion most often in the differential diagnosis, a steroid cell tumor, and accordingly may be of diagnostic aid. However, they may cause confusion, as follicle-like spaces are a nonspecific feature of a number of neoplasms involving the ovary and potentially in the differential diagnosis. Awareness of the clinical background and frequency of finding follicle-like spaces in pregnancy luteoma are important diagnostically, and standard immunohistochemical stains will aid should they be warranted.

Related: Breast cancer in pregnancy

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