Risk Of Ovarian Malignancy Research Articles

Is It Possible to Prevent Nontherapeutic Laparotomies in Breast Cancer Patients With Isolated Adnexal Masses?

Introduction: The risk of ovarian malignancy is increasing in patients with a history of breast cancer. Thus, well-defined predictors of ovarian malignancy should be identified to determine surgical or conservative management of adnexal masses in women with breast cancer. This study aimed to clarify the predictors of malignant ovarian tumors in patients with breast cancer with an isolated adnexal mass. Methods: Breast cancer patients diagnosed with an adnexal mass who underwent surgery between 2010 and 2021 at a tertiary cancer center were included in the study. Patients with suspected extra ovarian metastases were excluded. Results: A total of 40 breast cancer patients who underwent surgery for ovarian masses were identified. 23 (57.5%) women had benign ovarian tumors and 17 (42.5%) had malignant ovarian tumors. Among the malignant ovarian tumors, there were three (17.6%) metastatic breast cancers in the ovary and 14 (82.4%) primary ovarian cancers. In univariate analyses, the risk of malignant ovarian tumors increased in women with age >52years (P = .012), postmenopausal status (P = .023), CA 125 ≥ 35IU/ml (P = .001), CA 15-3 ≥ 32IU/ml (P = .002), and complex ovarian masses (P < .001). Ovarian malignancies were observed in 82.4% of patients who had complex ovarian masses. Conclusion: Ovarian malignancies were diagnosed in 82.4% of the breast cancers who had complex ovarian mass on USG examination. Therefore, surgery is recommended in women with complex ovarian masses. Postmenopausal status, age >52years, CA 125 ≥ 35IU/ml, and CA 15-3 ≥ 32 were other risk factors for ovarian malignancy.

Association between Rheumatoid Arthritis Disease Activity and Risk of Ovarian Malignancy in Middle-Aged and Elderly Women.

Objective To investigate the risk of ovarian malignancy in middle-aged and elderly women with rheumatoid arthritis (RA) and its correlation with disease activity. Methods 219 middle-aged and elderly (age ≥ 40) female RA patients who were treated at the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from August 2019 to September 2020 were selected. Their general information such as age and medical history was collected. RA disease activity-related indicators include rheumatoid factor (RF), anticyclic citrullinated peptide antibody (ACPA), ESR, CRP, and ovarian malignancy risk-related indicators including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected. According to Risk of Ovarian Malignancy Algorithm (ROMA), they were divided into a low-risk group (ROMA-low, premenopausal: ROMA ≤ 11.4%, postmenopausal: ROMA ≤ 29.9%) and a high-risk group (ROMA-high, premenopausal: ROMA > 11.4%, postmenopausal: ROMA > 29.9%) for ovarian malignancy. Meanwhile, according to the DAS28-ESR, they were divided into the general disease activity group (DAS28-ESR ≤ 5.1) and the high disease activity group (DAS28-ESR > 5.1). SPSS 25.0 software was used to compare the differences among groups and to analyze the correlation between ovarian malignancy risk and RA disease activity. Results Compared with the ROMA-low group, the levels of RF, ACCP, CDAI, SDAI, DAS28-ESR, and DAS28-CRP in the ROMA-high group were significantly increased (P < 0.05). HE4 and ROMA in the high disease activity group were significantly higher than general disease activity group (P < 0.05). Spearman correlation analysis showed that age (r = 0.472), RF (r = 0.221), ACPA (r = 0.156), CDAI (r = 0.226), SDAI (r = 0.221), DAS28-ESR (r = 0.254), DAS28-CRP (r = 0.208), medications (r = 0.189), and CA199 (r = 0.250) were correlated with ROMA (P < 0.05). Multivariate regression analysis showed that ESR (OR = 1.11), SDAI (OR = 1.02), DAS28-ESR (OR = 1.33), DAS28-CRP (OR = 1.26), and CA199 (OR = 1.03) were independent risk factors for high risk of ovarian malignancy (P < 0.05). Subgroup analysis showed that CA199 is an effect modification factor for DAS28-ESR (P < 0.05). Conclusion The risk of ovarian malignancy is significantly increased in middle-aged and elderly women with high disease activity with rheumatoid arthritis. In clinical, full attention should be paid to the risk of ovarian malignancy in this population. Screening in time, especially in patients with increased DAS28-ESR and CA199 at the same time, is needed.

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

Epithelial ovarian cancer has become the most frequent cause of deaths among gynecologic malignancies. Our study elucidates the diagnostic performance of Risk of Ovarian Malignancy Algorithm (ROMA), Human epididymis secretory protein 4 (HE4) and cancer antigen (CA125). To compare the diagnostic accuracy of ROMA, HE-4 and CA125 in the early diagnosis and screening of Epithelial Ovarian Cancer. Literature search in electronic databases such as Medicine: MEDLINE (through PUBMED interface), EMBASE, Google Scholar, Science Direct and Cochrane library from January 2011 to August 2020. Studies that evaluated the diagnostic measures of ROMA, HE4 and CA125 by using Chemilumincence immunoassay or electrochemiluminescence immunoassay (CLIA or ECLIA) as index tests. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We included 32 studies in our meta-analysis. We calculated AUC by SROC, pooled estimated like sensitivity, specificity, likelihood ratio, diagnostic odds ratio (DOR), Tau square, Cochran Q through random effect analysis and meta-regression. Data was retrieved from 32 studies. The number of studies included for HE4, CA125 and ROMA tests was 25, 26 and 22 respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068 respectively for the markers or algorithm. The pooled estimates of the markers or algorithm were sensitivity: ROMA (postmenopausal) (0.88, 95% CI 0.86–0.89) > ROMA (premenopausal) 0.80, 95% CI 0.78–0.83 > CA-125(0.84, 95% CI 0.82–0.85) > HE4 (0.73, 95% CI 0.71–0.75) specificity: HE4 (0.90, 95% CI 0.89–0.91) > ROMA (postmenopausal) (0.83, 95% CI 0.81–0.84) > ROMA (premenopausal) (0.80, 95% CI 0.79–0.82) > CA125 (0.73, 95%CI 0.72–0.74), Diagnostic odd’s ratio ROMA (postmenopausal) 44.04, 95% CI 31.27–62.03, ROMA (premenopausal)-18.93, 95% CI 13.04–27.48, CA-125-13.44, 95% CI 9.97–18.13, HE4-41.03, 95% CI 27.96–60.21 AUC(SE): ROMA (postmenopausal) 0.94(0.01), ROMA (premenopausal)-0.88(0.01), HE4 0.91(0.01), CA125-0.86(0.02) through bivariate random effects model considering the heterogeneity. Our study found ROMA as the best marker to differentiate EOC from benign ovarian masses with greater diagnostic accuracy as compared to HE4 and CA125 in postmenopausal women. In premenopausal women, HE4 is a promising predictor of Epithelial ovarian cancer; however, its utilisation requires further exploration. Our study elucidates the diagnostic performance of ROMA, HE4 and CA125 in EOC. ROMA is a promising diagnostic marker of Epithelial ovarian cancers in postmenopausal women, while HE4 is the best diagnostic predictor of EOC in the premenopausal group. Our study had only EOC patients as cases and those with benign ovarian masses as controls. Further, we considered the studies estimated using the markers by the same index test: CLIA or ECLIA. The good number of studies with strict inclusion criteria reduced bias because of the pooling of studies with different analytical methods, especially for HE4. We did not consider the studies published in foreign languages. Since a few studies were available for HE4 and CA125 in the premenopausal and postmenopausal group separately, data were inadequate for sub-group analysis. Further, we did not assess these markers' diagnostic efficiency stratified by the stage and type of tumour due to insufficient studies.

Стратификация рисков злокачественности образований яичников. Интеграция МРТ в систему O-RADS

Стратификация рисков злокачественности образований яичников. Интеграция МРТ в систему O-RADS

Rare Case of Metastatic Ovarian Clear Cell Carcinoma With an In Vitro Fertilization Pregnancy

Abstract The risk of ovarian malignancy is rare in pregnancy with a reported incidence of approximately 1 in 50,000. Ovarian clear cell carcinoma (OCCC) accounts for 5% to 10% of all ovarian carcinomas with mean age of 50 to 55 years and is often associated with endometriosis. We present a case of 38-year-old G2P1 Asian female with an in vitro fertilization pregnancy and history of endometriosis who presented with the right adnexal mass. The transvaginal ultrasound performed during the early pregnancy was suggestive of endometrioma or desmoid tumor. At 32 weeks, the patient presented to the emergency department with preeclampsia and severe headache. An emergency cesarean section was performed due to worsening of the patient’s condition. An ovarian mass arising from the right ovary and with a friable and hemorrhagic internal surface was excised, which weighed 63 g and measured 14.0 × 10.5 × 3.0 cm. Its external surface was smooth, hemorrhagic, but without any excrescences. The serial sectioning revealed multiple cystic lesions filled with necrotic material overall occupying 80% of the mass. Microscopically, the viable ovarian tissue demonstrated tubulocystic/papillary architecture lined by hyperchromatic hobnail cells along with focal areas of solid sheets of tumor cells displaying clear cytoplasm. Immunohistochemical stains for Wilm’s tumor 1 and p53 were negative while positive for PAX8. These findings were indicative of OCCC without overexpression of wild-type p53. The PET scan performed few weeks after delivery showed widespread metastasis. We present a unique case of metastatic OCCC removed at the time of cesarean section in the late-preterm period. Our case not only emphasizes the need for definitive treatment option for endometriosis but also a close imaging surveillance of all masses diagnosed during pregnancy in women with risk factors such as endometriosis and Asian ethnicity. Furthermore, our study advocates the need for possible guidelines for management of such rare cases.

70. PREIMPLANTATION GENETIC TESTING FOR YQH-AUTOSOME TRANSLOCATION CARRIERS: ANALYSIS OF GAMETE SEGREGATION

Introduction Y-autosome translocations occur in approximately 1:2000 in population and represent special group of reciprocal exchanges. Due to a balanced nature they do not influence on phenotype in general. However, Y-autosome translocation can dislocate sex bivalent formation and chromosome synapsis in the first meiotic division prophase that led to gamete aneuploidy or pachytene arrest. More often Y-derived DNA, predominantly Yq12 band, is translocated onto the short arm of acrocentric chromosomes, mainly chromosomes 15 and 22 due to a strong correlation in their satellite DNA sequences. In women inheritance of such derivative acrocentric chromosomes could be associated with the risk of ovarian malignancy, but the particular mechanism of this pathological effect is not entirely clear since the Yq12 band consists of tandemly organized satellite DNA sequences. It can be associated with the transcription of satellite DNAwhich occurs during carcinogenesis. Material & methods Two families with Yq12/15p and one – with Yq12/22p translocations were analyzed during IVF cycle with PGT in International Centre for Reproductive Medicine. The mean age of men and women was 36±2.8 and 34.25±1.4 years respectively. Karyotyping analysis was performed using GTG banding technique on metaphase chromosomes from peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) was used to clarify the breakpoint on chromosomes and confirm the chromosomes-specificity of the probes. Additionally, seven chromosomes (13, 14, 15 or 22, 16, 18, 21, X), which are not involved in rearrangement, were analyzed. Results FISH with chromosome specific probes was performed on blastomere from cleavage-stage embryo. A total of 42 blastomeres were analyzed. In 43% of the blastomeres «adjacent-1» segregationwith derivate autosome and X or Y chromosomes was revealed. Segregation 3:1 was observed in 10% of the cells, with no predominant inheritance of the derivative autosome. In 21% of cells the type of chromosome segregation could not be determined due to mosaicismor polyploidy. 45% of the cells were aneuploid for autosomes, which are not involved in the translocation, which may be connected with interchromosomal effect. Conclusions Carriers of Yq12/15p or Yq12/22p translocations have a predominant inheritance of the derivative autosome, which can be associated with the disruption ofsex bivalent segregation. This research was supported by Russian Foundation for Basic Research (grant # 18-34-00279 ).

Risk of Ovarian Malignancy in Patients Undergoing Radical Cystectomy for Bladder Cancer

ObjectiveTo determine whether there is an increased risk of ovarian cancer in women undergoing radical cystectomy (RC) for bladder cancer using a large population-based data source. Current American Urologic Association guidelines suggest removal of ovaries during RC in women with bladder cancer, presumably to mitigate the risk ovarian cancer. However, recent data have demonstrated an increased risk of all-cause mortality, cardiovascular disease, osteoporosis, cognitive impairment, and diminished sexual function in some populations of women after oophorectomy. MethodsWe queried the surveillance, epidemiology and end results (SEER) database for all women with a diagnosis of primary bladder cancer who underwent RC between 1998 and 2010. Patients with concurrent or subsequent primary ovarian cancer were then identified using the SEER multiple primaries dataset. Multiple primary standardized incidence ratio was calculated as an estimate of the relative risk of a concurrent or subsequent ovarian malignancy using SEER*Stat software. ResultsA total of 1851 women met inclusion criteria for analysis. Of this population, 221 (11.9%) women developed a subsequent nonbladder malignancy, of which 2 (0.11%) women developed subsequent ovarian cancer during the observation period. Multiple primary standardized incidence ratio for development of an ovarian malignancy was 2/4 (0.50). ConclusionThe risk of concurrent or subsequent ovarian malignancy in women undergoing RC for bladder cancer is very low. Therefore, oophorectomy at the time of RC may be obviated in order to mitigate the undue risk of cardiovascular disease, osteoporosis, cognitive impairment, and diminished sexual function.

Risk of Ovarian Malignancy in Patients Undergoing Surgery for an Adnexal Mass at a High-Volume Cancer Center [36A

INTRODUCTION: To characterize a cohort of patients presenting to a high-volume cancer center with an adnexal mass (AM), reporting pathologic outcomes and risk of malignancy. METHODS: All new visits to the gynecology service were prospectively screened from July 1, 2015-5/31/2017. Patients with ovarian complaints were categorized prospectively and followed through treatment. AM was defined as a pelvic mass suspected to originate from the adnexa without apparent metastatic disease based on available clinical and radiographic studies. Clinicopathologic data were collected and analyzed. RESULTS: 7690 new visits were screened and 2964 patients with an ovarian complaint were categorized: AM 35%, suspected advanced ovarian cancer (ovca) 28%, recurrent ovca 13%, hereditary ovca syndrome 14%, endocrine ablation 8%, other 2%. Of the 1046 with AM, 2% had evidence of metastatic disease on preoperative imaging, 40% were recommended observation, and 58% were managed surgically. For the 607 managed surgically, final pathology showed: benign 74%, non-ovarian malignancy 12%, ovca 8%, borderline tumor 5%, serous tubal intraepithelial carcinoma &gt;1%, no pathology available &gt;1%. Of the 51 patients diagnosed with ovca, median age was 57(27-79 years), median CA125 67 U/ml(9-353 U/ml), and median preoperative AM size was 9.8cm(2.6-21.4cm). Final histologic diagnosis was: epithelial ovca 40(78%), sex cord stromal tumor 5(9.8%), germ cell tumor 1(1.9%), other 5(9.8%). The most common epithelial histology was high grade serous 18(45%). CONCLUSION: In patients who underwent surgery for AM with no radiologic evidence of metastatic disease at a high-volume cancer center, risk of ovca was 8% with the majority of patients having benign disease.

Role of Biomarkers in Screening and Diagnosis of Ovarian Cancer

The overall mortality of ovarian cancer exceeds that of other gynecologic cancers owing to lack of disease-specific symptoms. Three quarters of patients with ovarian cancer are diagnosed after the disease has progressed to advanced stage. Thus, improvement of an effective screening tool could result in better prognosis and survival. To date, cancer antigen 125 (CA-125) is the most commonly used serum biomarker for detecting ovarian cancer. However, the test has low sensitivity for the disease detection (50-62% for early stage epithelial ovarian cancer) and limited specificity. Therefore, CA-125 as a single test is not recommended for ovarian cancer screening in asymptomatic women. CA-125 in combination with human epididymis protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA) is becoming widely used in clinical practice for the evaluation of adnexal masses. Clinical examination, transvaginal ultrasonography (TVS) and serum biomarkers (ROMA) more effectively classify the patients into low and high risk of ovarian malignancy. The classification allows to direct the patients to appropriate management by gynecologic oncologists, and thus the survival rate could be improved. Role of serum biomarkers as the screening and diagnosis of ovarian cancer is described in this review.

Adnexal Torsion in Postmenopausal Women: Clinical Presentation and Risk of Ovarian Malignancy

Study ObjectiveTo investigate the clinical presentation, operative outcome, and incidence of malignancy in postmenopausal women who were diagnosed with adnexal torsion. DesignRetrospective cohort study (Canadian Task Force classification II-2). SettingTertiary university-affiliated hospital. PatientsPostmenopausal women diagnosed with adnexal torsion between 1995 and 2014 (study group) were reviewed and compared with 220 premenopausal patients diagnosed with adnexal torsion during the same time period. InterventionDemographic data, clinical signs and symptoms, and intra- and postoperative characteristics were compared between the 2 groups. Measurements and Main ResultsDuring the study period 44 postmenopausal women were diagnosed with adnexal torsion. Continuous dull pain was the most common presenting symptom in the postmenopausal group (57%), whereas acute-onset sharp pain was the predominant symptom in the premenopausal group (86%). The time interval from admission to surgery was significantly longer in the postmenopausal group (24 vs 6 hours, p < .001). Laparoscopic surgery was performed in 84.5% of the cases in the premenopausal group, whereas it was carried out in only 50% of cases in the postmenopausal group (p < .001). Four women in the postmenopausal group were diagnosed with malignancy, whereas only 1 case of malignancy was found in the premenopausal group (9% vs .4%, respectively; p = .003). ConclusionsAdnexal torsion in postmenopausal women is an uncommon event with a unique presentation. Because ovarian malignancy is not an uncommon finding in this group of patients, preparation for more extensive surgery should be contemplated.

Derivation of a second generation multivariate index assay to improve specificity in pre-surgical evaluation of adnexal masses for risk of ovarian malignancy.

5561 Background: The FDA cleared in vitro diagnostic multivariate index assay OVA1, with its intended utility to assist in referral of high risk patients to gynecologic oncologists, was by design t...

A panel of biomarkers to improve specificity in presurgical assessment of adnexal masses for risk of ovarian malignancy.

5573 Background: OVA1 is a panel of biomarkers cleared by FDA currently in clinical use for pre-surgical assessment of adnexal masses for risk of ovarian malignancy. To further improve the specificity of OVA1, we evaluated biomarkers using a designed set of clinical samples enriched with OVA1 false positive benign patients and selected insulin-like growth factor binding protein 2 (IGFBP2), interleukin 6 (IL6), and follicle-stimulating hormone (FSH) to be further evaluated along with the original five biomarkers of OVA1 on a prospectively collected clinical sample set. The inclusion of FSH was to eliminate the need for menopause-specific cutoffs. Methods: Consecutive patients with a documented pelvic mass planned for surgical intervention were prospectively enrolled at 27 sites. Exclusion criteria included a diagnosis of malignancy in the previous 5 years or initial enrollment by a gynecologic oncologist. At the time of analysis, 384 subjects had all biomarker values. Among them 69 were ovarian cancer cases (13 LMPs, 27 stages 1/2, 19 serous, 11 endometrioid , 5 mucinous, and 4 clear cell). Biomarkers were tested by ELISA and reported as continuous values. Using a subset of the samples, the biomarkers were first selected for inclusion in a final panel based on contributions in multivariate models estimated by bootstrap. The selected biomarkers were further assessed for ability to improve specificity of risk stratification at a fixed sensitivity over that of OVA1 using the full data set. This was done by cross-validation of multivariate models with 50/50 split between training and testing. Results: The final panel of biomarkers consisted of CA125II, prealbumin, IGFBP2, IL6, and FSH. At a fixed sensitivity of 90%, the mean and median specificity of models using the new panel in testing were 78.2% (95% CI: 76.7 – 79.8%), and 80.6%, respectively. The mean and median absolute improvements over that of OVA1 were 18.6% (95% CI: 16.4% – 20.9%) and 20.3%, respectively. Conclusions: The new panel demonstrated the potential to significantly improve specificity over that of the first-generation OVA1 algorithm, while maintaining a high sensitivity in pre-surgical assessment of adnexal masses for risk of malignancy.

Adnexal masses in women with breast cancer

Adnexal masses detected in breast cancer survivors are of particular concern because of the increased risk of ovarian malignancy. This study was performed to analyse adnexal masses among women with breast cancer with regard to variables predictive of malignancy. The study included women with breast cancer who had undergone surgery for an adnexal mass between 2002 and 2010 at Hacettepe University Hospital. A total of 45 consecutive women with a mean age of 47.3years (range 25-76) were analysed retrospectively. Of 45 cases reviewed, benign ovarian pathology was found in 35 cases (77.8%) and malignant ovarian neoplasms were found in 10 cases (22.2%). A simple ovarian cyst was observed in 25 cases (71.4%) as the most common type of benign pathology. Of the 10 cases with malignancy, 5 (50%) had primary ovarian carcinoma, while the remaining five women had breast carcinoma metastases to the ovary. Complex mass at ultrasonography, increased CA 125 level and oestrogen receptor-negative tumour were found to be the significant predictors of ovarian malignancy. Although an adnexal mass in a woman with breast cancer is most commonly a benign ovarian cyst, the overall risk of ovarian malignancy is increased with breast cancer. An adnexal mass with complex architecture detected by ultrasonography and high CA 125 level were the strongest risk factors associated with increased risk of malignancy.

FSH stimulates expression of the embryonic gene HMGA2 by downregulating let-7 in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas

FSH may increase the risk of ovarian malignancy and play a key role in ovarian carcinogenesis, although the mechanism(s) are undefined. HMGA2 overexpression has been observed to be an early genetic event in tumorigenesis. The present study was designed to investigate the effect of FSH on let-7, HMGA2 and p53 expression in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas (HGSCs). A primary human Fallopian tube (FT) fimbrial epithelium ex vivo culture system of low-grade serous carcinomas (LGSCs) and HGSCs was established. The levels of HMGA2, let-7, p53 and FSHR were evaluated by western blotting and reverse transcription (RT)-PCR. Treatment with FSH significantly increased HMGA2 expression in a time-dependent manner and the let-7 expression levels decreased gradually over time in the normal fimbrial epithelial cells of HGSCs. However, we did not observe similar results in LGSCs. In addition, knockdown of let-7 suppressed HMGA2 expression. p53 was not detected in the normal fimbrial epithelial cells before or after FSH administration. Our results indicate that FSH increases the expression of HMGA2 by downregulating the expression of let-7 in normal fimbrial epithelial cells of HGSCs, but no occurrence of p53 mutation. The susceptibility of fimbria to FSH in HGSCs compared with those in LGSCs is different.

Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort.

BACKGROUNDLong-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown.METHODSWe identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997–1999, data on reproductive risk factors were obtained from 65% of women and data on subfertility (treatment) were obtained from the medical records. The incidence of ovarian malignancies (including borderline ovarian tumours) through 2007 was assessed through linkage with disease registries. The risk of ovarian malignancies in the IVF group was compared with risks in the general population and the subfertile comparison group.RESULTSAfter a median follow-up of 14.7 years, the risk of borderline ovarian tumours was increased in the IVF group compared with the general population [standardized incidence ratio (SIR) = 1.76; 95% confidence interval (CI) = 1.16–2.56]. The overall SIR for invasive ovarian cancer was not significantly elevated, but increased with longer follow-up after first IVF (P = 0.02); the SIR was 3.54 (95% CI = 1.62–6.72) after 15 years. The risks of borderline ovarian tumours and of all ovarian malignancies combined in the IVF group were significantly increased compared with risks in the subfertile comparison group (hazard ratios = 4.23; 95% CI = 1.25–14.33 and 2.14; 95% CI = 1.07–4.25, respectively, adjusted for age, parity and subfertility cause).CONCLUSIONSOvarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. More large cohort studies are needed to confirm these findings and to examine the effect of IVF treatment characteristics.

Abstract 3666: Follicle-stimulating hormone inhibits apoptosis and autophagy in ovarian cancer cells by activating survivin and Rab25

Abstract Follicle-stimulating hormone (FSH) has been demonstrated to increase the risk of ovarian malignancy, but the mechanisms remains unclear. Our previous results showed that FSH increases the expression of VEGF through activation of survivin, which is mediated by the activation of the PI3K/AKT signaling pathway. We reported, herein, that FSH promoted ovarian cancer cells proliferation and prevented apoptosis in vitro and in vivo. FSH up-regulated the expression of survivin and down-regulated the expression of programmed cell death 6 (PDCD6) and death receptor 5 (DR5), two molecules required for apoptosis induction. Further, we have defined that the decreased expression of DR5, but not PDCD6, was mediated by survivin. We have established animal xenografts tissue arrays, the tumors from the groups with FSH treatment had higher expression of survivin and lower expression of DR5 comparing with the tumors from untreated groups, further confirming the interaction of FSH-survivin-DR5. In addition, we have demonstrated that FSH does not only inhibit apoptosis, but also inhibit autophagy. FSH inhibits autophagy by activating mTOR pathway in ovarian cancer cells under different stress conditions, including serum starvation. By Reverse Phase Protein Arrays (RPPA) analysis and western blot confirmation, we found that FSH stimulation increases the level of Rab25 in multiple ovarian cancer cells in a dose dependent manner. Rab25, a small GTPase, is found to be associated with the progression of ovarian tumor. Rab25, belongs to Rab11 supfamily, was shown to involve in endosomal recycling. To study the role of FSH-Rab25 interaction in regulating autophagy, we knocked down Rab25 expression in ES-2, Hey and SKOv3 ovarian cancer cell lines by siRNA, and examined the effects of FSH on autophagy. Rab25 knockdown increased the starvation induced autophagy through the inhibition of pAkt, while FSH administration could partly reverse the effects of Rab25 knockdown, due to the increase of Rab25 expression stimulated by FSH. Our findings indicated that Rab25 is one of the molecules regulated by FSH in ovarian cancer cells that has a novel role as a regulator in autophagy. Taken together, we have demonstrated that FSH promotes ovarian cancer development through regulating expression of survivin, Rab25, PDCD6 and DR5, which in turn regulates cell proliferation, apoptosis as well as autophagy. Further understanding the molecular mechanisms of FSH in the process of ovarian carcinogenesis and development will ultimately help developing an effective cancer prevention method, and find a novel targeted therapy for ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3666.

Patients' preferences in mode of surgery of an adnexal mass

Objective. We assessed the preferences of women with an adnexal mass for the mode of surgery.Methods. A structured interview was designed in which women, scheduled for surgery for an adnexal mass, were confronted with fictive scenarios of the different approaches. Women were asked at what probability of a false negative test result of frozen section diagnosis they would prefer frozen section diagnosis over primary radical surgery. Furthermore, the women were asked at what probability of ovarian malignancy they would prefer laparoscopy over laparotomy.Results. We interviewed 43 women. When the probability of frozen section diagnosis being false negative was set at 90%, 97% of the women preferred primary radical surgery. The mean threshold at which women switched their preference from primary radical surgery to frozen section diagnosis was at a risk of 49% on a false negative test result of frozen section diagnosis. In the choice between laparoscopy over laparotomy, the mean threshold at which the women switched their preference from laparoscopy to laparotomy was at a risk of 55% on ovarian malignancy.Conclusion. Women scheduled for surgery of an adnexal mass at low risk of ovarian malignancy, prefer frozen section diagnosis over primary radical surgery and prefer laparoscopy over laparotomy.

Calcitonin gene polymorphismCALCA-624 (T/C) and ovarian cancer

In a previous analysis, we reported an inverse association of dietary calcium intake with the risk of ovarian cancer (Goodman et al. 2002. Am J Epidemiol 156:148-57). The CALCA gene codes for calcitonin, an important regulator of bone calcium metabolism. Data from a population-based case-control study conducted in Hawaii were used to examine the hypothesis that a T --> C transition 624 base pairs upstream (-624) of the translation initiation codon of the CALCA gene influences the risk of ovarian malignancy. A structured interview was conducted for 182 histologically confirmed ovarian cancer cases and 219 controls. Blood specimens were collected from the subjects at their homes. A significant negative trend (P for trend: 0.02) in the odds ratios (ORs) was found with increasing intake of calcium. Women with any CALCA C allele were at nonsignificantly higher risk of ovarian cancer (OR: 1.5, 95% CI: 0.9-2.3) compared to women with the TT genotype and the risk increased with the number of C alleles (P for trend: 0.05). When further analyzed within ethnic subgroups, a significant positive association was found among Japanese for CALCA CT (OR: 2.3, 95% CI: 1.0-5.3) and CALCA CC (OR: 7.2, 95% CI: 1.1-46.0) compared with Japanese women who were homozygous for the T allele. The trend in risk associated with the C allele was most significant among women who had used oral contraceptives (P for trend: 0.05), had been pregnant (P for trend: 0.04), and had nonmucinous histological types of ovarian cancer (P for trend: 0.02). However, the association of ovarian cancer risk with the CALCA genotype was not significantly modified by any of the dietary, nondietary, or clinical variables included in this study. These preliminary data suggest a strong positive association of the CALCA C allele with the risk of ovarian cancer among some subgroups.

Ovulation induction and ovarian malignancy.

Many couples faced with infertility are treated with ovulation inducing medicines. Recently, concerns have been raised about the possible risk of ovarian malignancy after such ovarian stimulation. Theories of pathogenesis for ovarian cancer include incessant ovulation, elevated pituitary gonadotropins, genetic predisposition, and chemical carcinogens. Protective factors include suppression of ovulation, pregnancy, and castration. Low numbers of exposed women who develop ovarian cancer make this a difficult research subject. Research to date demonstrates conflicting results, with some investigators reporting an increased risk of ovarian cancer with fertility drugs, whereas others do not. The likely magnitude of risk, if one believes a risk exists, may be two to three times that of the general population which is at most 4-5% in a woman's lifetime. The present uncertainty makes it challenging to apply this to today's practice of medicine. With continued efforts worldwide, we hope an understanding of this will be forthcoming.

Methylxanthine consumption and the risk of ovarian malignancy

Between 1970 and 1988, reports were published about two ecological studies, six case-control studies and one cohort study that evaluated the relationship between methylxanthine consumption and the risk of ovarian cancer. Because of the limitations of ecological studies, no inferences are based on them. All of the case-control studies recruited hospital controls. Nevertheless, four of the six had risk ratios of 1.5 or less. The one cohort study, which showed no relationship between coffee drinking and ovarian cancer, has low power. From these studies, it appears that coffee and tea consumption do not increase the risk of ovarian cancer.