Association of hysterectomy and invasive epithelial ovarian and tubal cancer: A cohort study within UKCTOCS

Objective: To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer. Design: Prospective cohort study. Setting: 13 NHS Trusts in England, Wales and Northern Ireland. Population: 202,506 postmenopausal women recruited between 2001-2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014. Methods: Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow-up or 31 December 2014. Cox proportional hazards regression models were used to assess the association. Main outcome measures: Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review. Results: Hysterectomy with conservation of one or both adnexa was reported in 41,912 (20.7%; 41,912/202,506) women. Median follow up was 11.1years (IQR 9.96-12.04), totalling >2.17million women-years. Among women who had undergone hysterectomy, 0.55% (231/41912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (RR=0.98, 95%CI 0.85-1.13, p=0.765). Conclusions: This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. This data is important both for clinical counselling and for refining risk prediction models.

Identification of signal transduction pathway activity with potential clinical target in high-grade serous ovarian and tubal carcinoma.

e17541 Background: High-grade serous carcinoma (HGSC) is the most common subtype of epithelial ovarian and tubal cancer. It has a high mortality rate, even after successful first-line treatment with debulking surgery and chemotherapy. Although therapeutic options for targeted therapy are rapidly expanding, identification of patients who respond to these therapies remains a challenge. In recognition of the importance of the functional phenotype of cancer cells, Verhaegh et al. (Cancer Res 2014) developed assays to measure functional activity of signal transduction pathways (STPs) based on mRNA expression levels of pathway-specific target genes. In this study, we aimed to identify HGSCs with STP activity with potential clinical target by comparing their activity assessment with STP activity in normal Fallopian tube epithelium (FTE), the tissue of origin of most HGSCs. Methods: We included 67 primary tumor samples taken prior to start of chemotherapy of postmenopausal patients diagnosed with advanced stage HGSC and 8 morphologically normal FTE samples of healthy postmenopausal women. Using OncoSignal pathway assays, we assessed functional pathway activity of the androgen receptor (AR), estrogen receptor (ER), PI3K, Hedgehog, TGF-𝛽 and Wnt pathways. Differences in STP activity between groups were compared with Mann-Whitney U tests. Cut-off value for aberrant STP activity was defined as two standard deviations above the mean value of STP activity measured in FTE samples. Results: In the HGSC group we observed lower median ER (p < 0.001) and Wnt (p = 0.046) pathway activity and higher median PI3K (p = 0.025) and TGF-𝛽 pathway (p = 0.030) activity as compared to the normal FTE group. In individual HGSC samples, aberrant activity was identified for the AR (n = 14), PI3K (n = 16), Hedgehog (n = 4), TGF-𝛽 (n = 36) and Wnt (n = 10) pathways. Frequently observed combinations of aberrant STP activity were AR/TGF-𝛽 (n = 8), TGF-𝛽/Wnt (n = 6) and PI3K/Hedgehog (n = 3). In total, we identified at least one STP with potential clinical target in 52 of the 67 HGSC samples. Conclusions: Our analysis enabled the identification of STP activity with potential clinical target in 78% of the analyzed HGSC samples. Differentiation between normal and aberrant STP activity could have clinical utility in the selection of HGSC patients for targeted therapy.

A Case of Personalized Management of Carcinoma of Fallopian Tube Harboring BRCA Mutation and Sister Mary Joseph's Nodule

Fallopian tube malignancies have been presumed to rare incidence with dismal prognosis. However, recent data suggest that the true incidence of PFTC has been substantially underestimated. Early diagnosis of fallopian tube cancer seems difficult. The routes of metastasis of fallopian tube carcinoma are similar to those of ovarian cancer. Genetic factors are relatively important risk factors for tubal cancer. Poly ADP -ribose polymerase inhibitor is used for BRCA-mutant PFTC. In this artical, we use a rare case of navel metastatic tumor which finally be confirmed that it is originated from fallopian tube to discovered the hereditary factors through genetic testing, and reported this case to provide preventive intervention for the next generation of eugenics and incidence.