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BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Pure ductal-type mesonephric remnants in the uterine cervix are rare. We report an unusual case in a 31-yr-old of cervical mesonephric remnants of predominantly ductal type exhibiting seminal vesicle-like differentiation in a female-to-male transgender patient receiving long-term testosterone therapy. To the best of our knowledge, this phenomenon has not been previously reported. The impact of testosterone on the female genital tract is likely to be encountered more frequently due to increasing rates of gender-affirming surgery, including long-term androgen use. Awareness of the morphologic features is important as such changes may be misinterpreted as premalignant or malignant lesions. In reporting this unusual case, we briefly review lesions derived from cervical mesonephric remnants and testosterone-associated changes in the female genital tract., Competing Interests: The authors declare no conflict of interest., (Copyright © 2025 by the International Society of Gynecological Pathologists.)

Introduction: Borderline ovarian tumours (BOT) are a common epithelial ovarian tumours. Typically diagnosed at an early stage with a good prognosis, many BOT are treated conservatively. Recurrence is common. This update to our last audit in 1997 represents one of the largest audits of BOT to date., Materials and Methods: All patients with BOT managed at 'the hospital' from 1984 to 2021 were included. Expert pathology review was available., Results: There were 549 cases included. The recurrence rate was 5% (n = 29/549) with 1.4% (n = 8/549) undergoing malignant transformation. Three of the eight women who recurred as cancer died from their disease. Frozen section was predictive of histologic diagnosis in 92% (n = 55/60) of serous tumours (SBOT), but only 62% (n = 54/87) of mucinous tumours (MBOT). In MBOT where the appendix appeared normal intra-operatively, it was histologically benign in all cases (n = 63). In SBOT, the recurrence rate was 5/23 (22%), 12/52 (23%), 1/29 (3%) and 3% (P = <0.01) for unilateral cystectomy, unilateral oophorectomy ± cystectomy, bilateral oophorectomy, and bilateral oophorectomy with hysterectomy, respectively, as index procedure. In MBOT this correlated to 2/20 (10%), 3/93 (3%), 0 and 1/58 (2%), respectively., Discussion: This study describes important information correlating first surgical procedure and fertility-sparing surgery to recurrence and malignant transformation. For all BOT subtypes, fertility-preserving surgery increased the risk of recurrence and hysterectomy was not superior to removal of both ovaries. In MBOT, frozen section is of limited utility and the macroscopically normal appendix is very unlikely to be anything but benign, if MBOT is the true histologic diagnosis., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features., Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting., Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations., Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271 ., (©2020 American Association for Cancer Research.)

Background: High grade epithelial ovarian cancer (EOC) is commonly characterised by widespread peritoneal dissemination and ascites. Metastatic EOC tumour cells can attach directly to neighbouring organs or alternatively, maintain long term tumourigenicity and chemoresistance by forming cellular aggregates (spheroids). Cancer stem-like cells are proposed to facilitate this mechanism. This study aimed to investigate the role of Oct4A, an embryonic stem cell factor and known master regulator of pluripotency in EOC progression, metastasis and chemoresistance., Methods: To investigate the expression of Oct4A in primary EOC tumours, IHC and qRT-PCR analyses were used. The expression of Oct4A in chemonaive and recurrent EOC patient ascites-derived tumour cells samples was investigated by qRT-PCR. The functional role of Oct4A in EOC was evaluated by generating stable knockdown Oct4A clones in the established EOC cell line HEY using shRNA-mediated silencing technology. Cellular proliferation, spheroid forming ability, migration and chemosensitivty following loss of Oct4A in HEY cells was measured by in vitro functional assays. These observations were further validated in an in vivo mouse model using intraperitoneal (IP) injection of established Oct4A KD clones into Balb/c nu/nu mice., Results: We demonstrate that, compared to normal ovaries Oct4A expression significantly increases with tumour dedifferentiation. Oct4A expression was also significantly high in the ascites-derived tumour cells of recurrent EOC patients compared to chemonaive patients. Silencing of Oct4A in HEY cells resulted in decreased cellular proliferation, migration, spheroid formation and increased chemosensitivity to cisplatin in vitro. IP injection of Oct4A knockdown cells in vivo produced significantly reduced tumour burden, tumour size and invasiveness in mice, which overall resulted in significantly increased mouse survival rates compared to mice injected with control cells., Conclusions: This data highlights a crucial role for Oct4A in the progression and metastasis of EOC. Targeting Oct4A may prove to be an effective strategy in the treatment and management of epithelial ovarian tumours.