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Background: The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns similar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone., Methods: The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchronous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endometrioid cancers, and stage IA cancers., Results: Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers., Conclusions: We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy., Impact: The possible misdiagnosis associated with clinicopathologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level., (©2022 American Association for Cancer Research.)

Objective: Although experimental models suggest that use of beta-blockers, a common antihypertensive agent, may improve survival in ovarian cancer patients, results from clinical studies have been mixed., Methods: We evaluated the associations of pre-diagnostic (n = 950) and post-diagnostic (n = 743) use of antihypertensive medications with survival among patients with invasive, epithelial ovarian cancer in the Nurses' Health Study (NHS; 1994-2016) and NHSII (2001-2017), with follow-up until 2018 and 2019, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) for ovarian cancer mortality according to antihypertensive medication use before and after diagnosis, considering multiple drug classes (beta-blockers, calcium-channel blockers, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors)., Results: After adjusting for age, BMI, smoking status and tumor characteristics, pre-diagnostic use versus non-use of calcium-channel blockers was associated with higher ovarian cancer mortality (HR: 1.49; 95% CI: 1.13, 1.96), which was primarily due to polytherapy involving calcium-channel blockers (HR: 1.61; 95% CI: 1.15, 2.26). Pre-diagnostic use of beta-blockers, thiazide diuretics, or ACE inhibitors was not associated with ovarian cancer mortality. No association was observed for post-diagnostic antihypertensive medication use individually or in combination, except for lower mortality associated with polytherapy involving ACE inhibitors (HR: 0.53; 95% CI: 0.31, 0.91)., Conclusion: Overall, we did not find clear relationships between antihypertensive medication use and ovarian cancer mortality. However, given the limitation of the data, we cannot determine whether the association may differ by type of beta-blockers. The reasons underlying the observed associations with pre-diagnostic calcium-channel blocker use and post-diagnostic ACE inhibitor use require further investigation., Competing Interests: Declaration of Competing Interest Scientific advisory board, Kiyatec, shareholder,Biopath, research funding, M-Trap, and consulting, Merck (A.K.S.), (Copyright © 2021 Elsevier Inc. All rights reserved.)

The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, is not well understood. Here, we perform comprehensive multi-platform omics analyses, including integrated analysis, and immune monitoring on primary and metastatic sites from highly clinically annotated HGSC samples based on a laparoscopic triage algorithm from patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent or poor response. We identify significant distinct molecular abnormalities and cellular changes and immune cell repertoire alterations between the groups, including a higher rate of NF1 copy number loss, and reduced chromothripsis-like patterns, higher levels of strong-binding neoantigens, and a higher number of infiltrated T cells in the R0 versus the NACT groups., Competing Interests: Declaration of Interests A.A.J. consults with Roche/Genentech, Aravive, and Almac Group; has research funding from AstraZeneca, Pfizer, Bristol-Myers Squibb, Immatics, Iovance Biotherapeutics; honoraria from Gerson Lehrman Group; and travel support from AstraZeneca and MedImmune. K.R., A.D., and D.C. are employees of Akoya Biosciences. N.D.F. consults with Tesaro. S.N.W. has clinical research grants from AstraZeneca, ArQule, Bayer, Clovis Oncology, Cotinga Pharmaceuticals, NCCN, Novartis, Roche/Genentech, and Tesaro and consults with AstraZeneca, Circulogene, Clovis Oncology, Merck, Novartis, Pfizer, Roche/Genentech, Takeda, and Tesaro. R.L.C. has clinical research grants from AstraZeneca, Merck, Clovis Oncology, Genmab, Roche/Genentech, Janssen, V Foundation, and Gateway for Cancer Research and consults with AstraZeneca, Merck, Tesaro, Medivation, Clovis Oncology, Genmab, GamaMabs, Agenus, Regeneron, OncoQuest, OncoSec, Roche/Genentech, and Janssen. G.B.M. consults with AstraZeneca, ImmunoMet, Ionis, Nuevolution, PDX Phamaceuticals, SignalChem, Symphogen, and Tarveda Therapeutics; has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindletop Captial, and Tarveda Therapeutics; sponsored research from AstraZeneca, ImmunoMet, Pfizer, NanoString, and Tesaro and travel support from Chrysallis BioTherapeutics; and has licensed technology to NanoString and Myriad Genetics. Y.C.’s spouse owns stock in Celsion. T.P.C. consults with Thermo Fisher Scientific and has research funding from AbbVie. G.L.M. consults with Merck, Kiyatek, Renovia, and Tesaro and has research funding from Merck. A.K.S. consults with Merck and Kiyatec, has research funding from M-Trap, and is a shareholder of Bio-Path Holdings. All other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Establishing an accurate histologic diagnosis is essential for determining the appropriate course of therapy for ovarian cancer. This study sought to investigate and describe nonovarian cancer pathologies discovered during the systematic laparoscopic workup of presumed advanced ovarian cancer., Methods: A retrospective cohort of patients with presumed advanced ovarian cancer (based on elevated CA125 and/or imaging) presenting to our center without confirmed pathologic diagnosis were identified and characterized. Patients without ovarian cancer on final pathology were described and compared with those with confirmed epithelial ovarian cancer using standard statistical methods., Results: Nonovarian cancer was found in 26 (7.1%) of 365 cases over 3.5 years of study, and included benign ovarian pathology, and metastatic uterine, breast, and gastrointestinal cancers. Most nonovarian cancer cases could not be diagnosed with percutaneous biopsy, and instead used diagnostic laparoscopy or assessment at the time of laparotomy for diagnosis (58%). No patient received inappropriate treatment. Nonovarian cancer cases were more likely to be nonwhite (P = 0.003), have a better Eastern Cooperative Oncology Group performance status (P < 0.001), and have a lower CA125 value (P < 0.001), and were less likely to have pleural effusions (P = 0.04)., Conclusions: A systematic laparoscopic triage approach to advanced-stage ovarian cancer eliminates incorrect neoadjuvant chemotherapy administration and inappropriate laparotomy. This algorithm identified a population of women who are more likely to have nonovarian cancer pathology. Increasing screening efforts should be focused on conclusive diagnosis with the least invasive testing possible.

Thrombocytosis is present in more than 30% of patients with solid malignancies and correlates with worsened patient survival. Tumor cell interaction with various cellular components of the tumor microenvironment including platelets is crucial for tumor growth and metastasis. Although it is known that platelets can infiltrate into tumor tissue, secrete pro-angiogenic and pro-tumorigenic factors and thereby increase tumor growth, the precise molecular interactions between platelets and metastatic cancer cells are not well understood. Here we demonstrate that platelets induce resistance to anoikis in vitro and are critical for metastasis in vivo. We further show that platelets activate RhoA-MYPT1-PP1-mediated YAP1 dephosphorylation and promote its nuclear translocation which induces a pro-survival gene expression signature and inhibits apoptosis. Reduction of YAP1 in cancer cells in vivo protects against thrombocytosis-induced increase in metastasis. Collectively, our results indicate that cancer cells depend on platelets to avoid anoikis and succeed in the metastatic process.Platelets have been associated with increased tumor growth and metastasis but the mechanistic details of this interaction are still unclear. Here the authors show that platelets improve anoikis resistance of cancer cells and increase metastasis by activating Yap through a RhoA/MYPT-PP1 pathway.

Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management. Here, we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image and chemically characterize the metabolic profiles of HGSC, BOT, and normal ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine papillary branches in serous BOT and allowed for characterization of spatial features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC. Predictive markers of cancer aggressiveness were identified, including various free fatty acids, metabolites, and complex lipids such as ceramides, glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification models built from a total of 89,826 individual pixels, acquired in positive and negative ion modes from 78 different tissue samples, enabled diagnosis and prediction of HGSC and all tumor samples in comparison with normal tissues, with overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination was achieved with an overall accuracy of 93.0%. Interestingly, our classification model allowed identification of three BOT samples presenting unusual histologic features that could be associated with the development of low-grade carcinomas. Our results suggest DESI-MS as a powerful approach for rapid serous ovarian cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903-13. ©2017 AACR ., (©2017 American Association for Cancer Research.)