Ovarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant to apoptosis and chemotherapeutic agents. However, the precise mechanism as an oncogenic addiction that makes 3D spheroids resistant to apoptosis and chemotherapeutic agents is not understood. To study the signaling addiction mechanism that occurs during cancer progression in patients, we developed an endometrioid subtype ovarian cancer cell line named ‘MCW-OV-SL-3’ from the ovary of a 70-year-old patient with stage 1A endometrioid adenocarcinoma of the ovary. We found that the cell line MCW-OV-SL-3 exhibits interstitial duplication of 1q (q21–q42), where this duplication resulted in high expression of the PIK3C2B gene and aberrant activation of PI3K-AKT-ERK signaling. Using short tandem repeat (STR) analysis, we demonstrated that the cell line exhibits a unique genetic identity compared to existing ovarian cancer cell lines. Notably, the MCW-OV-SL-3 cell line was able to form 3D spheroids spontaneously, which is an inherent property of tumor cells when plated on cell culture dishes. Importantly, the tumor spheroids derived from the MCW-OV-SL-3 cell line expressed high levels of c-Kit, PROM1, ZEB1, SNAI, VIM, and Twist1 compared to 2D monolayer cells. We also observed that the hyperactivation of ERK and PI3K/AKT signaling in these cancer cells resulted in resistance to cisplatin. In summary, the MCW-OV-SL3 endometrioid cell line is an excellent model to study the mechanism of cancer stemness and chemoresistance in endometrioid ovarian cancer.

To determine the incidence of lower-extremity lymphedema after surgical therapy including lymphadenectomy in endometrial cancer patients using standardized leg measurements. Also, to determine additional risk factors for the development of lymphedema and to study the effect of lymphedema on one's quality of life. In this prospective cohort study, patients with the diagnosis of endometrial cancer who were to undergo definitive surgical management were evaluated pre-operatively and followed post-operatively over the course of two years. Standardized leg measurements were performed by the same individuals at six time-points. Subjects also completed a standardized quality-of-life survey at each time-point. The incidence of lymphedema in 39 women with endometrial cancer using a standardized leg measurement protocol was 12.8% with lymphedema defined as a 20% increase in post-operative leg measurements. There was no significant association between the development of lymphedema and the number of pelvic or para-aortic lymph nodes removed, medical comorbidities, or surgical approach (p > 0.05). Of the five patients who met criteria for lymphedema, only one had worsening quality-of-life concerns post-operatively on the FACT-En, version 4, survey. This is the first prospective study using standardized leg measurements to calculate the incidence of post-operative lymphedema in endometrial cancer. Medical comorbidities, surgical approach, number of lymph nodes removed, and location of lymph nodes removed did not appear to affect the development of lymphedema in this cohort. A prospective, multicenter trial is needed to confirm these findings and to further assess the impact of lymphedema on one's quality of life.

The authors would like to correct the author byline to include Dr

Adult granulosa cell tumors (AGCTs) are rare ovarian tumors with generally good prognosis after surgical resection; however, they do have recurrence potential. Therapeutic and management options for recurrences are currently limited, and the need for expanded adjuvant therapies is increasingly recognized. Anti-hormonal therapy is being explored as an option, which relies on the detection and assessment of hormone receptor expression (androgen, estrogen, and progesterone receptors) as a biomarker and therapeutic target. Our study identifies several clinicopathologic characteristics with significant associations for recurrence of AGCT, which were younger age, higher stage, and larger tumor size. Our study also demonstrates that androgen receptor (AR) expression may be utilized as a potential biomarker for hormonal therapy and that detection of AR expression in AGCT by immunohistochemistry (IHC) varies depending on the antibody clone used for testing. AR was detected in 95% of samples tested with antibodies derived from clone AR27. This detection rate is much higher than previously reported.

Folate receptor-α (FRα) is overexpressed in a subset of high-grade endometrial cancers, but the activity and molecular effects of the FRα-targeting antibody–drug conjugate mirvetuximab soravtansine (MIRV) in this disease are undefined. Mice bearing two FRα-positive high-grade recurrent high-grade endometrial cancer patient-derived xenografts (PDXs; UT42, UT150) were randomized to a single tail vein injection of MIRV (5 mg/kg) or phosphate-buffered saline (control); a separate UT150 cohort received a second dose on Day 9. Tumors harvested 24 hours after treatment underwent microarray profiling and Hallmark, KEGG, and Gene Ontology pathway scoring. MIRV significantly inhibited tumor growth in both models, and a second dose produced more durable suppression (P<0.03). FRα protein expression was maintained after MIRV treatment. In both models, MIRV induced E2F target (z = 8.1 and 4.5) and G2/M checkpoint (z = 4.4 and 3.9) programs, consistent with DM4-induced mitotic arrest. MIRV also suppressed hypoxia (z = −6.4 and −11.6), epithelial–mesenchymal transition (EMT; z = −4.6 and −10.1), glycolysis and interferon-γ response programs. Genes reduced in both models (n = 117; 66 expected by chance) were enriched for TNFα/NF-κB, IL2–STAT5, EMT, and hypoxia signaling (FDR ≤ 0.002). These exploratory findings support evaluating MIRV-based combinations, including with anti-angiogenic agents, in endometrial cancer.