Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image–based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model’s decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Lee JY, et al. J Gynecol Oncol. 2017 Jul;28(6):e73. https://doi.org/10.3802/jgo.2017.28.e73

Mesonephric-like adenocarcinoma (MLA) arising in the ovary is a rare malignant tumor of the female genital tract. Although the clinicopathological and molecular characteristics of uterine MLA have been accumulated, those of ovarian MLA have not been firmly clarified. In this study, we investigated the clinicopathological, immunohistochemical, and genetic features of five ovarian MLAs. A review of electronic medical records and pathology slides, immunostaining, and targeted sequencing was performed. On imaging, ovarian MLA presented as either a mixed solid and cystic mass or a purely solid mass. One, three, and one patient were diagnosed as having FIGO stage IA, IC, and II MLA, respectively. Four patients with stage IC–II tumor underwent post-operative adjuvant chemotherapy. Three of the four patients whose follow-up information was available did not experience recurrence. In contrast, the remaining patient with stage IA tumor who did not receive any adjuvant treatment developed multiple metastatic recurrences at post-operative 13 months. Histologically, ovarian MLAs characteristically displayed architectural diversity, compactly aggregated small tubules, and eosinophilic intraluminal secretions. Four tumors were found to be associated with endometriotic cysts. Two cases showed some areas of high-grade nuclear atypia, brisk mitotic activity, and necrosis. Immunohistochemically, all cases showed positive immunoreactivities for at least three of the four examined mesonephric markers (GATA3, PAX2, TTF1, and CD10), lack of WT1 expression, non-diffuse p16 immunoreactivity, and wild-type p53 immunostaining pattern. Targeted sequencing analysis revealed that all four examined cases harbored pathogenic KRAS mutations: p.G12V (2/4); p.G12D (1/4); and p.G12C (1/4). In addition, we reviewed the previous literature reporting 60 cases of ovarian MLA. Our findings corroborate those of the previous data regarding the clinical presentation, histological features, immunophenotypes, and molecular alterations. Our observations should encourage pathologists to recognize and accurately diagnose this rare but distinct entity.

Background/Aim: Uterine mesonephric-like adenocarcinoma (MLA) is a rare malignant tumor of the female genital tract. Patients and Methods: We reviewed 237 endometrial carcinoma cases and investigated the clinicopathological and molecular characteristics of uterine MLA. Results: We found that 3.0% (7/237) of the endometrial carcinoma cases were MLAs. Compared to endometrial endometrioid carcinoma, MLA showed larger tumor size, deeper myometrial invasion, increasingly advanced-stage disease, and more frequent lymphovascular space invasion. All MLAs exhibited architectural diversity, compactly aggregated small tubules, eosinophilic intraluminal secretions, overlapped and angulated nuclei, scant cytoplasm, and presence of spindle cells. All the MLAs expressed at least two mesonephric markers. All except one MLA harbored activating Kirsten rat sarcoma viral oncogene homolog mutations. All patients with MLA developed postoperative metastases. MLA had the lowest progression-free survival rate among different histological types of endometrial carcinoma. Conclusion: Uterine MLA is a highly aggressive gynecological malignancy, showing unique morphological and molecular features, frequent recurrences and metastases, as well as poor prognosis.

Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer