Zhiyong Liang

Identifying Serum Small Extracellular Vesicle MicroRNA as a Noninvasive Diagnostic and Prognostic Biomarker for Ovarian Cancer

There remains a lack of effective and noninvasive methods for the diagnosis and prognosis prediction of epithelial ovarian carcinoma (EOC). Here, we investigated the possibility of serum-derived small extracellular vesicle (sEV) microRNAs (miRNAs) as potential biomarkers for distinguishing between benign and malignant adnexal masses and predicting the prognosis of EOC patients. A serum sEV miRNA model for identifying the EOC (sEVmiR-EOC) was successfully established in the training cohort. Furthermore, the sEVmiR-EOC model was confirmed in the testing cohort and validation cohort, demonstrating robust diagnostic accuracy. The sEVmiR-EOC model showed better performance than carbohydrate antigen 125 (CA125) in discriminating patients with stage I EOC from benign patients. Using EOC samples and follow-up data, we identified miR-141-3p and miR-200c-3p as potential prognostic predictors. Finally, we confirmed the change of the sEVmiR-EOC RiskScore between the preoperative and postoperative samples and found that the sEVmiR-EOC model could predict the prognosis of EOC patients.

Prevalence of Atypical and Subclonal p53 Immunohistochemistry Expression in Mismatch Repair Deficient and/or POLE-Mutant Endometrial Carcinomas with TP53 Mutation

p53 Immunohistochemistry (IHC) is a reliable surrogate for determining TP53 mutation status in endometrial carcinomas (ECs). However, the correlation of p53 IHC patterns and TP53 mutation characteristics in mismatch repair deficiency (MMRd) and/or POLE-mutant ECs was not comprehensively investigated. In this study, we identified 4 p53 expression patterns in 40 MMRd and/or POLE-mutant ECs with TP53 mutations. Thirteen cases (33%) displayed a wild-type pattern. Nine cases (23%) showed atypical pattern, characterized by the presence of eye-catching clustered cells with strong nuclear staining or weak-to-moderate cytoplasmic staining, which were patchily distributed with blurred boundaries. Fourteen cases (35%) demonstrated subclonal pattern with distinct regions of wild-type and mutation-type staining, of which 3 cases were originally misdiagnosed as "mixed EC." Only 4 (10%) cases exhibited typical aberrant pattern. Tumors with wild-type and atypical patterns were predominantly associated with MMRd and POLE mutations, respectively. Among 52 TP53 mutations identified, 75% were missense and 25% were truncating, predominantly in DNA-binding domain. Gain-of-function missense mutations were more frequent in cases with subclonal patterns, whereas non-gain-of-function missense mutations predominated in wild-type or atypical patterns. Concurrent mutations were present in 25% of cases and were more common in aberrant or atypical patterns. Interestingly, 2 POLE wild-type cases with subclonal MMR expression showed p53 overexpression across the entire tumor, complicating molecular subtyping. These findings highlight the prevalence of atypical and subclonal p53 expression patterns in MMRd and/or POLE-mutant ECs with TP53 mutations, aiding in accurate IHC interpretation and thus more precise EC histological and molecular classification.