Prognostic Implications of Combined p53 and Mismatch-Repair Immunophenotypes in Uterine Carcinosarcoma

Background and Objectives: Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecologic malignancy with poor clinical outcomes and limited therapeutic options. This study investigated the prognostic significance of molecular subgroups defined by p53 expression and mismatch repair (MMR) status in UCS. Materials and Methods: This retrospective study included 51 patients with uterine carcinosarcoma who underwent surgical treatment between 2010 and 2023. Immunohistochemical analyses were performed to evaluate p53 expression (wild-type vs. aberrant) and MMR status (intact vs. deficient). Patients were classified into four molecular subgroups: p53wt/MMR-intact (n = 15), p53abn/MMR-intact (n = 24), p53wt/MMR-deficient (n = 9), and p53abn/MMR-deficient (n = 3). Clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) were analyzed. Additional component-specific analyses were performed for carcinomatous and sarcomatous tumor elements. Results: The median follow-up period was 34 months, and the overall mortality rate was 51.0%. Patients with p53wt/MMR-deficient tumors demonstrated the most favorable outcomes, with a mean OS of 92.9 ± 22.1 months and a mortality rate of 33.3%. In contrast, the p53abn/MMR-intact subgroup showed the poorest survival outcomes (mean OS: 54.4 ± 11.6 months; mortality rate: 62.5%). Although Kaplan-Meier survival analysis did not demonstrate statistically significant differences between molecular subgroups (p = 0.783), distinct prognostic trends were observed. Multivariate Cox regression analysis identified age and lymph node involvement as independent predictors of both OS and DFS. Component-specific analyses demonstrated significant associations between aberrant p53 expression in the carcinomatous component and epithelial subtype distribution (p = 0.025) as well as myometrial invasion patterns (p = 0.040). Conclusions: Combined p53/MMR-based immunohistochemical classification demonstrated distinct prognostic trends in uterine carcinosarcoma. These findings suggest that molecular stratification could support risk assessment and therapeutic decision-making in UCS. Larger prospective multicenter studies are warranted to validate these findings and clarify their potential clinical implications.