Clinical Outcome and Morphology-Based Analysis of p53 Aberrant and Mismatch Repair Protein-Deficient Ovarian Clear Cell Carcinoma and Their Association With p16, HER2, and PD-L1 Expression.

Abstract

We studied the prevalence and prognostic significance of mismatch repair deficient (MMRD) and p53 aberrant ovarian clear cell carcinoma (CCO) and their association with other prognostic and theranostic biomarkers (p16, HER2, PD-L1). We also aimed to identify morphologic features to serve as screening tools for immunohistochemical testing for these biomarkers. Tissue microarrays with 3-mm cores from 71 pure CCOs were immunostained with PMS2, MSH6, p53, p16, HER2, and PD-L1. Expression status was correlated with tumor recurrence/disease progression and survival. It was also correlated with morphologic features (tumor size, nuclear grade, tumor architecture, mitotic activity, presence of endometriosis, tumor budding, and tumor inflammation). p53 aberrant tumors were associated with shorter overall and recurrence-free survivals (P = .002 and P = .01, respectively). In multivariate analysis, p53 aberrant status and tumor stage were independently associated with recurrence/disease progression (hazard ratio [HR] = 3.31, P = .037 and HR = 1.465, P = .004, respectively). p53 aberrant status was associated with tumor budding (P = .037). MMRD, p16, HER2, and PD-L1 expression had no prognostic significance. HER2 and PD-L1 were expressed in 56% and 35% of tumors, respectively. MMRD was associated with tumor expression of PD-L1 (P > .05) but not with tumor inflammation. Aberrant p53 in CCO is infrequent but associated with poor prognosis independent of stage. Presence of tumor budding could be a screening tool for p53 testing. High prevalence of HER2 and PD-L1 expression indicates the eligibility of patients with CCO for ongoing clinical trials using these therapeutic targets.