p53 Normal and p53 Abnormal Clear Cell Ovarian Carcinomas: Clinical Characteristics and Biomarker Profiles

A new concept of molecular classification for clear cell ovarian carcinoma (CCOC) has been proposed: TP53 wild-type and TP53 mutated. Our aim was to evaluate this classification at the immunohistochemical level in p53 normal and abnormal subgroups. Clinicopathologic factors and 12 immunohistochemical biomarkers (p53, PR, ER, β-catenin, vimentin, ARID1A, HNF1-β, E-cadherin, c-erb-B2, MIB-1, p16, and L1CAM) and patient prognosis were analyzed in 132 CCOCs. The p53 abnormal group presented with significantly worse disease-specific overall survival (DSS) and disease-free survival (DFS) than the p53 normal group, which was largely due to higher stage and a more frequent presence of residual tumor in the p53 abnormal group. Furthermore, higher stage and presence of residual tumor were markers of poor outcome within both p53 subgroups. Interestingly, the presence of ascites was related to shorter DSS only in p53 normal cases. The p53 normal group was also characterized by a higher frequency of ARID1A loss and HNF1-β positivity, whereas p16 overexpression and ER positivity were more common in p53 abnormal cases. Interestingly, ARID1A loss correlated with poor DSS in the p53 abnormal group. In the p53 normal tumors, ER positivity was associated with better DSS and p16 positivity with worse DFS. L1CAM positivity was associated with residual tumor only in the p53 normal group. Our findings support the existence of 2 distinct molecular subgroups of CCOC, p53 normal and p53 abnormal, with diverse characteristics and patient outcomes. Clinical and molecular differences were discovered within these subgroups.