Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis

Introduction: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. Objective: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. Methods: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted. Results: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. Conclusion: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs