Mismatch Repair Status as a Predictor of Benefit From Platinum-Based Adjuvant Therapy in Ovarian Clear Cell Carcinoma

Background: Previous studies have indicated that patients with colorectal cancer who demonstrate defective DNA mismatch repair (dMMR) have clinical and pathologic features that distinguish them from patients who have proficient mismatch repair (pMMR) tumors. However, the influence of mismatch repair (MMR) status in ovarian clear cell carcinoma (OCCC) is still unknown. Aim: To evaluate the MMR statuses in OCCC and its correlation with clinicopathological and prognostic characteristics. Methods: MMR statuses were measured by tissue microarray–based immunohistochemistry from 120 OCCC patients. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. Results: Overall, 120 OCCC patients met the entry criteria and their MMR status were detected, consisting of 24 patients with dMMR and 96 patients with pMMR. Tumors with dMMR were strongly associated with platinum-sensitive disease ( P = 0.008) and large tumor volume ( P = 0.028). Among all the patients who have received surgery, tumors with dMMR had a better progression-free survival and overall survival (OS) than those with pMMR (hazard ratio [HR] for recurrence, 0.459 [95% confidence interval (95% CI), 0.224-0.940]; P = 0.029; HR for death, 0.381 [95% CI, 0.170-0.853]; P = 0.015). In subgroup analysis, dMMR patients experienced a better PFS (HR, 0.242; P = 0.055) and OS (HR, 0.141; P = 0.039) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with more favorable prognosis than dMMR in platinum-resistant patients (PFS, HR: 0.317, P = 0.052; OS, HR: 0.370, P = 0.046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR, 5.938; [95% CI, 2.804-12.574], P < 0.001) and OS (HR, 6.209; [95% CI, 2.724-14.156], P < 0.001). Conclusion: MMR status in ovarian clear cell carcinoma is not only a prognostic indicator, but also appears to be a possible predictor for the use of platinum-based adjuvant chemotherapy.