The clinical relevance of mismatch repair deficiency (MMRd) in patients with early-stage cancer remains unclear. Our goal was to investigate the prognostic role of MMRd in patients with colorectal and endometrial cancer.
From 05/1990 to 03/2013, formalin-fixed paraffin-embedded primary tumors were prospectively collected from patients with early-stage colorectal (991) and endometrial (167) cancer, referred to the Departments of Medical Oncology affiliated with the Hellenic Cooperative Oncology Group. Protein expression of MMR proteins was evaluated by immunohistochemistry. The primary outcome measure was overall survival (OS).
Overall, 1158 patients were included (median age, 64 years). Stage III disease was diagnosed in 58% and 19% of patients with colorectal and endometrial cancer, respectively. All patients with colorectal cancer but only 13% of those with endometrial cancer received adjuvant treatment. MMRd was observed in 114 (11.5%) of colorectal and 80 (48%) of endometrial tumors. MMRd was associated with younger age at diagnosis (62 vs. 60y, Mann-Whitney, p = 0.003), higher tumor grade (26.3% vs 16.5%, chi-square, p < 0.001) and lower tumor stage (72% vs. 42.6%, p < 0.001). Colorectal MMRd tumors were more likely right-sided (64.6% vs. 27.2%, p < 0.001), and with a mucinous component (63.7% vs. 41.4%, p < 0.001). Endometrial MMRd tumors were more often endometrioid (74/144, 51.4%) than serous/clear cell (3/15, 20%) carcinomas (p = 0.020). Compared to MMR proficiency, MMRd was associated with improved OS in the entire cohort (HR = 0.66, 95% CI 0.47-0.92, Wald’s p = 0.013) and in patients with endometrial cancer, (HR = 0.39, 95% CI 0.20-0.77, p = 0.006) but not in patients with colorectal cancer (HR = 0.73, 95% CI 0.49-1.09, p = 0.120). In multivariate analysis adjusting for tumor type, stage and grade, MMRd maintained its favorable prognostic significance in the entire cohort (Wald’s p = 0.014) and in patients with endometrial cancer (p = 0.017).
MMRd is associated with improved outcomes in patients with early-stage endometrial cancer, but not in patients with early-stage colorectal cancer.
Clinical trial identification
Legal entity responsible for the study
Hellenic Cooperative Oncology Group.
Hellenic Cooperative Oncology Group Internal Research Grant.
All authors have declared no conflicts of interest.