C-Kit and MSI in stage II colorectal cancer: Incidence and prognosis in Egyptian patients

Abstract

Introduction: Stage II represents a peculiar state in the management of colorectal cancer (CRC). Clinicopathologic staging often does not provide sufficient prognostic information to determine patients with high risk of recurrence to warrant adjuvant therapy. Development of molecular prognostic and predictive markers are the best strategies to improve prognostic assessment and likelihood to benefit from adjuvant chemotherapy.The aim of this study is to evaluate the prognostic value of MSI and c-kit as well as clinicopathological factors in stage II CRC. Methods: The study included patients with stage II CRC who underwent curative surgical resection and had available archival tumor tissue who were treated and followed up in the NCI, Cairo University in the period between January 2006 till January 2016. Ckit was assessed by IHC while MSI was assessed by PCR. Results: Out of the 60 cases assessed, MSI-Hstatus was encountered in 29 cases (48.3%) while c-kit overexpression was found in 19 cases (33.3%) out of 57 assessed patients. In univariate analysis, performance status (PS), diabetes mellitus, family history of malignancy and tumor (T) stage were significantly correlated with DFS (p=0.010, p=0.028, p=0.05 and p=0.007 respectively) while PS and T stage were significantly correlated with OS (p=0.006 and p=0.05 respectively). C-kit over expression had no impact on either DFS (p=0.112) or OS (p=0.29) while low or stable MSI expression was associated with significantly worse OS and DFS (p=0.001). In multivariate analysis, MSI was found to be independent prognostic factor for DFS and OS. Conclusion: Tumor (T) stage and MSI are the best factors to determine prognosis and adjuvant treatment decision in stage II CRC cases. Patients with T3 and/or MSI-H seem to less benefit from adjuvant chemotherapy. C-kit needs larger trials to assess its actual role.