KRAS/NRAS Mutational Analysis and Clinicopathologic Correlation of Colorectal Carcinoma: A Single Institute Experience From Turkey

Background: Colorectal carcinoma (CRC) is the second most frequent cause of cancer-related death for both sexes. Clinical and pathological correlates of Kirsten rat sarcoma viral oncogene/neuroblastoma ras viral oncogene (KRAS/NRAS) mutant tumors are important for therapy response, especially in metastatic CRCs. The aim of this study is to determine the frequency of KRAS/NRAS mutations and investigate the clinicopathologic characteristics of KRAS/NRAS mutant and rat sarcoma (RAS)-wild type CRCs. Methods: Pathology archives were searched for CRCs between 2014 and 2015, retrospectively. We reevaluated tumor slides for Crohn-like infiltrate, tumor infiltrating lymphocytes, tumor budding, presence of mucinous component, and signet-ring cell morphology. Tumor grade, depth of invasion, lymph node metastases, distant metastases, lymphovascular and perineural invasion, polyp type, and DNA mismatch repair status were derived from their pathology reports. Formalin-fixed, paraffin-embedded tissues were examined for KRAS/NRAS mutation status. Mutation status and their clinicopathologic correlates were evaluated. Results: KRAS and NRAS mutations were detected in 43.6% and 10% of the CRCs, respectively. KRAS mutations were associated with multiple organ metastasis and CRCs with solid growth pattern did not harbor RAS mutations. Well differentiated CRCs were more common in NRAS mutant and RAS-wild type CRCs in comparison to RAS mutant tumors. NRAS mutant CRCs were more frequent in the left colon and rectum. Conclusion: In this study, we identified that KRAS mutations were associated with multiple organ metastasis and CRCs with solid growth pattern did not harbor RAS mutations. Also, NRAS mutant tumors were more common in the left colon and rectum concordant with the previous studies. Keywords: colorectal carcinoma, metastatic colorectal carcinoma, KRAS, NRAS