Site-specific Differences in Colonic Adenocarcinoma KRAS Mutations and High Tumor Budding Are More Frequent in Cecal Adenocarcinoma

Recent literature indicates that adenocarcinomas of the cecum differ with respect to molecular alterations compared with noncecal proximal colon adenocarcinomas and that cecal tumor site may be a prognostically relevant variable. We compared molecular alterations, histopathologic features, and disease-specific survival in a series of 328 colonic adenocarcinomas identified over a 2-year period and stratified by tumor location (cecum, right colon, and left colon). Overall, cecal adenocarcinomas demonstrated the highest frequency of molecular abnormalities with 74% harboring either a KRAS exon 2 or 3 mutation, a BRAF mutation, or DNA mismatch repair protein deficiency. KRAS mutations were more frequently seen in the cecum compared with all other tumor sites (P = 0.03). KRAS mutations were identified in 46% of cecal adenocarcinomas compared with only 25% of adenocarcinomas of the right colon (P = 0.004). Cecal adenocarcinomas more frequently displayed adverse histopathologic features, in particular high tumor budding (31%), compared with tumors of the right colon (18%; P = 0.04) and tumors of the left colon (17%; P = 0.02). Overall stage was the most important independent predictor of disease-specific survival in the multivariable analysis; however, cecal tumor site and high tumor budding were also predictive of poor survival, particularly in patients with stage III or IV tumors. In conclusion, cecal adenocarcinomas are characterized by a high frequency of KRAS mutations compared with noncecal right colon tumors, frequently display high tumor budding, and may be a prognostically relevant variable, particularly in patients with stage III or IV disease.