Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

Rosty C, Young JP, Walsh MD, Clendenning M, Walters RJ, Pearson S, Pavluk E, Nagler B, Pakenas D, Jass JR, Jenkins MA, Win AK, Southey MC, Parry S, Hopper JL, Giles GG, Williamson E, English DR, Buchanan DD (2013) Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26:825-834

KRAS-mutated carcinomas comprise 35-40% of all colorectal carcinomas but little is known about their characteristics. The aim of this study was to examine the pathological and molecular features of KRAS-mutated colorectal carcinomas and to compare them with other carcinoma subgroups. KRAS mutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study. O(6)-methylguanine DNA methyltransferase (MGMT) status was assessed using both immunohistochemistry and MethyLight techniques. Microsatellite instability (MSI) phenotype and BRAF V600E mutation status were derived from earlier studies. Mutation in KRAS codon 12 or codon 13 was present in 28% of colorectal carcinomas. Compared with KRAS wild-type carcinomas, KRAS-mutated carcinomas were more frequently observed in contiguity with a residual polyp (38 vs 21%; P<0.001), demonstrated="" mucinous="" differentiation="" (46="" vs="" 31%;="" p="0.001)" and="" were="" associated="" with="" different="" msi="" status=""><0.001) and="" with="" mgmt="" methylation="" (47="" vs="" 21%;="" p="0.001)." compared="" with="" tumors="" demonstrating="" neither="" braf="" nor="" kras="" mutation,="" kras-mutated="" carcinomas="" showed="" more="" frequent="" location="" in="" the="" proximal="" colon="" (41="" vs="" 27%;="" p="0.001)," mucinous="" differentiation="" (46="" vs="" 25%;=""><0.001), presence="" of="" a="" contiguous="" polyp="" (38="" vs="" 22%;=""><0.001), mgmt="" methylation="" (47="" vs="" 26%;="" p="0.01)" and="" loss="" of="" mgmt="" immunohistochemical="" expression="" (27="" vs="" 19%;="" p="0.02)." kras-mutated="" carcinomas="" were="" distributed="" in="" a="" bimodal="" pattern="" along="" the="" proximal-distal="" axis="" of="" the="" colorectum.="" compared="" with="" male="" subjects,="" female="" subjects="" were="" more="" likely="" to="" have="" kras-mutated="" carcinoma="" in="" the="" transverse="" colon="" and="" descending="" colon="" (39="" vs="" 15%;="" p="0.02)." no="" difference="" in="" overall="" survival="" was="" observed="" in="" patients="" according="" to="" their="" tumor="" kras="" mutation="" status.="" in="" summary,="" kras-mutated="" carcinomas="" frequently="" develop="" in="" contiguity="" with="" a="" residual="" polyp="" and="" show="" molecular="" features="" distinct="" from="" other="" colorectal="" carcinomas,="" in="" particular="" from="" tumors="" with="" neither="" braf="" nor="" kras="" mutation.modern="" pathology="" advance="" online="" publication,="" 25="" january="" 2013;="">