151. Colorectal carcinomas with KRASmutation are associated with distinctive morphological and molecular features
- Author
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Rosty, Christophe, Young, Joanne P, Walsh, Michael D, Clendenning, Mark, Walters, Rhiannon J, Pearson, Sally, Pavluk, Erika, Nagler, Belinda, Pakenas, David, Jass, Jeremy R, Jenkins, Mark A, Win, Aung Ko, Southey, Melissa C, Parry, Susan, Hopper, John L, Giles, Graham G, Williamson, Elizabeth, English, Dallas R, and Buchanan, Daniel D
- Abstract
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. KRASmutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study. O6-methylguanine DNA methyltransferase(MGMT) status was assessed using both immunohistochemistry and MethyLight techniques. Microsatellite instability (MSI) phenotype and BRAFV600E mutation status were derived from earlier studies. Mutation in KRAScodon 12 or codon 13 was present in 28% of colorectal carcinomas. Compared with KRASwild-type carcinomas, KRAS-mutated carcinomas were more frequently observed in contiguity with a residual polyp (38 vs21%; P<0.001), demonstrated mucinous differentiation (46 vs31%; P=0.001) and were associated with different MSI status (P<0.001) and with MGMTmethylation (47 vs21%; P=0.001). Compared with tumors demonstrating neither BRAFnor KRASmutation, KRAS-mutated carcinomas showed more frequent location in the proximal colon (41 vs27%; P=0.001), mucinous differentiation (46 vs25%; P<0.001), presence of a contiguous polyp (38 vs22%; P<0.001), MGMTmethylation (47 vs26%; P=0.01) and loss of MGMT immunohistochemical expression (27 vs19%; 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 vs15%; P=0.02). No difference in overall survival was observed in patients according to their tumor KRASmutation 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 BRAFnor KRASmutation.
- Published
- 2013
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