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

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. (2013) Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features. Modern Pathology, 26 6: 825-834. doi:10.1038/modpathol.2012.240


Author 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.
Buchanan, Daniel D.
Title Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features
Journal name Modern Pathology   Check publisher's open access policy
ISSN 0893-3952
1530-0285
Publication date 2013-06
Sub-type Article (original research)
DOI 10.1038/modpathol.2012.240
Open Access Status Not Open Access
Volume 26
Issue 6
Start page 825
End page 834
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing
Collection year 2014
Language eng
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. 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 (P<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%; P<0.001), presence of a contiguous polyp (38 vs 22%; P<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.
Keyword BRAF mutation
Colorectal cancer
Colorectal polyp
KRAS mutation
MGMT
Molecular pathology
Survival analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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