Review
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2012; 18(37): 5171-5180
Published online Oct 7, 2012. doi: 10.3748/wjg.v18.i37.5171
KRAS mutation testing in metastatic colorectal cancer
Cong Tan, Xiang Du
Cong Tan, Xiang Du, Department of Oncology, Shanghai Medical School, Fudan University, Shanghai 200032, China
Cong Tan, Xiang Du, Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Author contributions: Tan C wrote this manuscript; and Du X significantly designed and revised the manuscript, and approved the final version.
Supported by Science and Technology Commission of Shanghai Municipality, No. 10DJ1400501
Correspondence to: Xiang Du, MD, PhD, Department of Pathology, Shanghai Cancer Center, Fudan University, 270 Dong An Road, Shanghai 200032, China. dx2008cn@yahoo.com.cn
Telephone: +86-21-64175590 Fax: +86-21-64170067
Received: February 16, 2012
Revised: June 6, 2012
Accepted: August 4, 2012
Published online: October 7, 2012
Abstract

The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies. Therefore, determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers. Currently, a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however, several challenges remain related to standardized and uniform testing, including the selection of tumor samples, tumor sample processing and optimal testing methods. Moreover, new testing strategies, in combination with the mutation analysis of BRAF, PIK3CA and loss of PTEN proposed by many researchers and pathologists, should be promoted. In addition, we recommend that microsatellite instability, a prognostic factor, be added to the abovementioned concomitant analysis. This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing. This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.

Keywords: KRAS; Epidermal growth factor receptor; Metastatic colorectal cancer; Testing status; Biomarker