Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages

BMC Cancer

Research Article

Ling Shan¹  Wenxue Zhi¹  Shuangmei Zou¹  Yun Ling¹  Jianming Ying¹  Wenbin Li¹  Susheng Shi¹  Tian Qiu¹  Ning Lu¹ 

[1] Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China;

关键词: KRAS;    BRAF;    Colorectal cancer;    Codon 12 and 13;    DNA mismatch repair;   

DOI  :  10.1186/s12885-015-1345-3

 received in 2014-12-29, accepted in 2015-04-22,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundKRAS mutation occurs in 35%-40% of colorectal cancer (CRC). The aim of our study was to evaluate the pathological and molecular features of specific KRAS mutated colorectal carcinomas. KRAS and BRAFV600E mutation tests were performed in 762 primary tumors from a consecutive cohort study of Chinese CRC patients.MethodsDNA mismatch repair (MMR) status was determined by immunohistochemistry (IHC) staining. Assessment of KRAS and BRAF V600E mutational status was performed using a multiplex allele-specific PCR-based assay.ResultsMutations of KRAS (34.8%) and BRAFV600E (3.1%) were nearly mutually exclusive. Both KRAS- and BRAF- mutated tumors were more likely to be located at proximal colon than wild-type (WT) carcinomas. KRAS-mutated carcinomas were more frequently observed in female patients (47.5% vs 37.1%, p = 0.005) and mucinous differentiation (34.7% vs 24.8%, p = 0.004), but have no difference between lymph node (LN) metastases and among pTNM stages. Whereas, BRAF-mutated carcinomas more frequently demonstrated histologic features such as proximal location (60.9% vs 20.9%, p = 0.001), low-grade histology (43.5% vs 18.0%, p = 0.005), mucinous differentiation (69.6% vs 25.9%, p = 0.001) and deficient MMR (dMMR) (21.7% vs 7.6%, p = 0.03). In particular, KRAS codon 12 mutated carcinomas had increased lymph node metastasis (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.04 to 1.65; P = 0.02) and were more likely in higher disease stage (III-IV) than that of WT carcinomas (OR = 1.30; 95% CI = 1.03 to 1.64; P = 0.03). However, there were no significant differences in lymph node metastasis and disease stage between KRAS codon 13 mutated carcinoma and WT carcinoma patients.ConclusionsIn summary, KRAS codon 12 mutation, but not codon 13 mutation, is associated with lymph node metastasis and higher tumor stages.

【 授权许可】

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© Li et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.