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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Wenbin Li, Tian Qiu, Wenxue Zhi, Susheng Shi, Shuangmei Zou, Yun Ling, Ling Shan, Jianming Ying, Ning Lu

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

KRAS 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 BRAF V600E mutation tests were performed in 762 primary tumors from a consecutive cohort study of Chinese CRC patients.

Methods

DNA 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.

Results

Mutations of KRAS (34.8%) and BRAF V600E (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.

Conclusions

In summary, KRAS codon 12 mutation, but not codon 13 mutation, is associated with lymph node metastasis and higher tumor stages.
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Metadata
Title
Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages
Authors
Wenbin Li
Tian Qiu
Wenxue Zhi
Susheng Shi
Shuangmei Zou
Yun Ling
Ling Shan
Jianming Ying
Ning Lu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1345-3

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