Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages.
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.
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. liwenbin9631@hotmail.com.
Wenbin
W
Li
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. qiutian1228@126.com.
Tian
T
Qiu
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. zhiwenxue303@sina.com.
Wenxue
W
Zhi
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. shishusheng@sina.com.
Susheng
S
Shi
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. smzou@hotmail.com.
Shuangmei
S
Zou
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. lingyun_1991@163.com.
Yun
Y
Ling
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. shanling0612@hotmail.com.
Ling
L
Shan
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. jmying@hotmail.com.
Jianming
J
Ying
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center, Beijing, China. nlu03@126.com.
Ning
N
Lu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins