Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer.
OBJECTIVE
Many investigators have reported flat and depressed lesions as a new type of precursor of colorectal cancer. In our previous study, we determined that mutations in the BRAF gene may contribute to colorectal carcinogenesis by inhibiting apoptosis. However, the relationship among BRAF mutations, morphology and apoptosis in early colorectal cancer has not been clear. Therefore, gene alternation, morphology, and apoptosis in early colorectal cancer were investigated.


METHODS
Forty-five flat and depressed early colorectal cancer samples and 43 polypoid early colorectal cancer samples were analyzed. Mutations in the BRAF gene and the K-ras gene were examined by direct sequence analysis, and proliferative activity and induction of apoptosis were evaluated using immunohistochemical examination. RESULTS FINDINGS: BRAF mutations were found in 5 (11.1%) of 45 flat and depressed early colorectal cancer samples. No BRAF alteration was found in polypoid early colorectal cancer samples. Mutations in the K-ras gene were detected in 13 (30.2%) of 43 polypoid early colorectal cancer samples. The rate of submucosal invasion of the samples with BRAF mutations was significantly higher than that of the samples with K-ras mutations (p<0.05).


CONCLUSIONS
BRAF and K-ras mutations were independent factors that influenced morphology in early colorectal cancer. In this study, the relationship between BRAF mutation and apoptosis is not so clear, but BRAF mutations and inhibition in apoptosis may play an important role in the developmental process of flat and depressed early colorectal cancer.
Yoshida
Shiei
S
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Ikehara
Nobunao
N
Aoyama
Nobuo
N
Shirasaka
Daisuke
D
Sakashita
Masanori
M
Semba
Shuho
S
Hasuo
Tadateru
T
Miki
Ikuya
I
Morita
Yoshinori
Y
Tamura
Takao
T
Azuma
Takeshi
T
Yokozaki
Hiroshi
H
Kasuga
Masato
M
D017209:Apoptosis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf