| Theme |
Aiming at the future of depressed type of lesion in early colorectal cancer |
| Title |
Frequent involvement of Ras-signalling pathways in both polypoid-type and flat-type early-stage colorectal cancers |
| Author |
Hiroshi Noda |
Department of Surgery, Saitama Medical Center, Jichi Medical University |
| Author |
Yoshio Miki |
Department of Molecular Diagnosis, Japanese Foundation for Cancer Research |
| Author |
Fumio Konishi |
Department of Surgery, Saitama Medical Center, Jichi Medical University |
| [ Summary ] |
The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways. However, the roles of their aberrations in connection with colorectal carcinogenesis remains unclear. The authors studied mutations in the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously exhibited any combination oi K-ras mutations BRAF mutations, or RASSF1A promoter methylation. Three of the 73 tumors (4.1 %) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenomas or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4 %), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades. |