Effect of K-ras mutation on morphogenesis of colorectal adenomas and early cancers: relationship to distribution of proliferating cells.

The authors evaluated the association of the K-ras mutation with the distribution of proliferating cells and the macroscopic appearance of colorectal tumors. A total of 122 colorectal adenomas and 96 early cancers were classified macroscopically as follows: (1) polypoid, exceeding 3 mm in height; (2) flat or hemispherically elevated 3 mm or less; and (3) depressed. The intramucosal areas of these tumors were examined by Ki-67 immunostaining and nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect proliferating cells and the K-ras codon 12 mutation. The distribution pattern of the Ki-67-positive cells was of two types: diffuse (D), being positive throughout the crypts, and superficial (S), being positive mainly in the superficial areas of the crypts. The K-ras mutation and the D type distribution of the Ki-67-positive cells were significantly less common (P < .005) in the nonpolypoid, depressed, or elevated tumors versus the polypoid tumors. The incidence of the K-ras mutation was significantly (P < .0001) associated with the D type distribution. The K-ras mutation may involve a disorder of cell proliferation that leads to the polypoid growth of colorectal tumors.