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.
First Department of Pathology, Niigata University School of Medicine, Japan.
M
M
Kobayashi
H
H
Watanabe
Y
Y
Ajioka
T
T
Honma
H
H
Asakura
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000236:Adenoma / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007417:Intestinal Polyps / Q000235:genetics; D019394:Ki-67 Antigen / Q000032:analysis; D008940:Mitotic Index / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction
D019394:Ki-67 Antigen