J.Jpn. Surg. Soc.. 94(12): 1249-1255, 1993

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Original article

CELL KINETICS OF COLORECTAL TUMORS WITH ASSESSMENT BY K-RAS MUTATION AND PCNA LABELING INDEX

K-ras mutations in colorectal tumors (53 carcinomas, 21 adenomas) were investigated using oligonucleotide probes specific for mutations at codon 12, 13, or 61 of the K-ras gene by polymerase chain reaction and oligonucleotide hybridization techniques, and the proliferative activities were assessed immunohistochemistrically by using anti-proliferating cell nuclear antigen (PCNA), counting PCNA labeling index (LI). Point mutations were observed 18.8% in the adenomas, 40.0% in the intramucosal carcinomas and 27.0% in the invasive carcinomas. Fewer incidences of K-ras mutations in the invasive carcinoma suggested carcinomas without K-ras mutation invade rapidly.
Clincopathologically, K-ras mutation-positive carcinomas tended to show the presence of venous invasion (p＜0.005). There were many distant metastases in the K-ras mutation-positive cases (p=0.07). Moreover, among adenocarcinomas a significant correlation was demonstrated between PCNA LI and the pattern of infiltrating growth (p＜0.05). Our data imply that the K-ras mutation gains access to invasion and metastasis, as well as the ras mutation occurs at the initiation of the carcinoma. The present data suggest that K-ras mutations in colorectal carcinomas are correlated with venous invasion, while cell proliferative activities are related to stromal invasion, and these factors are independent markers for invasion of colorectal carcinomas.

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