DETECTION OF ONCOGENE MUTATION FROM NEOPLASTIC COLONIC CELLS EXFOLIATED IN FECES

PURPOSE: Best chances of a cure from colorectal cancer are obtained be fore metastatic spread. Lack of specific tests allowing early diagnosi s of the tumor accounts for investigation of gene alterations involved in carcinogenesis by a noninvasive method. in the present study, K-ra s codons 12 and 13 mutations were studied in neoplastic cells shed fro m the bowel into the stool and those contained in the tumor and normal mucosa. Moreover, healthy patients and a few others with precancerous conditions mere examined. METHODS: Stool, tumor, and mucosa samples w ere taken from 25 patients with colorectal adenocarcinoma. Stool and m ucosa samples were obtained from 11 healthy patients, and stool, patho logic bowel tissue, and normal mucosa samples were obtained from 3 pat ients with adenoma (1) or ulcerative colitis (2). Polymerase chain rea ction amplification and restriction enzyme analysis were performed. RE SULTS: K-ras codon 12 mutations were detected in both tumor and stool samples of 10 cancer patients, and no gene alterations were observed i n 14 patients. In one patient with a tumor, a mutation was shown in on ly the tumor tissue. The agreement rate in tumor and stool analysis wa s 96 percent. A normal pattern of K-ras codons 12 and 13 was observed in the bowel mucosa. Ail stool and mucosa samples from healthy patient s were not altered in K-ras. Agreement was registered between samples taken from patients with preneoplastic lesions. CONCLUSIONS: These pre liminary findings show a high rate of accuracy in the investigation of K-ras alterations in the colorectal cells shed into the feces, sugges ting that such an approach could be used to study other gene alteratio ns and, prospectively, to identify early colorectal cancers.