RAS GENE ACTIVATION IN HUMAN SMALL INTESTINAL TUMORS

Expression of the ras oncoprotein in thirteen human small intestinal tumors was investigated employing an immunohistochemical technique. The level of ras p21 was analysed using the monoclonal antibody Y13-259 and the biotin-streptavidin-peroxidace-DAB technique. Nine out of thirteen tumors including one hyperplastic - metaplastic polyp, one adenomatous and papillary polyp of the duodenum, one adenomatous polyp, one leiomyoma, one carcinoid, one lymphoma, one angiosarcoma of the jejunum, one leiomyosarcoma and one metastatic adenocarcinoma of the colon, were found to ''press the ras p21 oncoprotein at elevated levels, as compared to adjacent normal tissue. Whereas in one Brunner's gland adenoma of the duodenum, one neurilemoma, one adenocarcinoma of the small intestine and one metastatic adenocarcinoma of the colon expression of ras p21 was not elevated. The detection of H-ras mutations in codon 12 and K-ras mutations in codons 12 and 13 was also examined using the polymerase chain reaction technique. Four out of the thirteen small intestinal tumors examined possessed mutations of the H-ras gene in codon 12. These included the following, tumors: one Brunner's gland adenoma of the duodenum, one lymphoma, one leiomyo-sarcoma and one metastatic adenocarcinoma of the colon. This is the first demonstration of ras mutations in small intestinal tumors. None of the tumors had mutations in K-ras codons 12 or 13 (Gly-->Asp) It is suggested that the ras p21 oncoprotein may be involved in the pathogenesis and H-ras mutations and be a molecular genetic marker in small intestinal tumors.