TUMOR-SUPPRESSOR ACTIVITY OF NEURAL CELL-ADHESION MOLECULE IN COLON-CARCINOMA

BACKGROUND AND AIMS: Neural Cell Adhesion Molecule (NCAM) is a well-ch aracterized member of the immunoglobin superfamily. The structure of N CAM is similar to the tumor suppressor Deleted in Colon Carcinoma (DCC ). NCAM has been found in some epithelial tissues and plays a role in tumorigenesis of some cancers. The purpose of the present study was to determine if NCAM is present in normal human colon. Once its presence was established, its function as a tumor suppressor was investigated. METHODS: Colon tumors and normal proximal margins were processed for reverse transcription-polymerase chain reaction (RT-PCR) of the NCAM-1 80 message. Immunohistochemistry of the tissue was performed to determ ine the distribution of NCAM. RESULTS: RT-PCR analysis demonstrated th e presence of the NCAM-180 kD isoform in normal colonic epithelia. Imm unohistochemistry showed NCAM on the basolateral surface of colonic ep ithelial cells of the villous tips. Tumors from 15 patients followed u p for 4 years were studied. All seven tumors expressing NCAM-180 were from patients having a benign clinical course. Seven of eight tumors t hat lacked NCAM-180 were associated with aggressive clinical behaviors (presenting with obstruction, perforation or metastatic disease, or p atient death within 18 months of presentation). The sole exception was in a villous adenoma excised from a patient who has had multiply recu rrent polyps on follow-up. CONCLUSION: We conclude that like DCC, NCAM is an important colonic adhesion molecule that functions as a tumor s uppressor. (C) 1997 by Excerpta Medica, Inc.