Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma.

Neural Cell Adhesion Molecule (NCAM) is a well-characterized member of the immunoglobin superfamily. The structure of NCAM 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. Colon tumors and normal proximal margins were processed for reverse transcription-polymerase chain reaction (RT-PCR) of the NCAM-180 message. Immunohistochemistry of the tissue was performed to determine the distribution of NCAM. RT-PCR analysis demonstrated the presence of the NCAM-180 kD isoform in normal colonic epithelia. Immunohistochemistry showed NCAM on the basolateral surface of colonic epithelial cells of the villous tips. Tumors from 15 patients followed up for 4 years were studied. All seven tumors expressing NCAM-180 were from patients having a benign clinical course. Seven of eight tumors that lacked NCAM-180 were associated with aggressive clinical behaviors (presenting with obstruction, perforation or metastatic disease, or patient death within 18 months of presentation). The sole exception was in a villous adenoma excised from a patient who has had multiply recurrent polyps on follow-up. We conclude that like DCC, NCAM is an important colonic adhesion molecule that functions as a tumor suppressor.