Overexpression of SAP-1, a transmembrane-type protein tyrosine phosphatase, in human colorectal cancers.

SAP-1 is a human transmembrane-type protein tyrosine phosphatase that is abundant in colon and pancreatic cancer cell lines. The expression of SAP-1 in surgically excised human colorectal cancer specimens has now been investigated by immunohistochemical staining and in situ hybridization. Normal colon tissue or adenomas with mild dysplasia showed no detectable expression of SAP-1. In contrast, 2 of 17 adenomas with moderate or severe dysplasia and 19 of 48 (40%) adenocarcinomas expressed SAP-1, SAP-1 was localized predominantly to the apical surface of colonic cells in adenoma tissue showing moderate dysplasia, but it was also observed in the cytoplasm and at the basal surface of both adenoma cells showing severe dysplasia and adenocarcinoma cells. In situ hybridization with a SAP-1 antisense RNA probe detected SAP-1 mRNA in 6 of 9 colorectal cancers, but not in the surrounding mesenchymal tissue or normal mucosa. Sequencing of the K-RAS gene revealed that 10 of 15 (67%) SAP-1-positive cancers contained a mutation in codon 12. The serum concentration of carcinoembryonic antigen was normal in approximately half of the patients with SAP-1-positive colorectal cancers. These results suggest that SAP-1 is frequently overexpressed in human colorectal cancers and that such overexpression may occur relatively late in the adenoma-carcinoma sequence.