IMMUNOHISTOCHEMICAL DETECTION OF TRUNCATED APC PROTEIN IN SPORADIC HUMAN COLORECTAL ADENOMAS AND ADENOCARCINOMAS

Mutations of the APC gene frequently occur in sporadic forms of colore ctal adenomas and adenocarcinomas. Phenotypically, the vast majority o f these mutations result in the truncation of the APC protein. To demo nstrate the defective APC gene product in human colorectal tumors, rab bit region-specific antisera raised against the APC protein of amino a cid sequences between 371 and 390 (SP1) and between 1821 and 1840 (SP3 ) were used to exhibit the truncated APC protein. In all, 86 lesions f rom 67 cases of sporadic adenoma and adenocarcinoma were examined; abn ormal staining patterns were distinguished in 43 lesions (50%); the in cidence of abnormalities was not significantly different between adeno mas and carcinomas. The majority, 75% exhibited epitopic change with t he SP1-positive and SP3-negative phenotype (type P1), and 25% exhibite d neither of these phenotypes (type P2). The staining pattern in all l esions was uniform, and studies of carcinomas arising in adenomas show ed the same pattern of staining. These findings supported the view tha t the APC lesion is a very early event in colorectal carcinogenesis, F urthermore, this simple immunohistochemical approach demonstrated that different adenomas from the same patient showed different staining pa tterns.