Is Ki-67 a better proliferative marker in the colon than proliferating cell nuclear antigen?

Endogenous markers of proliferating cells have increasingly supplanted the use of incubation of biopsy tissues in vitro with tritiated thymidine or with bromodeoxyuridine, thus avoiding the potential variation resulting from the incubation procedure. Antibodies to proliferating cell nuclear antigen (PCNA) such as PC10 have been promoted as optimal for this purpose, although considerable variation in colonic proliferating cells with this antibody has been reported. We have compared the detection of colonic proliferating cells in normal mucosa and adenomata using the PC10 monoclonal antibody (mAb) to PCNA and the Mib-1 mAb to Ki-67 in formalin-fixed tissues using antigen retrieval solutions with microwaving. The PC10 antibody showed variable immunostaining of proliferating and nonproliferating cells with minor changes in primary antibody concentration or microwave conditions and between normal and adenomatous tissue. In contrast, Mib-1 immunostaining was quite constant with differing antigen retrieval and antibody conditions and similar staining of proliferating cells in colonic adenomas. Some loss of immunoreactivity occurred if the cut sections were not immunostained within approximately 1 week. These data suggest that whereas PCNA immunohistochemistry is satisfactory when carefully controlled in large chemopreventive studies, the Mib-1 mAb to Ki-67 is superior to PCNA antibodies in immunostaining proliferating cells in the formalin-fixed human colon.

Inward growth of colonic adenomatous polyps.

BACKGROUND & AIMS: Most colon cancers arise from polypoid adenomas, but how these benign lesions develop into malignant neoplasms is not understood. This study examined the migration of epithelial cells within human adenomatous polyps by determining the distribution of proliferating and apoptotic cells and immunoreactivity to transforming growth factor beta (TGF-beta). METHODS: Sections of surgically resected normal (n = 10) and adenomatous (n = 22) formalin-fixed tissue were examined for proliferating cells and TGF-beta isoenzymes 1-3 by immunohistochemistry and apoptotic cells by terminal deoxyuridine nick end-labeling. RESULTS: The distribution of proliferating, apoptotic, and TGF-beta immunoreactive cells was strikingly reversed in adenomatous polyps compared with normal mucosa. Proliferating cells were located in the base of normal colonic crypts and TGF-beta immunoreactive and apoptotic cells near or at the luminal surface, corresponding to the normal migration of colonocytes. In adenomas, increased numbers of proliferating cells were mainly located at the luminal surface and TGF-beta immunoreactive and apoptotic cells were located principally at the crypt base. CONCLUSIONS: This distribution suggests that cell migration in adenomas is not toward the lumen but instead inward toward the polyp base.