BCL-2 AND P53 ONCOPROTEIN EXPRESSION DURING COLORECTAL TUMORIGENESIS

Apoptosis or programmed cell death represents a mechanism by which cel ls possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and prop agation of cells containing genetic alterations. To determine if and w hen the bcl-2 gene is activated during colorectal tumorigenesis and it s relationship to p53, we analyzed normal mucosa, hyperplastic and dys plastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restric ted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dyspl astic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers ma y regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bel-2-positive cells were significantly more likel y to have low rates of spontaneous apoptosis, as determined histologic ally, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorect al tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.