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bcl-2 and p53 Oncoprotein Expression during Colorectal Tumorigenesis

Departments of Gastrointestinal Medical Oncology and Digestive Diseases [F. S., B. L.] and Biomathematics [J. J. L.] and the Divisions of Pathology [K. R. C.] and Veterinary Medicine and Surgery [L. C. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.

¹ To whom requests for reprints should be addressed, at Department of Gastrointestinal Oncology and Digestive Diseases, 1515 Holcombe Blvd., Box 78, Houston, TX 77030.

Received 9/ 6/94. Accepted 12/ 2/94.

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