Cell death in colorectal polyps as evaluated by in situ 3'-tailing reaction and its relationship to BCL-2 expression

Colorectal polyps were analyzed from the standpoint of cell death by using the in situ 3'-tailing reaction (ISTR), which identifies cell death-associated DNA double strand breaks, and immunohistochemistry for bcl-2 oncoprotein (BCL-2) and for Ki-67. There were few ISTR-positive cells in the non-neoplastic glands, whereas 38% of non-neoplastic mucosa just adjacent to the adenoma had many labeled nuclei, suggestive of cell death associated with replacement by tumor. The neoplastic glands contained variable number of ISTR-positive nuclei, mostly showing the morphological feature of apoptotic bodies. In the representative glands with the most prominent ISTR-labeling, their indices did not have a significant relationship to the grade of atypia, to the proliferative activity (Ki-67 labeling indices) of neoplastic glands, or to BCL-2 stainability. In each case, however, the neoplastic glands with no or few ISTR-labeled nuclei tended to express BCL-2 intensely, and all lesions of adenoma or carcinoma with more than 15% of ISTR-labeling indices showed weak BCL-2 immunoreactivity. In general, BCL-2 expression was significantly stronger in the adenoma than in non-neoplastic mucosa and carcinoma, although there was no significant difference of ISTR-labeling between adenoma and carcinoma. These results indicate that cell death in colorectal neoplastic polyps does not have a significant influence on their growth rate, and that BCL-2 plays some role, at least in part, in the regulation of apoptosis.