CORRELATION BETWEEN THE EXPRESSION OF APOPTOSIS-RELATED BCL-2 AND P53ONCOPROTEINS AND THE CARCINOGENESIS AND PROGRESSION OF BREAST CARCINOMAS

The proto-oncogene bcl-2, which is implicated in the regulation of cel l death by inhibiting apoptosis, is reported to be expressed in breast tissues. The wild-type p53 has been shown to induce apoptosis, which can be inhibited by bcl-2 expression, However, the role of bcl-2 and p 53 expression in breast carcinogenesis has not been clarified. The pur pose of this study was to evaluate bcl-2 and p53 expression in normal breast epithelia cells, as well as in intraductal and invasive cancero us lesions of breast cancer tissue using an immunohistochemical method and to clarify their role in the development of breast cancer. The nu clear accumulation of p53 was also evaluated by quantitative image ana lysis. Expression of bcl-2 was found in 79 of 82 (96%) normal ductal e pithelial cells, in 50 of 63 (79%) intraductal carcinomas, and in 62 o f 137 (45%) invasive carcinomas, respectively. Higher bcl-2 expression was observed in normal epithelial cells than in intraductal and invas ive cancerous cells (P < 0.0001). Furthermore, bcl-2 positivity in int raductal lesions was significantly higher than in invasive cancerous l esions (P < 0.05). No p53 nuclear accumulation was observed in normal breast epithelial cells. Fifteen of 63 (23.8%) intraductal cancerous l esions and 41 of 137 (30%) invasive cancerous lesions were positive fo r p53 expression. An inverse relationship was shown between bcl-2 and p53 expression in invasive carcinomas. We demonstrated that bcl-2 expr ession exists in most of normal ductal epithelial cells and gradually decreases during the development of breast cancer, i.e., from a normal epithelium to intraductal carcinoma, and from intraductal to invasive carcinoma, and that p53 expression may occur early in breast cancer d evelopment and increases during progression.