RANDOM NUCLEAR P53 OVEREXPRESSION PATTERN IN TAMOXIFEN-MEDIATED ENDOMETRIAL CARCINOMA

In a previous paper, we suggested that tamoxifen (TAM)-mediated endome trial carcinogenesis may not involve estrogenic pathways because of ra ndom estro en receptor positivity among endometrial carcinomas with an d without TAM treatment for breast cancer. DNA adduct formation (repor ted in rat liver and human endometrium) was considered to be a more pl ausible mechanism for TAM-mediated carcinogenesis. To examine the repo rted correlation between DNA adduct formation and p53, the present stu dy examined p53 expression in the endometrial carcinomas reported in t he previous study. Seven endometrial adenocarcinomas associated with l ong-term TAM treatment for breast carcinoma and 4 carcinomas without T AM treatment but with history of breast carcinoma were immunohistochem ically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and untrea ted patients with cancer. Thus, p53 overexpression in endometrial carc inomas occurring in patients with breast cancer seems to be not specif ic for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related pre ferentially to p53 gene alteration. Further studies are needed to unde rstand the precise mechanism(s) of the endometrial carcinogenesis.