IMMUNODETECTION OF P53 PROTEIN IN NONINVASIVE EPITHELIAL PROLIFERATIVE BREAST DISEASE

Accumulation of the immunoreactive protein product of the p53 tumor su ppressor gene has been previously detected in approximately 30-40% of all invasive carcinomas of the breast, and immunohistochemical detecti on of p53 accumulation in the nuclei of breast carcinoma cells has bee n forwarded as a prognostic indicator. Limited data exist on the incid ence of p53 protein accumulation in various histologic types of noninv asive epithelial proliferations in the breast. In this investigation, the incidence of immunoreactive nuclear p53 protein was assessed by im munohistochemical analysis using monoclonal antibody PAb 1801 on forma lin-fixed, paraffin-embedded tissue sections of histologically normal mammary epithelium (n = 42), epithelial hyperplasia (n = 33), and pure carcinoma in situ (n = 52). p53 protein accumulation was not detectab le in normal mammary epithelium, epithelial hyperplasia of the usual t ype, atypical lobular hyperplasia, or atypical ductal hyperplasia. Imm unoreactive p53 was identified in nuclei of 7/52 (13.5% of) cases of c arcinoma in situ, with 5 of these 7 cases (71%) classified as classica l comedo type of ductal carcinoma in situ. Immunodetectable p53 protei n accumulation was uncommon in other histologic types of carcinoma in situ, with these incidence levels: 1/11 (9.1% of) cribriform ductal ca rcinoma in situ cases, 1/7 (14.3% of) micropapillary ductal carcinoma in situ cases, 0/4 solid ductal carcinoma in situ cases, 0/6 mixed pat tern ductal carcinoma in situ cases, and 0/5 lobular carcinoma in situ cases. The two cases of ductal carcinoma in situ with predominant cri briform and micropapillary architectural growth patterns and immunodet ectable p53 had comedo features. In conclusion, the earliest morpholog ic stage of breast epithelial proliferation with p53 protein accumulat ion is at the level of ductal carcinoma in situ, with the comedo type of ductal carcinoma in situ comprising the majority of cases of carcin oma in situ with p53 protein accumulation.