IMMUNODETECTION OF P53 PROTEIN IN NONINVASIVE EPITHELIAL PROLIFERATIVE BREAST DISEASE

Accumulation of the immunoreactive protein product of the p53 tumor suppressor gene has been previously detected in approximately 30-40% of all invasive carcinomas of the breast, and immunohistochemical detection of p53 accumulation in the nuclei of breast carcinoma cells has been forwarded as a prognostic indicator. Limited data exist on the incidence of p53 protein accumulation in various histologic types of noninvasive epithelial proliferations in the breast. In this investigation, the incidence of immunoreactive nuclear p53 protein was assessed by immunohistochemical analysis using monoclonal antibody PAb 1801 on formalin-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 detectable in normal mammary epithelium, epithelial hyperplasia of the usual type, atypical lobular hyperplasia, or atypical ductal hyperplasia. Immunoreactive p53 was identified in nuclei of 7/52 (13.5% of) cases of carcinoma in situ, with 5 of these 7 cases (71%) classified as classical comedo type of ductal carcinoma in situ. Immunodetectable p53 protein accumulation was uncommon in other histologic types of carcinoma in situ, with these incidence levels: 1/11 (9.1% of) cribriform ductal carcinoma 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 pattern ductal carcinoma in situ cases, and 0/5 lobular carcinoma in situ cases. The two cases of ductal carcinoma in situ with predominant cribriform and micropapillary architectural growth patterns and immunodetectable p53 had comedo features. In conclusion, the earliest morphologic stage of breast epithelial proliferation with p53 protein accumulation is at the level of ductal carcinoma in situ, with the comedo type of ductal carcinoma in situ comprising the majority of cases of carcinoma in situ with p53 protein accumulation.