The hyperplasia-to-carcinoma sequence in the breast. Immunohistochemical-histologic correlations

Breast cancer is probably the result of a series of genetic events, each with its own histopathologic correlate in the hyperplasia to carcinoma sequence. The expression of breast cancer markers in hyperplasia and tumors are well known, but few studies have investigated their sequential expression among hyperplastic and cancerous lesions within the same breast. Using breast tissue obtained from a single procedure, we correlated the immunohistochemical expression of several breast cancer markers with the histopathologic stage of proliferative breast disease. We selected 14 cases in which various degrees of hyperplasia coexisted with carcinoma. Serial sections were reacted with antibodies to DF3, c-erbB-2, p53 (DO7 and CM1), B72.3, and cyclin D1. We found that within an individual breast, the number of breast cancer markers expressed increased with progression from hyperplasia to atypical hyperplasia to carcinoma. Cytoplasmic DF3 was first expressed at the level of simple hyperplasia, followed by c-erbB-2 in atypical hyperplasia. Overexpression of p53 was confined to carcinomas, and thus appeared to be a late event. B72.3 was expressed in three carcinomas and in one atypical hyperplasia, although the associated carcinoma was negative. Carcinomas that expressed cytoplasmic DF3 and c-erbB-2 were associated with atypical hyperplasias that also expressed cytoplasmic DF3 and c-erbB-2, with one and two exceptions, respectively. No specific cyclin D1 staining pattern was observed.