IMMUNOHISTOCHEMICAL EXPRESSION OF THE MUTANT P53 PROTEIN AND NUCLEAR-DNA CONTENT DURING THE TRANSITION FROM BENIGN TO MALIGNANT BREAST DISEASE

Immunohistochemical expression of the cellular phosphoprotein p53 was investigated in archival, formalin-fixed, and paraffin-embedded surgic al breast tissue specimens from 543 patients using the polyclonal anti body CM-1. Cytometric DNA assessments were performed on histopathologi cally or cytopathologically identified cell nuclei using image analysi s. The series included five samples of normal resting breast parenchym a, 35 benign lesions including benign tumors, 54 hyperplastic lesions with and without atypia, 109 carcinomas in situ, and 340 invasive aden ocarcinomas. In 56 of the latter cases specimens from corresponding ly mph node metastases also were investigated. Mutant p53 protein express ion was absent in normal resting parenchyma and in benign lesions, inc luding benign tumors and epithelial hyperplasias. However, 14 of the 5 4 hyperplasias (26%) were found to be of DNA aneuploid type. Thirteen of 109 (12%) carcinomas in situ and 79 of 340 (23%) invasive neoplasms expressed the mutant p53 protein. Eight of nine (89%) p53 immunoreact ive carcinomas in situ and 62 of 78 (80%) invasive carcinomas with p53 expression were DNA. aneuploid. In invasive carcinomas p53 expression was absent in well differentiated neoplasms. In contrast, 58 of 158 ( 37%) poorly differentiated invasive carcinomas immunoreacted. Intraduc tal carcinomas of comedo type and poorly differentiated invasive carci nomas of comedo type expressed the mutant p53 protein in seven of 18 c ases (39%) and in 14 of 22 cases (64%), respectively. The staining beh avior of lymph node metastases was the same as that of the correspondi ng primary tumors. The present findings suggest that chromosomal alter ations as indicated by DNA aneuploidy occur in precancerous lesions. H owever, immunohistochemically detectable accumulation of mutant p53 pr otein cannot be observed before the carcinoma in situ phase. The highe st levels of p53 protein overexpression are found in invasive carcinom as and are closely associated with aneuploidy and poor differentiation . However, p53 overexpression apparently does not increase further dur ing; the tumor spread to lymph nodes. (C) 1994 by W.B. Saunders Compan y