EXPRESSION OF PARATHYROID-LIKE PROTEIN IN NORMAL, PROLIFERATIVE, AND NEOPLASTIC HUMAN BREAST TISSUES

Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally ho mologous to parathyroid hormone. Immunohistochemical studies have iden tified amino-terminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in si tu hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyc lonal antibody that recognizes epitopes within the middle and carboxyl -terminal domains of PLP, immunoreactive protein was detected within t he cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplas mic staining was increased in association with lactation, adenosis, an d simple or atypical ductal hyperplasia and decreased in atrophic lobu les. Cytoplasmic reactivity was also observed in 69% (56 of 81) of bre ast adenocarcinomas. Expression of immunoreactive PLP was inversely co rrelated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in P LP-positive normal and neoplastic breast tissue. Interestingly, tumor- associated calcifications were identified in 43% of PLP-positive carci nomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our res ults suggest that PLP plays some role in the normal differentiated fun ction of mammary epithelial cells and are consistent with the hypothes is that expression of this protein influences local calcium metabolism .