Extracellular matrix proteins and their receptors in the normal, hyperplastic and neoplastic breast

Abstract

We studied by immunohistochemistry, the distribution of tenascin (Ten), cellular fibronectin (cFn), laminin and certain pertinent extracellular matrix protein receptors in normal human female breast, variants of fibrocystic disease (FCD), benign tumors, and ductal and lobular carcinomas. Monoclonal antibodies (mAb) to Ten, extradomain A containing cFn (EDAcFn), A and B chains of laminin, and beta-1 (β-1) and different α subunits of integrins were used.

In in-situ ductal and lobular carcinomas, laminin staining had focal gaps, Ten-immunoreactivity displayed periductal or periacinar bands, and cFn showed broad and intense periductal staining; strong reactions for β-1 and α-6 were noted in the basal cytoplasm of non-neoplastic myoepithelial cells while few tumor cells stained weakly. In infiltrating ductal and lobular carcinomas (IDC, ILC), laminin reactivity was weak, uneven or absent around neoplastic clusters whereas stromal staining for Ten and cFn was extensive and strong. In most IDC, moderate β-1 and α-6 staining involved variable subpopulations; one mucinous carcinoma stained strongly and diffusely. In 20–40% of cells in ILC, β-1 and α-6 were localized in delicate, ramified cytoplasmic processes. Indirect immunofluorescence studies with mAbs to other α-integrin subunits suggest that in various breast carcinomas only α-3 is expressed in tumor cells and that the vessels contained α-1 integrin.

As compared with the normal breast, FCD and benign tumors, reactivity for Ten and cFn is increased in breast carcinomas while laminin is attenuated and decreased or absent; yet, Ten cannot be regarded as a carcinoma marker since it can be detected in benign tumors, FCD, and even in the normal breast. Reactivity for β-1 and α-6 integrin subunits is decreased in all breast carcinomas; however, the comparatively strong and distinctly localized reactions noted in lobular vs ductal carcinomas may well reflect biological and clinical differences between these two main breast carcinoma phenotypes.