Stages of neoplastic transformation of human breast tissue as monitored by dissolution of basement membrane components. An immunoperoxidase study.

Two constituents of basement membrane, type IV collagen and laminin, were studied by immunoperoxidase methods in a group of breast lesions, exhibiting a range of neoplastic transformation. In normal breast, fibroadenoma, sclerosing adenosis, intraductal hyperplasia, and intraductal carcinoma there was intact basement membrane surrounding the ducts and lobules, as evidenced by an extracellular linear staining pattern with antibodies to type IV collagen and laminin. In intraductal carcinoma with microinvasion, there was fragmentation and absence of the basement membrane at the areas of microinvasion. Infiltrating carcinoma and metastatic breast carcinoma were usually devoid of surrounding extracellular basement membrane containing type IV collagen and laminin. However, a few well-differentiated carcinomas showed scattered extracellular deposits of this matrix material. Individual metastatic carcinoma cells, such as those in lymph nodes, contained intense cytoplasmic immunoreactivity with these antibodies. These results support the concept of basement membrane degradation associated with invasion. Furthermore, at least some metastatic tumor cells retain the ability to synthesize laminin and type IV collagen, but do not exhibit an extracellular basement membrane. This may mean that the metastatic cells are degrading and/or failing to deposit the extracellular matrix.