Immunohistologic analysis of invasive phenotype in breast carcinoma. A clinicopathologic study

Acetone-fixed, cryostat sections of 81 snap-frozen invasive breast carcinomas were immunostained with monoclonal antibodies to Cathepsin D (CD), a protease believed to mediate extracellular matrix dissolution, and Type IV collagen, a constituent of basal lamina (BL). Most cases (48/81, 53%) exhibited focal, patchy BL distribution (1+) around tumor cell nests, although subsets with diffuse continuous (2+) peritumoral sheets (15/81, 19%) or near complete absence (0+, 23/81, 28%) were also observed. Elaboration of BL was correlated with favorable morphologic differentiation (0+ BL-57% poorly differentiated vs. 2+ BL-13% poorly differentiated, p = .01), absence of nodal or systemic metastases (0+ BL-78% metastatic vs. 2+ BL-40% metastatic, p = .02), and improved disease-free survival (0+ BL-63% recurred vs. 2+ BL-20% recurred, p = .05). In addition, neoplastic cells expressed CD more frequently in tumors which lacked detectable BL synthesis (0+ BL-91% CD+ vs. 2+ BL-57% CD+, p = .03). The observed relationships between morphologic growth pattern, BL synthesis and CD expression imply conventional grading in large parts reflects activity or extent of host tissue invasion by a given neoplasm. Widespread but heterogeneous distribution of BL in breast tumors also suggests partial equilibrium between neoplastic and host tissues in most cases.