INTERACTION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR IN BREAST-CARCINOMA - AN IMMUNOHISTOLOGIC STUDY

Background. Interaction of transforming growth factor-alpha (TGF-alpha ) with its receptor, epidermal growth factor receptor (EGFR), has been implicated as an autoregulatory autocrine mechanism of breast epithel ial proliferation. Methods. To examine the interrelationship and clini cal relevance of TGF-alpha and EGFR in breast carcinoma, methanol-fixe d cryostat sections from 73 patients were immunostained with monoclona l antibodies to epidermal growth factor (EGF), EGFR, and TGF-alpha. Re sults. Neither EGFR nor TGF-alpha staining was diagnostic or specific for the detection of malignant neoplastic cells. Both exhibited staini ng along the basal lamina of most benign ducts and lobules. TGF-alpha staining was observed in neoplastic cells in 41% and in non-neoplastic cells (peritumoral stroma and benign duct/lobular epithelium) in 36% of patients. Staining for EGF and TGF-alpha failed to correlate with n ode status or grade; however, TGF-alpha negative tumors were more freq uently positive for estrogen receptor (ER) (70% versus 14%; P = 0.03). The presence of EGFR correlated with positive lymph node status (P = 0.004), poor differentiation (P = 0.001), and negative ER status (P = 0.0001). EGFR staining was more common in neoplasms which recurred, bu t this approached significance only in the group with node-negative di sease (mean follow-up, 52 months; P = 0.06), and neoplastic cell TGF-a lpha correlated with disease recurrence in patients with node-positive disease (no recurrence, -13% positive versus recurrence, -52% positiv e; P = 0.01). Concurrent TGF-alpha/EGFR staining, present in 18% of tu mors, also was predictive of disease recurrence (no recurrence, 3% pos itive for both versus recurrence, 31% positive for both, P = 0.03). Co nclusions. TGF-alpha is heterogeneously expressed in neoplastic and ho st-derived components of breast tumors. Concurrent EGFR/TGF-alpha immu nostaining may characterize a clinically aggressive subset of breast c arcinomas, possibly reflecting autocrine interaction, and conferring g rowth advantage or metastatic phenotype.