Interaction of transforming growth factor-alpha and epidermal growth factor receptor in breast carcinoma: An immunohistologic study

R. Castellani, Daniel W Visscher, S. Wykes, F. H. Sarkar, J. D. Crissman

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32 Scopus citations


Background. Interaction of transforming growth factor-alpha (TGF-α) with its receptor, epidermal growth factor receptor (EGFR), has been implicated as an autoregulatory autocrine mechanism of breast epithelial proliferation. Methods. To examine the interrelationship and clinical relevance of TGF-α and EGFR in breast carcinoma, methanol-fixed cryostat sections from 73 patients were immunostained with monoclonal antibodies to epidermal growth factor (EGF), EGFR, and TGF-α. Results. Neither EGFR nor TGF-α staining was diagnostic or specific for the detection of malignant neoplastic cells. Both exhibited staining along the basal lamina of most benign ducts and lobules. TGF-α 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-α failed to correlate with node status or grade; however, TGF-α negative tumors were more frequently 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, but this approached significance only in the group with node-negative disease (mean follow-up, 52 months; P = 0.06), and neoplastic cell TGF-α correlated with disease recurrence in patients with node-positive disease (no recurrence, -13% positive versus recurrence, - 52% positive; P = 0.01). Concurrent TGF-α/EGFR staining, present in 18% of tumors, also was predictive of disease recurrence (no recurrence, 3% positive for both versus recurrence, 31% positive for both, P = 0.03). Conclusions. TGF-α is heterogeneously expressed in neoplastic and host-derived components of breast tumors. Concurrent EGFR/TGF-α immunostaining may characterize a clinically aggressive subset of breast carcinomas, possibly reflecting autocrine interaction, and conferring growth advantage or metastatic phenotype.

Original languageEnglish (US)
Pages (from-to)344-349
Number of pages6
Issue number2
StatePublished - 1994
Externally publishedYes



  • breast carcinoma
  • epidermal growth factor receptor
  • immunoperoxidase
  • transforming growth factor-alpha

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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