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

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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
JournalCancer
Volume73
Issue number2
DOIs
StatePublished - Jan 15 1994

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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