title: Interaction of transforming growth factor-alpha and epidermal growth factor receptor in breast carcinoma. An immunohistologic study.
abstract: 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 epithelial proliferation.
  
  
  METHODS
  To examine the interrelationship and clinical relevance of TGF-alpha 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-alpha.
  
  
  RESULTS
  Neither EGFR nor TGF-alpha 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-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 node status or grade; however, TGF-alpha 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-alpha correlated with disease recurrence in patients with node-positive disease (no recurrence, -13% positive versus recurrence, -52% positive; P = 0.01). Concurrent TGF-alpha/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-alpha is heterogeneously expressed in neoplastic and host-derived components of breast tumors. Concurrent EGFR/TGF-alpha immunostaining may characterize a clinically aggressive subset of breast carcinomas, possibly reflecting autocrine interaction, and conferring growth advantage or metastatic phenotype.
authors.affiliation: Department of Pathology, Harper Hospital, Detroit, Michigan 48201.
authors.forename: R
authors.initials: R
authors.lastname: Castellani
authors.forename: D W
authors.initials: DW
authors.lastname: Visscher
authors.forename: S
authors.initials: S
authors.lastname: Wykes
authors.forename: F H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: J D
authors.initials: JD
authors.lastname: Crissman
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local; D011960:Receptors, Estrogen / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000502:physiology*
chemical_list: D011960:Receptors, Estrogen; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors