Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients

Epidermal growth factor receptor (EGF-R) and its ligand, transforming growt h factor-a (TGF-alpha), play an important role through the autocrine growth -regulation system in several human cancers, including breast cancer. Howev er, the clinical significance of co-expression of EGF-R and TGF-alpha has n ot been elucidated. One hundred seventy-three female patients diagnosed as invasive ductal carcinoma who had undergone a mastectomy (159 patients) or breast-conserving surgery(14 patients) were followed up for 81 to 119 month s (median 94 months) post-operatively, Immunoreactivity for EGF-R, TGF-alph a, p53 and c-erbB-2 with paraffin-embedded carcinoma tissue was investigate d using labeled streptavidinbiotin methods. Positive rates of carcinoma cel ls were 27%, 33%, 32% and 26% for EGF-R, TGF-alpha, p53 and c-erbB-2, respe ctively. Expression of EGF-R only was observed in 16% (28/173), of TGF-alph a only in 22% (38/173), of both EGF-R and TGF-alpha in 11% (19/173) and of neither in 51% (88/173). By univariate analysis, significant differences in overall survival and disease-free survival were noted according to the coe xpression of EGF-R and TGF-alpha (p < 0.0001, p < 0.0001), co-expression of EGF-R and c-erbB-2 (p = 0.0029, p 0.0028), nodal status (p = 0.0028, p = 0 .0001), tumor sire (p = 0.0001,p < 0.0001) and c-erbB-2 expression (p = 0.0 034, p = 0.018), respectively. The status of p53 expression (p 0.01), estro gen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed signi ficant differences in overall survival. According to Cox's multivariate ana lysis, co-expression of EGF-R and TGF-alpha had the most significant effect on disease-free survival (p < 0.0001) and overall survival (p < 0.0001), f ollowed by nodal status. Go-expression of EGF-R and TGF-alpha by immunohist ochemical detection is an independent prognostic indicator, and it may be h elpful for determining the group of breast-cancer patients with an aggressi ve phenotype. Int. J. Cancer(Pred. Oncol.) 89:484-487, 2000. (C) 2000 Wiley -Liss, Inc.