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

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Abstract
Epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor-α (TGF-α), play an important role through the autocrine growth-regulation system in several human cancers, including breast cancer. However, the clinical significance of co-expression of EGF-R and TGF-α has not 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 months (median 94 months) post-operatively. Immunoreactivity for EGF-R, TGF-α, p53 and c-erbB-2 with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Positive rates of carcinoma cells were 27%, 33%, 32% and 26% for EGF-R, TGF-α, p53 and c-erbB-2, respectively. Expression of EGF-R only was observed in 16% (28/173), of TGF-α only in 22% (38/173), of both EGF-R and TGF-α 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 co-expression of EGF-R and TGF-α (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 size (p = 0.0001, p < 0.0001) and c-erbB-2 expression (p = 0.0034, p = 0.018), respectively. The status of p53 expression (p = 0.01), estrogen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed significant differences in overall survival. According to Cox's multivariate analysis, co-expression of EGF-R and TGF-α had the most significant effect on disease-free survival (p < 0.0001) and overall survival (p < 0.0001), followed by nodal status. Co-expression of EGF-R and TGF-α by immunohistochemical detection is an independent prognostic indicator, and it may be helpful for determining the group of breast-cancer patients with an aggressive phenotype. Int. J. Cancer 89:484–487, 2000.