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

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. © 2000 Wiley‐Liss, Inc.