CHANGING PATTERN OF EXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA IN THE PROGRESSION OF PROSTATICNEOPLASMS

The autocrine/paracrine interaction of the epidermal growth factor rec eptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evalu ate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesi ons. The specimens evaluated included 37 primary carcinomas (34 hormon e-naive and 3 hormone-refractory tumors) and 22 metastases. For each s pecimen, the pattern of expression was evaluated and staining reactivi ties graded from 0-3, with 0 representing no staining and 3 representi ng homogeneous and intense staining. Primary malignant prostate epithe lial cells in areas with discrete gland formation showed strong EGFr i mmunostaining, while stromal cells were generally nonreactive. In untr eated primary tumors, TGF-alpha expression was primarily in the stroma , while epithelial cells were weakly positive in several cases. Malign ant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-r efractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metasta ses coexpressed the receptor and the ligand. These results suggest tha t, unlike primary prostate tumors where a paracrine relationship betwe en EGFr and TGF-alpha appears to predominate, the potential for autocr ine stimulation may exist in the majority of metastatic androgen-indep endent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androge n-independent condition suggests that strategies aimed at blocking thi s growth factor pathway may be of therapeutic importance for androgen- independent disease.