Expression Of Androgen Receptor, Epidermal Growth Factor Receptor, And Transforming Growth Factor Alpha In Salivary Duct Carcinoma

Abstract

Background: Salivary duct carcinoma (SDC) is a rare, highly aggressive neoplasm that primarily affects the major salivary glands. It is a distinct clinicopathological entity characterized by its morphologic resemblance to ductal carcinoma of the breast, a high incidence of regional lymph node metastasis, and distant dissemination. Frequent expression of androgen receptor (AR) but not estrogen receptor or progesterone receptor in SDCs suggests that SDC bears a close immunophenotypic homology with prostatic carcinoma. An AR-mediated autocrine growth pathway consisting of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), has been implicated in the carcinogenesis of prostatic carcinoma. Androgens, in the presence of AR, mediate their mitogenic effects on prostatic cancer cells by up-regulating the transcriptional and translational activities of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha produced in the tumor cells binds to its receptor, EGFR, which is also ex-pressed by these cells, resulting in a proliferative response. Objective: To investigate whether a TGF-alpha /EGFR autocrine pathway is present in SDCs. Design: Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs. Setting: An academic medical center. Results: Salivary duct carcinoma expresses AR, TGF-alpha, and EGFR in 11 (92%), 8 (67%), and 11 (92%) of 12 cases, respectively. Conclusion: An AR-mediated TGF-alpha /EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.