Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma

Background: Salivary duct carcinoma (SDC) is a rare, highly aggressive neop lasm that primarily affects the major salivary glands. It is a distinct cli nicopathological entity characterized by its morphologic resemblance to duc tal carcinoma of the breast, a high incidence of regional lymph node metast asis, and distant dissemination. Frequent expression of androgen receptor ( AR) but not estrogen receptor or progesterone receptor in SDCs suggests tha t 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. Androg ens, in the presence of AR, mediate their mitogenic effects on prostatic ca ncer cells by up-regulating the transcriptional and translational activitie s of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha pro duced in the tumor cells binds to its receptor, EGFR, which is also ex-pres sed by these cells, resulting in a proliferative response. Objective: To investigate whether a TGF-alpha /EGFR autocrine pathway is pr esent 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 (9 2%), 8 (67%), and 11 (92%) of 12 cases, respectively. Conclusion: An AR-mediated TGF-alpha /EGFR autocrine pathway may be implica ted in the tumorigenesis of SDC.