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  • Title: Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma.
    Author: Fan CY, Melhem MF, Hosal AS, Grandis JR, Barnes EL.
    Journal: Arch Otolaryngol Head Neck Surg; 2001 Sep; 127(9):1075-9. PubMed ID: 11556855.
    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 expressed 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.
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