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.
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.
Authors: Michelle D Williams; Dianna B Roberts; Merrill S Kies; Li Mao; Randal S Weber; Adel K El-Naggar Journal: Clin Cancer Res Date: 2010-04-06 Impact factor: 12.531
Authors: Nikolaos G Nikitakis; Mark A Scheper; Vasileios S Papanikolaou; Alexandra Sklavounou; John J Sauk Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Endod Date: 2009-03-09