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Expression of Androgen Receptor, Epidermal Growth Factor Receptor, and Transforming Growth Factor  in Salivary Duct Carcinoma
Chun-Yang Fan, MD, PhD;
Mona F. Melhem, MD;
A. Sefik Hosal, MD;
J. Rubin Grandis, MD;
E. Leon Barnes, MD
Arch Otolaryngol Head Neck Surg. 2001;127:1075-1079.
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  (TGF-), 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-.
Through an autocrine mode of action, TGF- 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-/EGFR autocrine pathway is present
in SDCs.
Design Retrospective analysis of the expression of AR, EGFR, and TGF-
in 12 SDCs.
Setting An academic medical center.
Results Salivary duct carcinoma expresses AR, TGF-, and EGFR in 11 (92%),
8 (67%), and 11 (92%) of 12 cases, respectively.
Conclusion An AR-mediated TGF-/EGFR autocrine pathway may be implicated
in the tumorigenesis of SDC.
From the Department of Pathology, University of Arkansas for Medical
Sciences, Little Rock (Dr Fan); Department of Pathology, Veterans Affairs
Medical Center, Pittsburgh, Pa (Dr Melhem); Department of Otolaryngology,
Hacettepe University Medical Faculty, Ankara, Turkey (Dr Hosal); and Departments
of Otolaryngology (Dr Grandis) and Pathology (Dr Barnes), University of Pittsburgh
School of Medicine, Pittsburgh, Pa.
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