Cy. Fan et al., Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma, ARCH OTOLAR, 127(9), 2001, pp. 1075-1079
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.