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 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.


METHODS
Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs.


METHODS
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.


CONCLUSIONS
An AR-mediated TGF-alpha/EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.
Fan
C Y
CY
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA.
Melhem
M F
MF
Hosal
A S
AS
Grandis
J R
JR
Barnes
E L
EL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000096:biosynthesis*; D012189:Retrospective Studies; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*
D011944:Receptors, Androgen; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors