Expression of Androgen Receptor and Prostatic Specific Markers in Salivary Duct Carcinoma

Abstract

Salivary duct carcinoma (SDC) is an uncommon, pathologically distinct entity characterized by its morphologic resemblance to ductal carcinoma of the breast and highly aggressive behavior. Approximately two thirds of patients die within 4 years of initial diagnosis despite aggressive, combined surgical resection and radiotherapy. Review of the literature indicates that androgen receptor (AR), a marker frequently detected in prostatic carcinoma, is expressed in over 90% of SDCs, whereas two common breast carcinoma markers, estrogen and progesterone receptors (ER and PR), are expressed in only 1.3% and 6% of the tumors, respectively, by immunohistochemistry. This hormonal profile suggests that SDC, in contrast to its histiologic similarity to ductal carcinoma of the breast, is immunophenotypically more related to prostatic carcinoma. To substantiate this hypothesis, we performed immunohistochemical staining of 13 cases of SDC for the presence of AR and two prostatic markers, prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Our results showed multifocal, scattered, moderate immunostaining for PAP and diffuse, moderate immunostaining for PSA in seven (58.3%) and two (16.7%) cases, respectively. These results create a potential diagnostic challenge to surgical pathologists who are dealing with a metastatic adenocarcinoma of AR+/PSA+/-/PAP+/- phenotype, particularly in male patients of unknown primary. Metastatic salivary duct carcinoma should be given serious thought if clinical investigation fails to reveal a prostatic primary. The immunophenotypic homology that exists between SDC and prostatic carcinoma also suggests that antiandrogen therapy as used in the treatment of prostatic carcinoma might be beneficial in patients with metastatic SDC when all other conventional modalities fail.

Salivary Gland Neoplasia: A Review for the Practicing Pathologist

“…Oddly, 58% of SDC also stain for prostatic acid phosphatase and 17% for prostate specific antigen. In addition, roughly 90% of SDC bear androgen receptors by immunohistochemistry, which may prove to be a fruitful target for therapeutic hormonal intervention (98).…”

Carcinoma Ex Pleomorphic Adenoma: Case Report and Options for Systemic Therapy

“…High expression of androgen receptor has led to case reports describing responses to androgen deprivation therapy 5 . A potentially receptorindependent response to tamoxifen has also been demonstrated; however, more prospective data are needed to establish a role for hormonal therapy 6 .…”

An immunohistochemical study of androgen receptor in carcinoma arising in pleomorphic salivary adenoma

“…AR mediates the effect of androgen by binding to specific DNA sequences and influences the transcription and translation of various genes (20,21). Fan et al, (22,23) suggested that AR may have a role in the pathogenesis of salivary duct carcinoma through the mediation of an epidermal growth factor receptor and transforming growth factor-α autocrine pathway similar to that seen in prostatic carcinoma. Nasser et al, (24) showed negative reactivity to androgen receptor in benign gland tumors, but positive reactivity was detected in two of ten mucoepidermoid carcinomas, two of ten adenoid cystic carcinomas, and most cases of salivary duct carcinoma.…”