Androgen receptor immunohistochemistry in salivary duct carcinoma: a retrospective study of 188 cases focusing on tumoral heterogeneity and temporal concordance

Abstract

Salivary duct carcinoma (SDC) is a high-grade salivary gland carcinoma that is associated with frequent metastasis and poor outcome. Androgen receptor (AR) immunoexpression in SDC is reported in 69% to 100% of SDC. Androgen deprivation therapy (ADT) has shown a response rate of 18% to 42% in SDC. Therefore, AR immunoexpression may serve as a diagnostic and predictive marker for ADT response in SDC. We investigated AR immunopositivity and staining pattern in a large retrospective cohort of 188 SDCs from 163 patients, including 22 paired primary and metastatic SDCs from the same patients, focusing specifically on staining heterogeneity and concordance. A control cohort of 61 non-SDC salivary gland carcinomas was also included. AR immunopositivity defined as ≥1% of tumor cell nuclear staining was found in 94% (177/188) of SDCs, including 95% of primary tumors, 100% of regional metastases, and 90% of distant metastases. Most of the cases (75%, 86/114) showed homogeneous and diffuse AR positivity. However, a subset (25%) exhibited focal or heterogeneous AR staining pattern. Although most metastases (21/22, 95%) had concordant AR expression with the primary tumors, one treatment-naïve tumor (5%) had complete loss of AR immunoexpression in the metastasis without detectable molecular alterations in AR or AR co-regulators. AR positive staining in non-SDC salivary carcinomas was infrequent (15%, 9/61), and mostly heterogeneous or focal. AR immunoexpression is highly prevalent in SDC, in both primary (94%) and metastatic tumors (93%). The cumulative AR immunopositivity rate in SDC is 90% based on data from the current study and previous literature. A small subset may show intratumoral AR heterogeneity and discordant AR expression in metastasis. AR immunoexpression may be seen in non-SDC salivary gland carcinomas but it is uncommon and usually focal.