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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.

SUBMITTER: Xu B

PROVIDER: S-EPMC6937722 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Xu Bin B Dogan Snjezana S Haroon Al Rasheed Mohamed Rizwan MR Ghossein Ronald R Katabi Nora N

Human pathology 20190817

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 SD ...[more]

PMID: 31430492

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Project description:IMPORTANCE:Salivary duct carcinoma is a rare, aggressive malignancy of the salivary glands. Owing to its rare nature, clinical data are limited, and only a few clinical studies comprise more than 50 patients. OBJECTIVE:To review the University of Pittsburgh Medical Center's experience with salivary duct carcinoma over a 20-year period, focusing on demographics, presentation, treatment, and outcome. DESIGN, SETTING, AND PARTICIPANTS:This investigation was a retrospective cohort study in a multihospital institution with tertiary referral. A pathology database was reviewed for all cases of histopathologically diagnosed salivary duct carcinoma from January 1, 1995, to October 20, 2014. Patients who were referrals for pathology review only and were never seen at the institution were excluded. In total, 75 study patients were identified. The electronic medical record was reviewed for details regarding demographics, presentation, treatment, and outcome, including overall survival (OS) and disease-free survival (DFS). This study was supplemented with a review of the institution's Head and Neck Oncology Database for further clinical details. MAIN OUTCOMES AND MEASURES:Primary outcome measures consisted of OS and DFS. RESULTS:The study sample comprised 75 participants with a mean age at diagnosis of 66.0 years (age range, 33-93 years), and 29% (n?=?22) were female. Most primary tumors were from the parotid gland (83%), with the next most frequent site being the submandibular gland (12%). Overall, 41% of the cases were carcinoma ex pleomorphic adenoma. Rates of other histologic features included the following: perineural invasion (69%), extracapsular spread (58%), ERBB2 (formerly HER2) positivity (31%) (62% of those who were tested), and vascular invasion (61%). The median OS was 3.1 years, and the median DFS was 2.7 years. Univariate Kaplan-Meier survival analyses demonstrated that facial nerve sacrifice and extracapsular spread were associated with lower OS (2.38 vs 5.11 years and 2.29 vs 6.56 years, respectively) and DFS (2.4 vs 3.88 years and 1.44 vs 4.5 years, respectively). Although underpowered, multivariable analysis demonstrated significantly worse OS in patients with N2 and N3 disease (hazard ratio [HR] 8.42, 95% CI, 1.84-38.5) but did not show significantly worse DFS or OS for facial nerve sacrifice or extracapsular spread. There was no association between ERBB2 positivity and survival and no difference in survival between patients receiving radiation therapy vs radiation therapy plus chemotherapy. No patients had recurrence or distant metastasis after 5 disease-free years. CONCLUSIONS AND RELEVANCE:Salivary duct carcinoma is an aggressive disease. A large number of cases in this review were carcinoma ex pleomorphic adenoma and had classic negative prognostic indicators, such as perineural invasion, vascular invasion, and extracapsular spread. ERBB2 positivity was not associated with any difference in survival. Facial nerve involvement appears to indicate worse prognosis, as does nodal stage higher than N1. Recurrence and metastasis after 5 years are rare.

Project description:BackgroundThe efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown.MethodsOverall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC.ResultsPatients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB.ConclusionPatients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

Dataset Information

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

Publications

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

Similar Datasets

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