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Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy-naive salivary duct carcinomas.

ABSTRACT: Androgen-deprivation therapy has been used to treat salivary duct carcinoma (SDC). The androgen receptor splice variant-7 (AR-V7) has been detected in castration-resistant prostate cancer and implicated in resistance to androgen receptor (AR)-targeted therapies. Given the potential role of AR/AR-V7 in SDC treatment, this study focuses on AR/AR-V7 expression in SDC specimens collected before androgen-deprivation therapy. RNA in situ hybridization (ISH) and immunohistochemistry (IHC) to detect total AR and AR-V7 were performed on formalin-fixed, paraffin-embedded SDC specimens from 23 patients. Full-length AR and AR-V7 transcripts were quantified in a subset of tumors by reverse-transcription polymerase chain reaction. Twenty SDCs were positive for total AR by ISH and IHC. Among AR-positive SDCs, 70% (14/20) were positive for AR-V7 messenger RNA by ISH, whereas 15% (3/20) were positive for AR-V7 protein by IHC. The 3 SDCs that expressed the highest levels of AR-V7 were all from female patients; one of them expressed a significant amount of AR-V7 and barely detectable full-length AR transcripts by reverse-transcription polymerase chain reaction. IHC expression of Forkhead box protein A1, prostate-specific antigen, prostatic acid phosphatase, and NKX3.1 was observed in some SDCs regardless of patient sex. Five SDCs demonstrated strong human epidermal growth factor receptor 2 expression. We conclude that treatment-naïve SDCs may express AR-V7 at levels comparable to or even exceeding the levels detected in castration-resistant prostate cancer. Our data support the feasibility to incorporate AR-V7 assessment via ISH and/or IHC in the ongoing clinical trials evaluating the therapeutic benefit of AR-targeted therapies in SDC patients.

SUBMITTER: Yang RK

PROVIDER: S-EPMC7098468 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy-naïve salivary duct carcinomas.

Yang Richard K RK Zhao Pei P Lu Changxue C Luo Jun J Hu Rong R

Human pathology 20180926

Androgen-deprivation therapy has been used to treat salivary duct carcinoma (SDC). The androgen receptor splice variant-7 (AR-V7) has been detected in castration-resistant prostate cancer and implicated in resistance to androgen receptor (AR)-targeted therapies. Given the potential role of AR/AR-V7 in SDC treatment, this study focuses on AR/AR-V7 expression in SDC specimens collected before androgen-deprivation therapy. RNA in situ hybridization (ISH) and immunohistochemistry (IHC) to detect tot ...[more]

PMID: 30267779

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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

Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy-naive salivary duct carcinomas.

Publications

Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy-naïve salivary duct carcinomas.

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