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

Richard K. Yang, Pei Zhao, Changxue Lu, Jun Luo, Rong Hu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalHuman Pathology
Volume84
DOIs
StatePublished - Feb 1 2019

Fingerprint

Salivary Ducts
Androgen Receptors
Androgens
Carcinoma
Immunohistochemistry
In Situ Hybridization
Castration
Hepatocyte Nuclear Factor 3-alpha
Therapeutics
Reverse Transcription
Prostatic Neoplasms

Keywords

  • Androgen receptor
  • Androgen-deprivation therapy
  • AR-V7
  • Immunohistochemistry
  • RNA in situ hybridization
  • Salivary duct carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy–naïve salivary duct carcinomas. / Yang, Richard K.; Zhao, Pei; Lu, Changxue; Luo, Jun; Hu, Rong.

In: Human Pathology, Vol. 84, 01.02.2019, p. 173-182.

Research output: Contribution to journalArticle

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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-na{\"i}ve 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.",
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AB - 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.

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