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

被引：17
作者：
Yang, Richard K. [1 ]
Zhao, Pei [2 ]
Lu, Changxue [2 ]
Luo, Jun [2 ]
Hu, Rong [1 ]
机构：
[1] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA
[2] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD 21287 USA
来源：
HUMAN PATHOLOGY | 2019年 / 84卷
关键词：
Salivary duct carcinoma; Androgen-deprivation therapy; Androgen receptor; AR-V7; RNA in situ hybridization; Immunohistochemistry; VARIANTS; TRASTUZUMAB; ABIRATERONE;
D O I：
10.1016/j.humpath.2018.09.009
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
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-naive 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. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码：173 / 182
页数：10
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