Can Nhu Thuy, Lingen Mark W, Mashek Heather, McElherne James, Briese Renee, Fitzpatrick Carrie, van Zante Annemieke, Cipriani Nicole A
Department of Pathology, The University of Chicago Medicine, 5841 S. Maryland Ave, MC 6101, Chicago, IL, 60637, USA.
Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
Head Neck Pathol. 2018 Mar;12(1):95-104. doi: 10.1007/s12105-017-0833-y. Epub 2017 Jul 5.
With the advent of targeted therapies, expression of sex hormone receptors and HER-2 in salivary gland tumors (SGTs) is of clinical interest. Previous reports of estrogen (ER) and progesterone (PR) receptor expression have varied. Androgen receptor (AR) and HER-2 overexpression are frequently reported in salivary duct carcinoma (SDC), but have not been studied systematically in other SGTs. This study examines ER, PR, AR, and HER-2 expression in SGTs. Immunohistochemistry for ER, PR, AR, and HER-2 was performed on 254 SGTs (134 malignant). ER, PR, and AR expression was scored using Allred system. HER-2 expression was scored using Dako HercepTest guidelines. FISH for HER-2 amplification was performed on select cases with HER-2 overexpression (2-3+). No SGT demonstrated strong expression of ER or PR. Combined strong AR and HER-2 expression was seen in 22 carcinomas: 14/25 SDC, 3/16 poorly differentiated, two oncocytic, and one each carcinoma ex pleomorphic adenoma, squamous cell, and intraductal carcinoma. Eighteen additional high grade carcinomas had HER-2 overexpression with absent, weak, or moderate AR expression; eight high grade carcinomas had isolated strong AR expression with 0-1+ HER-2 staining. Of 15 tested cases, six demonstrated HER-2 amplification by FISH, all of which had 3+ immunoreactivity. Neither benign nor malignant SGTs had strong expression of ER or PR. None of the benign SGTs overexpressed AR or HER-2. Coexpression of AR and HER-2 should not define SDC, but immunostaining should be considered in high grade salivary carcinomas, as some show overexpression and may benefit from targeted therapy.
随着靶向治疗的出现,唾液腺肿瘤(SGTs)中性激素受体和HER-2的表达具有临床意义。先前关于雌激素(ER)和孕激素(PR)受体表达的报道各不相同。雄激素受体(AR)和HER-2过表达在涎腺导管癌(SDC)中经常被报道,但在其他SGTs中尚未进行系统研究。本研究检测了SGTs中ER、PR、AR和HER-2的表达。对254例SGTs(134例恶性)进行了ER、PR、AR和HER-2的免疫组织化学检测。ER、PR和AR表达采用Allred系统评分。HER-2表达采用Dako HercepTest指南评分。对部分HER-2过表达(2-3+)的病例进行HER-2扩增的荧光原位杂交(FISH)检测。没有SGT显示出ER或PR的强表达。22例癌中可见AR和HER-2联合强表达:25例SDC中的14例、16例低分化癌中的3例、2例嗜酸细胞癌、1例癌肉瘤、1例鳞状细胞癌和1例导管内癌。另外18例高级别癌有HER-2过表达且AR表达缺失、弱或中等;8例高级别癌有孤立的AR强表达且HER-2染色为0-1+。在15例检测病例中,6例通过FISH显示HER-2扩增,所有这些病例均有3+免疫反应性。良性和恶性SGTs均无ER或PR的强表达。良性SGTs均未过表达AR或HER-2。AR和HER-2的共表达不应定义为SDC,但在高级别涎腺癌中应考虑免疫染色,因为一些病例显示过表达且可能从靶向治疗中获益。