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癌-睾丸抗原PRAME的免疫组织化学检测

Immunohistochemical Detection of Cancer-Testis Antigen PRAME.

作者信息

Lezcano Cecilia, Müller Annette M, Frosina Denise, Hernandez Enmily, Geronimo Jerica A, Busam Klaus J, Jungbluth Achim A

机构信息

5803Memorial Sloan-Kettering Cancer Center, New York, USA.

27182University Hospital of Cologne, Cologne, Germany.

出版信息

Int J Surg Pathol. 2021 Dec;29(8):826-835. doi: 10.1177/10668969211012085. Epub 2021 Apr 23.

Abstract

Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.

摘要

癌-睾丸(CT)抗原是根据其在自体宿主中引发T细胞或B细胞免疫反应的能力而确定的。它们通常在多种肿瘤中表达,而在正常成人组织中则仅限于睾丸生殖细胞。黑色素瘤优先表达抗原(PRAME)是非经典CT抗原家族的成员,除睾丸外还在其他一些正常组织中表达。有趣的是,由于用于免疫组织化学检测的试剂有限,许多CT抗原的蛋白质表达情况仍不完整。在此,我们测试了几种市售血清学试剂,并鉴定出一种适用于在福尔马林固定石蜡包埋标本中免疫组织化学检测PRAME的单克隆抗体。我们还测试了多种正常组织和肿瘤组织。PRAME在正常组织中的蛋白表达与睾丸中原始分子数据一致,在子宫内膜、肾上腺皮质、成年及胎儿卵巢中表达水平较低。在肿瘤中,大多数转移性黑色素瘤、黏液样脂肪肉瘤和滑膜肉瘤中存在弥漫性PRAME免疫反应性。其他肿瘤,如精原细胞瘤和各种起源的癌,包括子宫内膜癌、浆液性卵巢癌、乳腺导管癌、肺癌和肾癌,PRAME蛋白表达呈阳性的病例比例中等,肿瘤细胞阳性程度各异。与其他CT抗原一样,肝细胞癌、结直肠癌、睾丸间质细胞瘤、间皮瘤和平滑肌肉瘤是PRAME的低表达者。

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