Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
Department of Clinical and Experimental Pathology, Wroclaw Medical University, Wrocław.
Am J Surg Pathol. 2022 Nov 1;46(11):1467-1476. doi: 10.1097/PAS.0000000000001944. Epub 2022 Aug 16.
Preferentially expressed antigen in melanoma (PRAME) is considered a useful marker in the differential diagnosis between malignant melanoma and its melanocytic mimics. Recently PRAME expression was documented in nonmelanocytic tumors, but much of the data are based on mRNA studies. This investigation evaluated PRAME expression in the spectrum of normal tissues and >5800 human tumors using immunohistochemistry and EP461 monoclonal antibody. In normal tissues, PRAME was expressed in the testis and proliferative endometrium. In tumors, PRAME was variably expressed in malignancies of different lineages. Among epithelial tumors, >50% of PRAME-positive lesions were found among endometrial carcinomas (82%), uterine serous carcinomas (82%), uterine carcinosarcomas (60%), ovarian clear cell carcinomas (90%), ovarian serous carcinomas (63%), adenoid cystic carcinomas (81%), seminomas (78%), thymic carcinomas (75%), and basal cell carcinomas (62%). In mesenchymal and neuroectodermal malignancies, PRAME was frequently expressed in synovial sarcoma (71%), myxoid liposarcoma (76%), neuroblastoma (61%) and metastatic melanoma (87%). Also, PRAME was consistently expressed in 4 melanomas that lacked all melanoma markers including S100 protein and SOX10 but harbored typical for melanoma BRAF or NRAS driver mutations. However, strong and diffuse PRAME immunoreactivity was seen in many types of nonmelanocytic poorly differentiated carcinomas and sarcomas. Based on this study, PRAME is a relatively unspecific immunohistochemical marker, which limits its use in diagnostic surgical pathology. However, immunohistochemistry is a reliable and unexpensive method useful in detecting PRAME-positive malignancies for potential immunotherapy.
黑色素瘤中优先表达的抗原（PRAME）被认为是鉴别恶性黑色素瘤与其黑色素细胞类似物的有用标志物。最近，PRAME 表达已在非黑色素细胞肿瘤中得到证实，但大部分数据基于 mRNA 研究。本研究使用免疫组织化学和 EP461 单克隆抗体评估了 PRAME 在正常组织和 >5800 个人类肿瘤中的表达。在正常组织中，PRAME 在睾丸和增殖性子宫内膜中表达。在肿瘤中，PRAME 在不同谱系的恶性肿瘤中呈不同程度的表达。在上皮性肿瘤中，>50%的 PRAME 阳性病变见于子宫内膜癌（82%）、子宫浆液性癌（82%）、子宫癌肉瘤（60%）、卵巢透明细胞癌（90%）、卵巢浆液性癌（63%）、腺样囊性癌（81%）、精原细胞瘤（78%）、胸腺癌（75%）和基底细胞癌（62%）。在间充质和神经外胚层恶性肿瘤中，PRAME 在滑膜肉瘤（71%）、黏液样脂肪肉瘤（76%）、神经母细胞瘤（61%）和转移性黑色素瘤（87%）中常表达。此外，在 4 例缺乏所有黑色素瘤标志物（包括 S100 蛋白和 SOX10）但携带典型黑色素瘤 BRAF 或 NRAS 驱动突变的黑色素瘤中，PRAME 也持续表达。然而，许多类型的非黑色素细胞低分化癌和肉瘤中也可见到强烈和弥漫的 PRAME 免疫反应性。基于本研究，PRAME 是一种相对非特异性的免疫组化标志物，限制了其在诊断外科病理学中的应用。然而，免疫组织化学是一种可靠且廉价的方法，可用于检测潜在免疫治疗的 PRAME 阳性恶性肿瘤。
