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滑膜肉瘤中癌-睾丸抗原的表达:NY-ESO-1、PRAME、MAGEA4和MAGEA1

Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1.

作者信息

Iura Kunio, Maekawa Akira, Kohashi Kenichi, Ishii Takeaki, Bekki Hirofumi, Otsuka Hiroshi, Yamada Yuichi, Yamamoto Hidetaka, Harimaya Katsumi, Iwamoto Yukihide, Oda Yoshinao

机构信息

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

出版信息

Hum Pathol. 2017 Mar;61:130-139. doi: 10.1016/j.humpath.2016.12.006. Epub 2016 Dec 16.

Abstract

Synovial sarcoma (SS) is regarded as a relatively chemosensitive sarcoma, but the prognosis of advanced SSs remains poor. Here we identified highly expressed cancer-testis antigens that could be promising immunotherapy targets for SS, using a previously conducted cDNA microarray, and we assessed the clinicopathological or prognostic relationships of these antigens in SS. We compared the gene expression profiles of 11 SSs with those of 3 normal adipose tissues. Among the up-regulated cancer-testis antigens, we analyzed PRAME, MAGEA1, and MAGEA4 and another cancer-testis antigen (NY-ESO-1) together, by immunohistochemistry and real-time polymerase chain reaction in 108 SSs. Immunohistochemically, NY-ESO-1, PRAME, MAGEA4, and MAGEA1 were positive in 66 (61%), 93 (86%), 89 (82%), and 16 (15%) of 108 SSs, respectively, and 104 (96%) of 108 SSs showed the immunohistochemical expression of at least 1 of NY-ESO-1, PRAME, and MAGEA4. Moreover, the high expression of at least 1 of these 3 antigens was observed in 83% of the SSs. High expression of NY-ESO-1 and MAGEA4 was significantly correlated with the presence of necrosis and advanced clinical stage. The immunohistochemical expression of these cancer-testis antigens was not correlated with prognosis, but the coexpression of NY-ESO-1, PRAME, and MAGEA4 was significantly associated with adverse prognosis. The real-time polymerase chain reaction results were closely related to the immunohistochemical results: NY-ESO-1 (P = .0019), PRAME (P = .039), MAGEA4 (P = .0149), and MAGEA1 (P = .0766). These data support the potential utility of NY-ESO-1, PRAME, and MAGEA4 as immunotherapy targets and ancillary prognostic parameters, suggesting the possible benefit of the combined use of these cancer-testis antigens as an SS immunotherapy target.

摘要

滑膜肉瘤(SS)被认为是一种相对对化疗敏感的肉瘤,但晚期SS的预后仍然很差。在此,我们利用先前进行的cDNA微阵列鉴定出了高表达的癌睾丸抗原,这些抗原可能是SS有前景的免疫治疗靶点,并且我们评估了这些抗原在SS中的临床病理或预后关系。我们将11例SS的基因表达谱与3例正常脂肪组织的基因表达谱进行了比较。在上调的癌睾丸抗原中,我们通过免疫组织化学和实时聚合酶链反应,对108例SS中的PRAME、MAGEA1、MAGEA4以及另一种癌睾丸抗原(NY-ESO-1)进行了联合分析。免疫组织化学结果显示,在108例SS中,NY-ESO-1、PRAME、MAGEA4和MAGEA1阳性率分别为66例(61%)、93例(86%)、89例(82%)和16例(15%),108例SS中有104例(96%)显示NY-ESO-1、PRAME和MAGEA4中至少有一种的免疫组织化学表达。此外,在83%的SS中观察到这3种抗原中至少有一种高表达。NY-ESO-1和MAGEA4的高表达与坏死的存在和晚期临床分期显著相关。这些癌睾丸抗原的免疫组织化学表达与预后无关,但NY-ESO-1、PRAME和MAGEA4的共表达与不良预后显著相关。实时聚合酶链反应结果与免疫组织化学结果密切相关:NY-ESO-1(P = .0019)、PRAME(P = .039)、MAGEA4(P = .0149)和MAGEA1(P = .0766)。这些数据支持NY-ESO-1、PRAME和MAGEA4作为免疫治疗靶点和辅助预后参数的潜在效用,表明联合使用这些癌睾丸抗原作为SS免疫治疗靶点可能有益。

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