Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.
Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.
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DOI：
10.1002/cjp2.16
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Oda Y
中科院分区：
文献类型：
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作者：
Iura K;Kohashi K;Hotokebuchi Y;Ishii T;Maekawa A;Yamada Y;Yamamoto H;Iwamoto Y;Oda Y
粘液样脂肪肉瘤是第二常见的脂肪肉瘤。虽然粘液样脂肪肉瘤对化疗相对敏感，因此是一个很好的化疗候选者，但复发或转移性疾病的病例仍然预后不良。在这里，我们进行了基因微阵列分析，比较基因表达谱在6个临床粘液样脂肪肉瘤样本和3个正常脂肪组织样本，并确定分子生物标志物，将是有用的诊断标志物或治疗目标粘液样脂肪肉瘤。这表明癌睾丸抗原PRAME在粘液样脂肪肉瘤中上调。然后，我们进行了免疫组织化学、蛋白质印迹和真实的-时间聚合酶链反应分析，以定量PRAME和另一种癌-睾丸抗原NY-ESO-1在粘液样脂肪肉瘤（n = 93）、去分化（n = 46）、高分化（n = 32）和多形性脂肪肉瘤（n = 14）的临床样本中的表达。免疫组化，PRAME和NY-ESO-1阳性分别见于粘液样脂肪肉瘤的84/93（90%）和83/93（89%），以及去分化的20/46（43%）和3/46（7%），分别为3/32（9%）和1/32（3%）的高分化和7/14（50%）和3/21（21%）的多形性脂肪肉瘤。PRAME和/或NY‐ESO‐1的高免疫组化表达与肿瘤直径、肿瘤坏死的存在、> 5%的圆形细胞成分、较高的组织学分级和晚期临床分期显著相关。在单变量分析中，PRAME和NY-ESO-1高表达与预后不良显著相关。粘液样脂肪肉瘤显示PRAME和NY-ESO-1（CTAG 1B）的蛋白和mRNA表达水平显著高于其他脂肪肉瘤。总之，PRAME和NY-ESO-1（CTAG 1B）在绝大多数粘液样脂肪肉瘤中表达，其高水平表达与肿瘤分级和预后不良相关。我们的研究结果支持PRAME和NY‐ESO‐1作为鉴别诊断的辅助参数和预后生物标志物的潜在用途，并表明在粘液样脂肪肉瘤中开发针对这些癌症睾丸抗原的免疫疗法是必要的。
Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer‐testis antigen PRAME was up‐regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real‐time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer‐testis antigen, NY‐ESO‐1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well‐differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY‐ESO‐1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well‐differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY‐ESO‐1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round‐cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY‐ESO‐1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY‐ESO‐1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY‐ESO‐1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high‐level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY‐ESO‐1 as ancillary parameters for differential diagnosis and as prognostic biomarkers, and indicate that the development of immunotherapy against these cancer‐testis antigens in myxoid liposarcoma would be warranted.