NY-ESO-1和LAGE-1癌症-睾丸抗原在肝细胞癌的表达

Expression of NY-ESO-1 and LAGE-1 cancer -testis antigens in hepatocellular carcinoma

目的 检测NY- ESO -1和LAGE- 1癌症睾丸抗原在肝细胞癌中的表达,探讨其作为肝细胞癌免疫治疗靶标的可行性及其与肝癌生物学行为的关系。方法 逆转录聚合酶链反应(RT -PCR)和免疫组织化学EnVision二步法检测30例肝细胞癌新鲜标本NY ESO -1和LAGE -1的表达;另将191例肝癌石蜡组织制成芯片观察NY- ESO- 1蛋白在肝癌中的分布和表达。结果NY- ESO -1和LAGE -1基因mRNA在肝癌中的阳性表达率分别是33. 3% (10 /30)和16. 7% (5 /30),至少表达1种基因mRNA者为36 7% (11 /30);NY- ESO -1蛋白主要分布在肝癌细胞胞质,有效标本中NY ESO 1表达13 8% (24 /174),小肝癌、中晚期肝癌、发生转移肝癌中的阳性表达率逐渐升高,分别为6 8% (3 /44)、16 2% (21 /130)、23 1% (12 /52),不发生转移的肝癌仅为9 8% ( 12 /122 ),其中转移组与无转移组之间比较差异有统计学意义(P<0 .05),全部病例癌组织与癌旁组织比较差异有统计学意义(P<0 .01)。NY- ESO-1蛋白的阳性表达与肿瘤大小无关,所有癌旁肝组织均未见NY -ESO -1和LAGE -1的mRNA和蛋白的表达。结论 NY -ESO- 1 /LAGE- 1在肝细胞癌组织中的特异性表达提示其可作为肝细胞癌特异性免疫治疗潜在的靶标;NY -ESO -1在肝癌早期出现,随病情进展表达率逐步增高,转移患者最高。

Objective To study the role of NY-ESO-1 and LAGE-1 cancer-testis antigens a s targets for immunotherapy and the relationship between corresponding gene expr ession and biologic behavior of hepatocellular carcinoma (HCC). Methods The expression of NY-ESO-1 and LAGE-1 was studied in frozen tumor tissues from 30 cases of HCC by reverse transcriptase-polymerase chain reaction and immunohistochemistry. NY-ESO-1 expression and its distribution were furth er studied by immunohistochemistry in a tissue array contained 191 cases of HCC. Results NY-ESO-1 and LAGE-1 mRNAs were expressed in 33.3% (10/30) and 16.7 % (5/30) of HCC respectively. Either NY-ESO-1 or LAGE-1 was expressed in 36.7 % (11/30) cases. NY-ESO-1 was expressed mainly in the cytoplasm of tumor cells . It was positive in 13.8% (24/174) cases of HCC. There was an increased express ion of NY-ESO-1 from 6.8%, 3/44 in small HCC, 16.2%, 21/130 in advanced HCC an d 23.1%, 12/52 in metastatic HCC. The expression in the non-metastatic group wa s 9.8% (12/122). The differences between the metastatic group and non-metastati c group (P< 0.05) and between normal liver tissue and HCC (P< 0.01) were statistically significant. There was no relationship between NY-ESO-1 express ion and tumor size. NY-ESO-1 and LAGE-1 were not detected in adjacent normal liver tissue. Conclusions NY-ESO-1 and LAGE-1 are expressed in a high percentage of HCC, esp ecially in cases with metastasis. It is thus possible that NY-ESO-1/LAGE-1 ca n serve as targets for antigen-specific immunotherapy in HCC and NY-ESO-1 pep tide vaccination may be of use for patients with advanced HCC.