Odunsi Kunle, Jungbluth Achim A, Stockert Elisabeth, Qian Feng, Gnjatic Sacha, Tammela Jonathan, Intengan Marilyn, Beck Amy, Keitz Bernadette, Santiago Darren, Williamson Barbara, Scanlan Matthew J, Ritter Gerd, Chen Yao-Tseng, Driscoll Deborah, Sood Ashwani, Lele Shashikant, Old Lloyd J
Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Res. 2003 Sep 15;63(18):6076-83.
Cancer-testis (CT) antigens are expressed in a variety of cancers, but not in normal adult tissues, except for germ cells of the testis, and hence appear to be ideal targets for immunotherapy. In an effort to examine the potential of NY-ESO-1 and LAGE-1 CT antigens for immunotherapy in epithelial ovarian cancer (EOC), we examined the expression of these antigens by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC) in a large panel of EOC tissues and cell lines. Sera from a subgroup of the patients were tested for NY-ESO-1/LAGE-1 antibody by ELISA. The data indicated that four ovarian cancer cell lines were positive for one or both CT antigens. Expression of NY-ESO-1 in EOC was demonstrated by RT-PCR and/or IHC in 82 of 190 (43%) specimens. NY-ESO-1 expression by IHC ranged from homogeneous to heterogeneous pattern. LAGE-1 mRNA expression was present in 22 of 107 (21%) tumor tissues. Overall, the expression of either NY-ESO-1 or LAGE-1 mRNA was present in 42 of 107 (40%) EOC specimens and coexpression of both antigens was demonstrated in 11% of specimens. Antibody to NY-ESO-1/LAGE-1 was present in 11 of 37 (30%) patients whose tumors expressed either NY-ESO-1 or LAGE-1. Detectable antibodies were present for up to 3 years after initial diagnosis. Although there was no statistically significant relation between expression of NY-ESO-1/LAGE-1 antigen and survival, the data showed aberrant expression of NY-ESO-1 and LAGE-1 by IHC/RT-PCR in a significant proportion of EOC patients. These findings indicate that NY-ESO-1 and LAGE-1 are attractive targets for antigen-specific immunotherapy in EOC.
癌-睾丸（CT）抗原在多种癌症中表达，但在正常成人组织中不表达，睾丸生殖细胞除外，因此似乎是免疫治疗的理想靶点。为了研究NY-ESO-1和LAGE-1 CT抗原在上皮性卵巢癌（EOC）免疫治疗中的潜力，我们通过逆转录-聚合酶链反应（RT-PCR）和免疫组织化学（IHC）检测了一大组EOC组织和细胞系中这些抗原的表达。通过酶联免疫吸附测定（ELISA）检测了部分患者亚组的血清中NY-ESO-1/LAGE-1抗体。数据表明，四种卵巢癌细胞系对一种或两种CT抗原呈阳性。RT-PCR和/或IHC显示，190例标本中有82例（43%）的EOC中存在NY-ESO-1表达。免疫组化显示NY-ESO-1表达从均匀到不均匀。107例肿瘤组织中有22例（21%）存在LAGE-1 mRNA表达。总体而言，107例EOC标本中有42例（40%）存在NY-ESO-1或LAGE-1 mRNA表达，11%的标本中两种抗原共表达。37例肿瘤表达NY-ESO-1或LAGE-1的患者中有11例（30%）存在NY-ESO-1/LAGE-1抗体。初次诊断后长达3年可检测到抗体。虽然NY-ESO-1/LAGE-1抗原表达与生存率之间无统计学显著关系，但数据显示，相当一部分EOC患者通过免疫组化/RT-PCR检测到NY-ESO-1和LAGE-1表达异常。这些发现表明，NY-ESO-1和LAGE-1是EOC抗原特异性免疫治疗的有吸引力的靶点。
