NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors

NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors
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DOI:
10.1158/0008-5472.can-03-3070
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发表时间:
2004-03-15
期刊:
影响因子:
11.2
通讯作者:
Monden, M
Monden, M
中科院分区:
医学1区
文献类型:
--
作者:
Sugita, Y;Wada, H;Monden, M

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NY-ESO-1 是一种在正常成人组织中表达的癌症/睾丸抗原,仅在正常成人的睾丸生殖细胞和各种癌症中表达。它在表达 NY-ESO-1 的癌症患者中诱导特异性的不道德和细胞免疫。本研究的目的是确定恶性和良性乳腺肿瘤中 NY-ESO-1 mRNA 和蛋白表达的频率。通过常规逆转录PCR和实时PCR检测NY-ESO-1 mRNA表达,通过免疫组化和Western blot分析检测蛋白表达。在 88 份癌症标本中的 37 份 (42%) 中检测到 NY-ESO-1 mRNA 的表达,而 NY-ESO-1 蛋白的表达仅在 I mRNA 阳性标本中检测到。在后一种情况下,NY-ESO-1 mRNA 的表达水平相对于睾丸中的表达水平(睾丸表达的 75%)和乳腺癌样本中的其他表达水平相对较高。在良性乳腺病变中,31 个样本中的 21 个 (68%) 表达低水平的 NY-ESO-1 mRNA。 1例纤维腺瘤中NY-ESO-1 mRNA为睾丸水平的8%,Western blot分析检测到蛋白。只有一名乳腺癌患者在手术时可检测到抗体,该抗体在两年内消失。该患者的肿瘤标本均为 NY-ESO-1 mRNA 和蛋白阳性,并且使用 NY-ESO-1 重组腺病毒和牛痘病毒通过 IFN-γ 酶联免疫斑点测定法在该患者中检测到 NY-ESO-1 特异性 CD8 T 细胞。在组织学分级高且激素受体状态呈阴性的乳腺癌中,NY-ESO-1 表达率较高,表明 NY-ESO-1 作为乳腺癌患者免疫治疗的潜在肿瘤抗原,且预后不良。
NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific Immoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in I mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only I breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-gamma enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.