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NY-ESO-1、MAGE-A3、PRAME 和 WT1 在不同乳腺癌亚组中的表达:免疫治疗的指征?

Expression of NY-ESO-1, MAGE-A3, PRAME and WT1 in different subgroups of breast cancer: An indication to immunotherapy?

机构信息

Department of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

出版信息

Breast. 2018 Dec;42:68-73. doi: 10.1016/j.breast.2018.08.106. Epub 2018 Aug 29.

Abstract

OBJECTIVES

Cancer Testis Antigens are immunogenic tumor-specific proteins. We investigated NY-ESO-1, MAGE-A3 and PRAME, in addition to WT1 expression in different Breast Cancer (BC) subtypes. We then evaluated the expression rate of NY-ESO-1 in early Triple Negative breast cancer (TNBC), and investigated whether its expression would be maintained or lost in the metastatic setting to explore possible immunotherapy indication.

MATERIALS AND METHODS

Three subgroups of BC patients were selected by the expression of ER, PgR and Her2. Tissue microarray was performed on a total of 92 Invasive BC. Sections were stained for NY-ESO-1, MAGE-A3, PRAME and WT1. The second cohort was composed by 26 metastatic TNBC patients from whom both the primary and secondary lesion tissues were available. Sections were stained for NY-ESO-1.

RESULTS

NY-ESO-1 was the only differentially expressed antigen and was absent in ER+ and ER-PgR + tumors, as for an exclusive expression of either NY-ESO-1 or at least one hormonal receptor (HR+). NY-ESO-1 was particularly represented in TNBC. No correlation has been found between MAGE-A3 and PRAME expression and subtype WT1 had low expression, except in the Her2+ group. In the second cohort, NY-ESO-1 was expressed in 12 and 24% of primary and metastatic lesions respectively.

CONCLUSIONS

This study defines a distinction between HR+ and HR-tumors through NY-ESO-1 expression. TNBC subgroup has the highest frequency of NY-ESO-1+ cases, and it could be the candidate population for the development of anti-NY-ESO-1 vaccine, both in the adjuvant or metastatic setting, and for the selection of cases suitable for immunotherapy.

摘要

目的

癌症睾丸抗原是免疫原性的肿瘤特异性蛋白。我们研究了 NY-ESO-1、MAGE-A3 和 PRAME,以及 WT1 在不同乳腺癌(BC)亚型中的表达。然后,我们评估了早期三阴性乳腺癌(TNBC)中 NY-ESO-1 的表达率,并研究了其在转移性环境中是否会保持或丢失,以探索可能的免疫治疗指征。

材料和方法

通过 ER、PgR 和 Her2 的表达,选择了三组 BC 患者。对总共 92 例浸润性 BC 进行组织微阵列分析。对 NY-ESO-1、MAGE-A3、PRAME 和 WT1 进行染色。第二队列由 26 例转移性 TNBC 患者组成,其中原发性和继发性病变组织均可用。对 NY-ESO-1 进行染色。

结果

NY-ESO-1 是唯一差异表达的抗原,在 ER+和 ER-PgR+肿瘤中不存在,因为仅表达 NY-ESO-1 或至少一种激素受体(HR+)。NY-ESO-1 在 TNBC 中特别表现。MAGE-A3 和 PRAME 表达与亚型之间没有相关性,WT1 表达较低,除了 Her2+组。在第二队列中,NY-ESO-1 在原发性和转移性病变中的表达率分别为 12%和 24%。

结论

本研究通过 NY-ESO-1 表达定义了 HR+和 HR-肿瘤之间的区别。TNBC 亚组中 NY-ESO-1+病例的频率最高,可能是开发抗 NY-ESO-1 疫苗的候选人群,无论是在辅助治疗还是转移性治疗环境中,以及为选择适合免疫治疗的病例。

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