Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases
Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases
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DOI：
10.1007/s10585-018-9878-x
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Juhasz-Boess, Ingolf
中科院分区：
文献类型：
--
作者：
Kasoha, Mariz;Unger, Clara;Juhasz-Boess, Ingolf
本研究旨在探讨前列腺特异性膜抗原（PSMA）在正常乳腺组织、癌性乳腺组织和乳腺癌远处转移患者中的表达。分别使用抗PSMA单抗和抗cd31单抗进行免疫组化分析，检测PSMA的表达和血管生成活性。免疫荧光染色证实PSMA和CD31的确切共定位。我们观察到PSMA在正常组织和癌组织中的表达模式不同。正常乳腺组织中PSMA仅在正常腺细胞中表达。然而，原发性乳腺肿瘤和远处转移瘤在肿瘤细胞和肿瘤相关的新生血管中均有PSMA表达。原发性乳腺肿瘤PSMA评分组状态与组织学分型、肿瘤分级显著相关（p = 0.026、p = 0.004）。与原发肿瘤相比，远处转移的肿瘤相关血管中PSMA的表达更高。此外，与骨肿瘤相关的新培养相比，脑肿瘤相关的新培养具有显著更高的PSMA表达。双免疫荧光染色证实PSMA单抗与新生血管内皮的局部结合。一名转移性乳腺癌患者的Ga-68-PSAM成像显示，所有已知的骨骼转移灶都有很强的示踪剂摄取。据我们所知，这项研究是第二项在大量乳腺癌患者中评估PSMA表达的研究。我们的研究结果表明，PSMA在乳腺肿瘤及其远处转移的肿瘤相关血管系统中特别表达，从而增强了PSMA作为治疗血管靶点的潜在有效性的证据。
The present study was undertaken to investigate the expression of prostate-specific membrane antigen (PSMA) in normal breast tissues, in cancerous breast tissues and in distant metastases from patients with breast cancer. Immunohistochemical analysis was performed to determine PSMA expression and angiogenic activity using anti-PSMA mAb and anti-CD31 mAb respectively. Immunofluorescence staining was applied to confirm the exact co-localization of PSMA and CD31. We observed different patterns of PSMA expression between normal and cancerous tissues. Normal breast tissues showed PSMA expression only in normal glandular cells. However, primary breast tumors and distant metastases showed PSMA expression in tumor cells and in tumor-associated neovasculature. PSMA score group status in primary breast tumors was significantly associated with histologic type and tumor grade (p = 0.026 and p = 0.004 respectively). Distant metastases showed higher PSMA expression in tumor-associated neovasculature comparing with primary tumors. Moreover, brain tumor-associated neovasculture had significantly higher expression of PSMA comparing with bone tumor-associated neovasculture. The localized binding of PSMA mAb to the neovasculature endothelium was confirmed with the double Immunofluorescence staining. Ga-68-PSAM imaging of a patient with metastatic breast cancer showed strong tracer uptake in all known skeletal metastases. To the best of our knowledge, this study is the second one that has assessed PSMA expression in a large number of breast cancer patients. Our findings showed that PSMA is particularly expressed in tumor-associated neovasculature of breast tumors and its distant metastases, thus enhancing the evidence on the potential usefulness of PSMA as a therapeutic vascular target.