Tolkach Yuri, Goltz Diane, Kremer Anika, Ahmadzadehfar Hojjat, Bergheim Dominik, Essler Markus, Lam Marnix, de Keizer Bart, Fischer Hans-Peter, Kristiansen Glen
Institute of Pathology, University Hospital Bonn, Bonn 53127, Germany.
Clinic of Nuclear Medicine, University Hospital Bonn, Bonn 53127, Germany.
Oncotarget. 2019 Jun 25;10(41):4149-4160. doi: 10.18632/oncotarget.27024.
The prostate-specific membrane antigen (PSMA) is currently being established as a potent diagnostic marker in many tumor types. So far, its evidence in hepatocellular carcinoma (HCC) is sparse. The aim of our study was a comprehensive evaluation of PSMA expression and its prognostic role in patients with hepatocellular carcinoma as well as feasibility test of PSMA as an agent for diagnostic imaging.
The cohort for immunohistochemistry consisted of 153 patients with HCC. For validation purposes the HCC cohort (n = 359) of The Cancer Genome Atlas was analyzed on transcript level as well.
On immunohistochemistry, non-tumorous liver tissue showed PSMA expression on canalicular membranes in all cases. In tumor tissue two patterns of expression, with a canalicular (41.1% of tumors) and a neovascular (89.9% of tumors) staining were seen. Completely negative for both two patterns were only 4.1% of tumors; conversely, 79.2% of the tumors showed high levels of PSMA protein expression at any location. At mRNA level higher (PSMA) expression rates were statistically significant and independently associated with longer overall survival times.Additionally, a case report of successful diagnostic Ga-PSMA-11 PET/CT in a patient with HCC progression on multiple therapy lines is provided.
Majority of hepatocellular carcinomas show high levels of PSMA expression on tumor vessels and on canalicular membrane of the tumor cells. Putative diagnostic, prognostic and therapeutic value of PSMA in HCC warrants further clinically oriented investigations.
前列腺特异性膜抗原（PSMA）目前正被确立为多种肿瘤类型的有效诊断标志物。到目前为止，其在肝细胞癌（HCC）中的证据还很少。我们研究的目的是全面评估PSMA在肝细胞癌患者中的表达及其预后作用，以及PSMA作为诊断成像剂的可行性测试。
免疫组织化学队列包括153例HCC患者。为了进行验证，还对癌症基因组图谱的HCC队列（n = 359）进行了转录水平分析。
免疫组织化学显示，非肿瘤性肝组织在所有病例的胆小管膜上均有PSMA表达。在肿瘤组织中，观察到两种表达模式，即胆小管染色（41.1%的肿瘤）和新生血管染色（89.9%的肿瘤）。仅4.1%的肿瘤两种模式均完全阴性；相反，79.2%的肿瘤在任何位置均显示高水平的PSMA蛋白表达。在mRNA水平上，较高的（PSMA）表达率具有统计学意义，且与较长的总生存时间独立相关。此外，还提供了一例在接受多种治疗方案后HCC进展患者中成功进行Ga-PSMA-11 PET/CT诊断的病例报告。
大多数肝细胞癌在肿瘤血管和肿瘤细胞的胆小管膜上显示高水平的PSMA表达。PSMA在HCC中的潜在诊断、预后和治疗价值值得进一步开展以临床为导向的研究。
