Abbas Mahmoud, Heitplatz Barbara, Bernemann Christof, Boegemann Martin, Trautmann Marcel, Schrader Andres Jan, Wardelmann Eva, Schlack Katrin
Department of Pathology, Prostate Center, University of Muenster Medical Center, D-48149 Muenster, Germany.
Department of Urology, Prostate Center, University of Muenster Medical Center, D-48149 Muenster, Germany.
Oncol Lett. 2023 Oct 23;26(6):527. doi: 10.3892/ol.2023.14114. eCollection 2023 Dec.
In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma , the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.
在转移性或局部晚期尿路上皮癌(UC)中,治疗选择一直局限于化疗和免疫检查点抑制剂。新型靶点和药物如抗体药物偶联物已被研发出来,靶向Nectin-4的恩杂鲁胺和靶向滋养层细胞表面抗原2(TROP-2,TACSTD2基因的蛋白质产物)的戈沙妥珠单抗(SG)已获批准。在UC和其他类型的癌症以及不同健康器官的组织中研究了TROP-2的表达,以了解治疗反应和毒性。回顾性分析了42例UC患者、13例其他类型癌症患者的组织以及11例患者正常组织中TROP-2的表达。根据认可的染色方案,在德国明斯特大学医院病理研究所(格哈德·多马克研究所)免疫组织化学实验室的常规免疫组织化学认可和认证设施中,使用BenchMark ULTRA IHC/ISH系统(罗氏组织诊断;罗氏诊断有限公司)对TROP-2蛋白进行免疫组织化学染色。观察到TROP-2有不同的表达水平,且在UC中观察到TROP-2的最高表达率,与肿瘤分期无关。然而,正常尿路上皮细胞的表达水平相似。除导管癌外,在其他类型的癌症以及包括胰腺、胆囊、结肠和前列腺在内的其他器官的健康组织中,TROP-2的表达降低。鉴于基于TROP-2表达水平的治疗反应,SG在几乎所有UC病例中都将有效。然而,它也会对正常尿路上皮产生影响。