Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.
Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.
复制标题
人类生殖细胞肿瘤：γ-谷氨酰转肽酶的表达和对顺铂的敏感性。
DOI：
10.1038/sj.bjc.6690653
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发表时间：
1999
影响因子：
8.8
通讯作者：
TaylorJr,PT
中科院分区：
文献类型：
--
作者：
Hanigan,MH;FriersonJr,HF;Abeler,VM;Kaern,J;TaylorJr,PT
既往研究表明，γ-谷氨酰转肽酶（GGT）是顺铂肾毒性的关键酶。本研究旨在确定GGT活性是否是药物治疗效果所必需的。在41例人类生殖细胞肿瘤中研究了GGT表达与铂类化疗临床反应之间的关系。福尔马林固定、石蜡包埋的肿瘤切片用抗人GGT抗体进行免疫化学染色。在17例卵巢上皮瘤或4例无性细胞瘤中均无GGT表达，而12/12例卵巢卵黄囊瘤和4/4例睾丸胚胎性癌均为GGT阳性。在I期肿瘤中，表达GGT的肿瘤细胞比晚期肿瘤少。在四个生殖细胞肿瘤的混合组织学，腺瘤性和无性细胞瘤领域的GGT阴性，而卵黄囊或胚胎组织学的肿瘤区域包含GGT阳性的肿瘤细胞。接受以顺铂为基础的化疗的卵巢癌或无性细胞瘤患者，尽管在这些肿瘤中没有GGT表达，但都有完全缓解。16例卵黄囊癌或胚胎癌患者中有15例在手术后接受了以顺铂为基础的化疗。12例完全缓解，3例对铂类药物治疗无效。在该组中，GGT表达水平与治疗反应之间没有相关性。4例混合组织学肿瘤患者中有3例接受了以顺铂为基础的治疗，并获得了完全缓解。因此，GGT的表达对于顺铂在生殖细胞肿瘤中的治疗效果不是必需的。本研究的结果表明，全身抑制GGT可以抑制顺铂的肾毒性副作用，而不会干扰其对生殖细胞肿瘤的活性。
Previous studies have shown that the enzyme γ-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.