Madersbacher S, Kratzik C, Gerth R, Dirnhofer S, Berger P
Department of Urology, University of Vienna, Austria.
Cancer Res. 1994 Oct 1;54(19):5096-100.
To obtain insight into the secretion pattern of human chorionic gonadotropin (hCG) and its free subunits, hCG alpha and hCG beta, in vivo, we analyzed hydrocele fluids of 13 patients with testicular cancer and correlated the respective values to those of cubital vein and testicular vein serum. As a control population, patients with nonmalignant hydroceles (n = 11) were studied. Analyses were performed with a set of highly sensitive and specific time-resolved fluoroimmunoassays based on our own panel of monoclonal antibodies. In the collective of testicular cancer patients, increased hydrocele levels of either hCG or free hCG alpha or free hCG beta were observed in 77, 54, and 92% of cases; the corresponding percentages for cubital vein serum were 62, 23, and 31%. The cubital vein ratio of hCG:hCG alpha (546:1) and hCG:hCG beta (51:1) decreased to 64:1 and to 7:1 in the hydrocele fluids. Surprisingly, hydrocele fluids of five patients with pure seminoma, who were negative for the three markers in the periphery, revealed an elevation of free hCG beta in all cases, while hCG alpha and holo-hCG were elevated twice. Final proof that hCG beta and hCG alpha are indeed produced by these previously termed "marker negative" seminomas has been achieved by reverse transcriptase-polymerase chain reaction with primers specific for the alpha-subunit and the four most abundantly transcribed hCG beta genes 3, 5, 7, and 8. From these data, we conclude that: (alpha) seminomatous and nonseminomatous testicular cancers, irrespective of histology, secrete hCG and its free subunits; (b) the amount of free subunits being secreted in vivo by these tumors has been underestimated; and (c) the classification in marker-positive and marker-negative testicular cancer should be reconsidered.
为深入了解人绒毛膜促性腺激素（hCG）及其游离亚基hCGα和hCGβ在体内的分泌模式，我们分析了13例睾丸癌患者的鞘膜积液，并将各自的值与肘静脉和睾丸静脉血清的值进行关联。作为对照人群，研究了11例非恶性鞘膜积液患者。使用基于我们自己的单克隆抗体组的一组高度敏感和特异的时间分辨荧光免疫分析法进行分析。在睾丸癌患者群体中，77%、54%和92%的病例观察到鞘膜积液中hCG或游离hCGα或游离hCGβ水平升高；肘静脉血清的相应百分比分别为62%、23%和31%。鞘膜积液中hCG:hCGα（546:1）和hCG:hCGβ（51:1）的肘静脉比值分别降至64:1和7:1。令人惊讶的是，5例纯精原细胞瘤患者的鞘膜积液在外周血中这三种标志物均为阴性，但所有病例中游离hCGβ均升高，而hCGα和完整hCG升高了两倍。通过使用针对α亚基以及hCGβ的四个转录量最高的基因3、5、7和8的引物进行逆转录聚合酶链反应，最终证实了这些先前被称为“标志物阴性”的精原细胞瘤确实产生hCGβ和hCGα。根据这些数据，我们得出以下结论：（a）精原性和非精原性睾丸癌，无论组织学类型如何，均分泌hCG及其游离亚基；（b）这些肿瘤在体内分泌的游离亚基量被低估了；（c）应重新考虑睾丸癌标志物阳性和标志物阴性的分类。
