Dieckmann Klaus-Peter, Belge Gazanfer
Urologie, Asklepios Klinik Altona, Hamburg, Germany.
Universität Bremen, Institut für Tumordiagnostik, Bremen, Germany.
Aktuelle Urol. 2024 Dec;55(6):510-519. doi: 10.1055/a-2358-8355. Epub 2024 Aug 12.
Testicular germ cell tumours (GCTs) represent a paradigm for the usefulness of serum tumour markers in clinical management of diseases. However, the tumour markers currently in use, beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) are expressed in less than 50% of GCT cases. In 2011, microRNA-371a-3p (currently named M371) was suggested as a novel marker for the first time. Chemically, microRNAS represent small RNA molecules consisting of 18-24 base pairs. Physiologically, these microRNAs play a prominent role in the epigenetic control of protein biosynthesis. M371 can be measured in serum with PCR-techniques.There is high level evidence for a 90% sensitivity and >90% specificity for GCTs of the marker M371. That high diagnostic accuracy is true for both seminoma and nonseminoma but not for the histologic subgroup of teratoma. Testicular tumours of non-germ cell origin and malignant neoplasms of other organs do not express the marker. M371 involves a very short half-life of <24 hours.The test does likely involve the prospects of providing substantial aid in clinical decision-making with respect to instances where improvement of GCT management is still required. In particular, the following clinical scenarios will probably benefit from the employment of the M371 test: (1) diagnostic work-up of incidentally detected small testicular masses with decision-making in regard to testis sparing surgery or full orchiectomy (2) simplifying the follow-up of GCT patients with sparing of imaging procedures in a number of cases; (3) diagnostic evaluation of retroperitoneal lymphadenopathy upon clinical staging; (4) diagnostic evaluation of false-positive elevations of classical tumour markers (AFP, bHCG); (5) rapid appraisal of therapeutic success or failure by means of the very short half-life of M371; (6) diagnostic evaluation of postchemotherapy residual masses particularly those in seminoma patients.The discovery and development of the novel tumour marker M371 probably represents a milestone progress in the history of the clinical management of testicular GCTs.
睾丸生殖细胞肿瘤(GCTs)是血清肿瘤标志物在疾病临床管理中发挥作用的一个范例。然而,目前使用的肿瘤标志物,β人绒毛膜促性腺激素(bHCG)、甲胎蛋白(AFP)和乳酸脱氢酶(LDH),在不到50%的GCT病例中表达。2011年,首次提出将微小RNA-371a-3p(现称为M371)作为一种新型标志物。从化学角度来看,微小RNA是由18 - 24个碱基对组成的小RNA分子。从生理角度而言,这些微小RNA在蛋白质生物合成的表观遗传控制中发挥着重要作用。M371可以通过PCR技术在血清中进行检测。有高水平证据表明,该标志物M371对GCTs的敏感性为90%,特异性>90%。这种高诊断准确性对于精原细胞瘤和非精原细胞瘤均适用,但对于畸胎瘤的组织学亚组则不然。非生殖细胞起源的睾丸肿瘤和其他器官的恶性肿瘤不表达该标志物。M371的半衰期非常短,小于24小时。该检测在改善GCT管理仍有需求的情况下,确实可能有助于在临床决策中提供实质性帮助。特别是,以下临床情况可能会受益于M371检测的应用:(1)对偶然发现的小睾丸肿块进行诊断性检查,以决定进行保留睾丸手术还是全睾丸切除术;(2)在许多情况下简化GCT患者的随访,减少成像检查;(3)在临床分期时对腹膜后淋巴结肿大进行诊断评估;(4)对经典肿瘤标志物(AFP、bHCG)的假阳性升高进行诊断评估;(5)通过M371非常短的半衰期快速评估治疗成功或失败;(6)对化疗后残留肿块进行诊断评估,尤其是精原细胞瘤患者中的残留肿块。新型肿瘤标志物M371的发现和开发可能代表了睾丸GCTs临床管理史上的一个里程碑式进展。