Stephan Alexa, Kotthoff Mara, Bremmer Felix, Nettersheim Daniel
Klinik für Urologie, Urologisches Forschungslabor, Translationale UroOnkologie, Medizinische Fakultät und Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Deutschland.
Institut für Pathologie, Universitätsmedizin Göttingen, Göttingen, Deutschland.
Pathologie (Heidelb). 2022 Nov;43(6):409-415. doi: 10.1007/s00292-022-01094-0. Epub 2022 Aug 1.
Germ cell tumors (GCTs) are the most common type of cancer in Germany in young men between 15 and 44 years of age. The routinely performed diagnostic procedures are essential for the patient's treatment, but can be difficult due to heterogenous histologies. Additionally, the molecular mechanisms of the development of the special forms growing teratoma syndrome (GTS) and testicular tumors with malignant somatic transformation (MST) as well as of therapy resistance are not fully understood.
Updated understanding of the molecular processes underlying GCT development and their special forms as well as recommendations for new and useful biomarkers.
The development of GCTs is a dynamic process largely influenced by the microenvironment. Seminomas (SEs) in particular seem to posses a higher cellular plasticity than previously assumed, allowing SEs to be reprogrammed into an embryonal carcinoma (EC) or differentiate into extra-embryonal tissues (yolk sac tumors [YSTs], trophoblastic differentiation). Novel serological (mi371a-3p) and pathological (FOXA2) biomarkers are well suited to early detect GCTs and YSTs, respectively. For more aggressive tumors and special cases (GTS, MST), there are still no reliable diagnostics or specific/tailored therapies available.
The ability of SEs to transit into EC or YSTs should be considered during therapy. Future research should focus on deciphering the special forms GTS and MST as well as the early recognition of YSTs, since their development seems to be an escape mechanism to chemotherapy.
生殖细胞肿瘤(GCTs)是德国15至44岁年轻男性中最常见的癌症类型。常规进行的诊断程序对患者的治疗至关重要,但由于组织学异质性,可能会有困难。此外,生长性畸胎瘤综合征(GTS)和伴有恶性体细胞转化(MST)的睾丸肿瘤以及治疗耐药性的特殊形式的分子机制尚未完全了解。
更新对GCT发展及其特殊形式的分子过程的认识,以及对新的和有用的生物标志物的建议。
GCT的发展是一个很大程度上受微环境影响的动态过程。特别是精原细胞瘤(SEs)似乎具有比以前认为的更高的细胞可塑性,使得SEs能够重新编程为胚胎癌(EC)或分化为胚外组织(卵黄囊瘤[YSTs],滋养层分化)。新的血清学(mi371a-3p)和病理学(FOXA2)生物标志物分别非常适合早期检测GCT和YST。对于更具侵袭性的肿瘤和特殊情况(GTS,MST),仍然没有可靠的诊断方法或特定/定制的治疗方法。
在治疗过程中应考虑SEs转变为EC或YST的能力。未来的研究应集中在破译GTS和MST的特殊形式以及YST的早期识别上,因为它们的发展似乎是化疗的一种逃逸机制。