Heidenreich A, Kuczyk M, Albers P
Klinik und Poliklinik für Urologie, Universität Köln.
Urologe A. 1998 Nov;37(6):593-608. doi: 10.1007/s001200050222.
Aim of this review article was to critically analyse the recently described zytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosome i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (Cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromsomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in research for prognosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it also will define new approaches to classification and management of germ cell tumors.
这篇综述文章的目的是批判性地分析最近描述的睾丸生殖细胞肿瘤的细胞遗传学和分子标志物的临床实用性。等臂染色体i(12p)是最常见且具有特征性的细胞遗传学发现,在睾丸原位癌中就已出现。一些原癌基因(细胞周期蛋白D和甲状旁腺激素样蛋白)以及假定的肿瘤抑制基因定位于12p;然而,它们在睾丸生殖细胞肿瘤发病机制和预后中的作用尚未明确。家族性睾丸生殖细胞肿瘤患者的临床特征表明睾丸肿瘤的发生有遗传背景。尽管已经确定了一些编码潜在睾丸肿瘤易感基因的染色体位点,但睾丸癌发病机制的遗传基础仍然未知。关于分子预后危险因素,大多数已报道的关于增殖标志物、肿瘤抑制基因、蛋白酶和黏附分子的数据在广泛应用于临床之前,必须在前瞻性随机试验中得到证实。根据前瞻性研究的现有数据,胚胎癌的百分比和血管侵犯似乎是最显著的预后因素。研究和确定那些决定胚胎癌与所有其他组织学成分相比具有侵袭性生物学行为的因素,在转移性疾病预后因素的研究中似乎最有前景。总之,对睾丸生殖细胞肿瘤发病机制和预后中涉及的分子遗传事件的了解不断增加,不仅有助于更好地理解睾丸癌的发生和发展,还将为生殖细胞肿瘤的分类和管理确定新的方法。