Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
Hum Pathol. 2013 Oct;44(10):2312-22. doi: 10.1016/j.humpath.2013.05.013. Epub 2013 Aug 9.
Among adult testicular germ cell tumors, the pathogenesis of embryonal carcinoma remains a matter of debate. Some studies suggest a single consecutive progression from intratubular germ cell neoplasia, unclassified (IGCNU), to seminoma and then to embryonal carcinoma; others suggest that seminoma and embryonal carcinoma derive independently from IGCNU. This allelotyping study aimed to clarify the genetic relationship between embryonal carcinoma components and coexisting seminoma and/or IGCNU components. From a cohort of 18 patients with embryonal carcinoma, 11 coexisting seminoma components and 14 coexisting IGCNUs were identified. DNA isolated from each laser-microdissected tissue was subjected to polymerase chain reaction and loss of heterozygosity (LOH) analysis, using 20 polymorphic markers located on 12 chromosome arms (3q, 5q, 6p, 9p, 10q, 11p, 12p, 12q, 13q, 17p, 17q, and 18q). The concordance rate for allelic patterns was 82% between IGCNU and the coexisting seminoma components, 71% between IGCNU and the coexisting embryonal carcinoma components, and 80% between seminoma components and the coexisting embryonal carcinoma components. Estimation of probability indicated that these events were very unlikely to have occurred by chance. The total frequency of LOH increased progressively from IGCNU to seminoma and then to embryonal carcinoma, with statistically significant differences. In 7 cases with 3 histologic components, 28 chromosomal loci that showed LOH in the seminoma and embryonal carcinoma components were identified, and 15 (54%) retained heterozygosity in the coexisting IGCNUs. These findings suggest that a consecutive progression from IGCNU to seminoma, and ultimately, to embryonal carcinoma mainly occurred in the testicular germ cell tumor cases.
在成人睾丸生殖细胞肿瘤中，胚胎癌的发病机制仍存在争议。一些研究表明，从小管内生殖细胞肿瘤，未分类（IGCNU），到精原细胞瘤，然后到胚胎癌，存在单一的连续进展；另一些研究则表明精原细胞瘤和胚胎癌是从 IGCNU 独立衍生而来的。这项基因分型研究旨在阐明胚胎癌成分与共存的精原细胞瘤成分和/或 IGCNU 成分之间的遗传关系。从 18 例胚胎癌患者中，鉴定出 11 例共存的精原细胞瘤成分和 14 例共存的 IGCNU。从每个激光微切割组织中分离出的 DNA ，用 20 个位于 12 条染色体臂上的多态性标记物（3q、5q、6p、9p、10q、11p、12p、12q、13q、17p、17q 和 18q）进行聚合酶链反应和杂合性丢失（LOH）分析。IGCNU 与共存的精原细胞瘤成分之间的等位基因模式一致性率为 82%，IGCNU 与共存的胚胎癌成分之间为 71%，精原细胞瘤成分与共存的胚胎癌成分之间为 80%。概率估计表明，这些事件不太可能是偶然发生的。LOH 的总频率从 IGCNU 到精原细胞瘤，然后到胚胎癌逐渐增加，差异具有统计学意义。在 7 例具有 3 种组织学成分的病例中，在精原细胞瘤和胚胎癌成分中显示 LOH 的 28 个染色体位点被鉴定出来，其中 15 个（54%）在共存的 IGCNU 中保留了杂合性。这些发现表明，IGCNU 向精原细胞瘤，最终向胚胎癌的连续进展主要发生在睾丸生殖细胞肿瘤病例中。
