Cell-to-cell variation of chromosomal number in the adult testicular germ cell tumors: a comparison of chromosomal instability among histological components and its putative role in tumor progression

  • Kosuke MiyaiEmail author
  • Keiichi Ito
  • Kuniaki Nakanishi
  • Hitoshi Tsuda
Original Article


By allelotyping analysis, we previously reported a putative progression pathway from germ cell neoplasia in situ (GCNIS) to seminoma, then to embryonal carcinoma in mixed-type testicular germ cell tumors (TGCTs), and detected that loss of heterozygosity events in seminoma components in mixed tumors were more frequent than those in pure seminomas. To elucidate a role of chromosomal instability in the progression of non-seminomatous germ cell tumor (NSGCT), we performed fluorescence in situ hybridization with centromeric probes for chromosomes 1, 7, 8, 12, 17, and X on a cohort of 52 TGCT cases with 103 histologically distinct components: 39 GCNIS lesions (16 and 23 in tumors with and without NSGCT components, respectively), 39 seminomas (27 as pure seminomas and 12 in mixed tumors), and 25 embryonal carcinomas. On a total component basis, both the mean copy number per tumor cell nucleus and the deviations from the modal number of all chromosomes examined significantly increased from GCNIS to seminoma, then to embryonal carcinoma with few exceptions. Seminoma components in mixed tumors showed a significantly greater extent of chromosomal instability in chromosomes 8 and 12 than pure seminomas, whereas no statistically significant difference was observed between GCNIS lesions with and without NSGCT components. These results suggest that not only aneuploidy, but also the cell-to-cell variation of chromosomal number is a sensitive indicator of chromosomal instability and would be implicated in the progression of NSGCT.


Testis Germ cell tumor Chromosomal instability Fluorescence in situ hybridization 


Authors’ contributions

K.M. collected the clinical patient data, examined histopathological findings, performed the experiments (FISH), evaluated the FISH data, analyzed the data, participated in the study design, and wrote the manuscript. K.I. assisted in clinical data acquisition, histopathological examination, and revised the manuscript. K.N. stimulated the study, provided the reference pathology for all the samples used, and revised the manuscript. H.T. conceived the study, analyzed the data, and drafted and revised the manuscript.

Funding information

This work was supported in part by a grant-in-aid for the Promotion of Defense Medicine from the Ministry of Defense, Japan (K.M., H.T.).

Compliance with ethical standards

All patients gave informed consent for retention and anonymous analysis of their tissue for research purposes in accordance with the requirements of the ethical committee of the National Defense Medical College (Approval No. 168).

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Basic PathologyNational Defense Medical CollegeTokorozawaJapan
  2. 2.Department of Laboratory MedicineNational Defense Medical CollegeTokorozawaJapan
  3. 3.Department of UrologyNational Defense Medical CollegeTokorozawaJapan

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