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Published in: Virchows Archiv 6/2019

01-06-2019 | Seminoma | Original Article

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

Authors: Kosuke Miyai, Keiichi Ito, Kuniaki Nakanishi, Hitoshi Tsuda

Published in: Virchows Archiv | Issue 6/2019

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Abstract

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.
Literature
1.
go back to reference Mostofi FK, Sesterhenn IA (2016) Germ cell tumours. Tumours of the testis and paratesticular tissue. In: Mock H, Humphrey PA, Ulbright TM, Reuter VE (eds) WHO classification of tumours of the urinary system and male genital organs. IARC press, Lyon, pp 189–226 Mostofi FK, Sesterhenn IA (2016) Germ cell tumours. Tumours of the testis and paratesticular tissue. In: Mock H, Humphrey PA, Ulbright TM, Reuter VE (eds) WHO classification of tumours of the urinary system and male genital organs. IARC press, Lyon, pp 189–226
2.
go back to reference Jacobsen GK, Barlebo H, Olsen HJ, Schultz HP, Starklint H, Søgaard H, Vaeth M (1984) Testicular germ cell tumours in Denmark 1976–1980 pathology of 1058 consecutive cases. Acta Radiol Oncol 23:239–247CrossRef Jacobsen GK, Barlebo H, Olsen HJ, Schultz HP, Starklint H, Søgaard H, Vaeth M (1984) Testicular germ cell tumours in Denmark 1976–1980 pathology of 1058 consecutive cases. Acta Radiol Oncol 23:239–247CrossRef
3.
go back to reference Bosl GJ, Motzer RJ (1997) Medical progress: testicular germ-cell cancer. N Engl J Med 337:242–253CrossRefPubMed Bosl GJ, Motzer RJ (1997) Medical progress: testicular germ-cell cancer. N Engl J Med 337:242–253CrossRefPubMed
5.
go back to reference Skakkebaek NE, Berthelsen JG, Giwercman A, Müller J (1987) Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 10:19–28CrossRefPubMed Skakkebaek NE, Berthelsen JG, Giwercman A, Müller J (1987) Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 10:19–28CrossRefPubMed
7.
go back to reference Oosterhuis JW, Looijenga LH (1993) The biology of human germ cell tumours: retrospective speculations and new prospectives. Eur Urol 23:245–250CrossRefPubMed Oosterhuis JW, Looijenga LH (1993) The biology of human germ cell tumours: retrospective speculations and new prospectives. Eur Urol 23:245–250CrossRefPubMed
11.
go back to reference van Echten J, Oosterhuis JW, Looijenga LH, van de Pol M, Wiersema J, te Meerman GJ, Schaffordt Koops H, Sleijfer DT, de Jong B (1995) No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes Chromosomes Cancer 14:133–144CrossRefPubMed van Echten J, Oosterhuis JW, Looijenga LH, van de Pol M, Wiersema J, te Meerman GJ, Schaffordt Koops H, Sleijfer DT, de Jong B (1995) No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes Chromosomes Cancer 14:133–144CrossRefPubMed
13.
go back to reference Mostert MM, van de Pol M, Olde Weghuis D, Suijkerbuijk RF, Geurts van Kessel A, van Echten J, Oosterhuis JW, Looijenga LH (1996) Comparative genomic hybridization of germ cell tumors of the adult testis: confirmation of karyotypic findings and identification of a 12p-amplicon. Cancer Genet Cytogenet 89:146–152CrossRefPubMed Mostert MM, van de Pol M, Olde Weghuis D, Suijkerbuijk RF, Geurts van Kessel A, van Echten J, Oosterhuis JW, Looijenga LH (1996) Comparative genomic hybridization of germ cell tumors of the adult testis: confirmation of karyotypic findings and identification of a 12p-amplicon. Cancer Genet Cytogenet 89:146–152CrossRefPubMed
14.
go back to reference Sandberg AA, Meloni AM, Suijkerbuijk RF (1996) Reviews of chromosome studies in urological tumors. III Cytogenetics and genes in testicular tumors. J Urol 155:1531–1556CrossRefPubMed Sandberg AA, Meloni AM, Suijkerbuijk RF (1996) Reviews of chromosome studies in urological tumors. III Cytogenetics and genes in testicular tumors. J Urol 155:1531–1556CrossRefPubMed
15.
go back to reference Summersgill BM, Jafer O, Wang R, Goker H, Niculescu-Duvaz I, Huddart R, Shipley J (2001) Definition of chromosome aberrations in testicular germ cell tumor cell lines by 24-color karyotyping and complementary molecular cytogenetic analyses. Cancer Genet Cytogenet 128:120–129CrossRefPubMed Summersgill BM, Jafer O, Wang R, Goker H, Niculescu-Duvaz I, Huddart R, Shipley J (2001) Definition of chromosome aberrations in testicular germ cell tumor cell lines by 24-color karyotyping and complementary molecular cytogenetic analyses. Cancer Genet Cytogenet 128:120–129CrossRefPubMed
17.
go back to reference Brimo F, Srigley JR, Ryan CJ, Choyke PL, Humphrey PA, Barocas DA, Brookland RK, Buyyounouski MK, Fine SW, Halabi S, Hamstra DA, Kattan MW, McKenney JK, Mason MD, Oh WK, Pettaway CA, Touijer KA, Zelefsky MJ, Sandler HM, Amin MB, Lin DW (2017) Testis. In: Amin MB, Edge S, Greene F et al (eds) AJCC cancer staging manual, 8th edn. Springer International publishing, New York, pp 727–735 Brimo F, Srigley JR, Ryan CJ, Choyke PL, Humphrey PA, Barocas DA, Brookland RK, Buyyounouski MK, Fine SW, Halabi S, Hamstra DA, Kattan MW, McKenney JK, Mason MD, Oh WK, Pettaway CA, Touijer KA, Zelefsky MJ, Sandler HM, Amin MB, Lin DW (2017) Testis. In: Amin MB, Edge S, Greene F et al (eds) AJCC cancer staging manual, 8th edn. Springer International publishing, New York, pp 727–735
18.
go back to reference Tsuda H, Akiyama F, Terasaki H, Hasegawa T, Kurosumi M, Shimadzu M, Yamamori S, Sakamoto G (2001) Detection of HER-2/neu (c-erb B-2) DNA amplification in primary breast carcinoma. Interobserver reproducibility and correlation with immunohistochemical HER-2 overexpression. Cancer 92:2965–2974CrossRefPubMed Tsuda H, Akiyama F, Terasaki H, Hasegawa T, Kurosumi M, Shimadzu M, Yamamori S, Sakamoto G (2001) Detection of HER-2/neu (c-erb B-2) DNA amplification in primary breast carcinoma. Interobserver reproducibility and correlation with immunohistochemical HER-2 overexpression. Cancer 92:2965–2974CrossRefPubMed
19.
go back to reference Lengauer C, Kinzler KW, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623–627CrossRefPubMed Lengauer C, Kinzler KW, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623–627CrossRefPubMed
21.
go back to reference Stebbins GL (1947) Types of polyploids: their classification and significance. Adv Genet 1:403–429CrossRefPubMed Stebbins GL (1947) Types of polyploids: their classification and significance. Adv Genet 1:403–429CrossRefPubMed
25.
go back to reference de Graaff WE, Oosterhuis JW, de Jong B, Dam A, van Putten WL, Castedo SM, Sleijfer DT, Schraffordt Koops H (1992) Ploidy of testicular carcinoma in situ. Lab Investig 66:166–168PubMed de Graaff WE, Oosterhuis JW, de Jong B, Dam A, van Putten WL, Castedo SM, Sleijfer DT, Schraffordt Koops H (1992) Ploidy of testicular carcinoma in situ. Lab Investig 66:166–168PubMed
27.
go back to reference Looijenga LH, Gillis AJ, Van Putten WL, Oosterhuis JW (1993) In situ numeric analysis of centromeric regions of chromosomes 1, 12, and 15 of seminomas, nonseminomatous germ cell tumors, and carcinoma in situ of human testis. Lab Investig 68:211–219PubMed Looijenga LH, Gillis AJ, Van Putten WL, Oosterhuis JW (1993) In situ numeric analysis of centromeric regions of chromosomes 1, 12, and 15 of seminomas, nonseminomatous germ cell tumors, and carcinoma in situ of human testis. Lab Investig 68:211–219PubMed
31.
go back to reference Igarashi S, Suzuki H, Niinuma T, Shimizu H, Nojima M, Iwaki H, Nobuoka T, Nishida T, Miyazaki Y, Takamaru H, Yamamoto E, Yamamoto H, Tokino T, Hasegawa T, Hirata K, Imai K, Toyota M, Shinomura Y (2010) A novel correlation between LINE-1 hypomethylation and the malignancy of gastrointestinal stromal tumors. Clin Cancer Res 16:5114–5123. https://doi.org/10.1158/1078-0432.CCR-10-0581 CrossRefPubMed Igarashi S, Suzuki H, Niinuma T, Shimizu H, Nojima M, Iwaki H, Nobuoka T, Nishida T, Miyazaki Y, Takamaru H, Yamamoto E, Yamamoto H, Tokino T, Hasegawa T, Hirata K, Imai K, Toyota M, Shinomura Y (2010) A novel correlation between LINE-1 hypomethylation and the malignancy of gastrointestinal stromal tumors. Clin Cancer Res 16:5114–5123. https://​doi.​org/​10.​1158/​1078-0432.​CCR-10-0581 CrossRefPubMed
Metadata
Title
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
Authors
Kosuke Miyai
Keiichi Ito
Kuniaki Nakanishi
Hitoshi Tsuda
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 6/2019
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-019-02560-6

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