Skip to main content
Log in

Consistent numerical chromosome aberrations in thecofibromas of the ovary

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Sex cord-stromal tumors of the ovary comprise 8% of all ovarian neoplasms. Because they consist of cells that resemble embryonic sex cord and/or specialized ovarian stroma cells, their cytologic and histologic features can be viewed as reflecting a continuum from fibromas to thecomas with thecofibromas in between. Existing cytogenetic knowledge about ovarian thecomas–thecofibromas–fibromas is restricted to 44 cases with chromosomal abnormalities. The most common aberration has been trisomy 12, identified either by karyotyping or using fluorescence in situ hybridization (FISH). We wanted to obtain more information about the genomic composition of these tumors, and, therefore, examined 29 new thecoma–thecofibroma–fibroma tumors of the ovary using karyotyping, comparative genomic hybridization, interphase FISH, and DNA ploidy analysis. We detected aneuploidy in 21 tumors. Trisomy and/or tetrasomy 12 was the most common chromosomal aberration, found in 15 tumors (71.5% of the aneuploid tumors or 51.5% of all analyzed tumors), followed by trisomy for chromosomes 10, 18, 4, and 9. Some monosomies (for chromosomes 4, 9, 10, and 18) were also identified, either as the sole change or in combination with trisomies. The nonrandom occurrence of these aneuploidies in these benign tumors strongly indicates that they play a major pathogenetic role, but how trisomies and other aneuploidies contribute to tumorigenesis remains unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bown N, Cotterill SJ, Roberts P, Griffiths M, Larkins S, Hibbert S, Middleton H, Kelsey A, Tritton D, Mitchell C (2002) Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children’s Cancer Study Group. Med Pediatr Oncol 38:11–21

    Article  PubMed  Google Scholar 

  2. Brandal P, Bjerkehagen B, Heim S (2004) Molecular cytogenetic characterization of tenosynovial giant cell tumors. Neoplasia 6:578–583

    Article  PubMed  CAS  Google Scholar 

  3. Fletcher JA, Gibas Z, Donovan K, Perez-Atayde A, Genest D, Morton CC, Lage JM (1991) Ovarian granulosa-stromal cell tumors are characterized by trisomy 12. Am J Pathol 138:515–520

    PubMed  CAS  Google Scholar 

  4. Garcia-Marco JA, Price CM, Ellis J, Morey M, Matutes E, Lens D, Colman S, Catovsky D (1996) Correlation of trisomy 12 with proliferating cells by combined immunocytochemistry and fluorescence in situ hybridization in chronic lymphocytic leukemia. Leukemia 10:1705–1711

    PubMed  CAS  Google Scholar 

  5. Geisler CH, Philip P, Christensen BE, Hou-Jensen K, Pedersen NT, Jensen OM, Thorling K, Andersen E, Birgens HS, Drivsholm A, Ellegaard J, Larsen JK, Plesner T, Brown P, Andersen PK, Hansen MM (1997) In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients. Leuk Res 21:1011–1023

    Article  PubMed  CAS  Google Scholar 

  6. Shaffer LG, Tommerup N (eds) (2005) An international system for human cytogenetic nomenclature. Karger S, Basel

  7. Izutsu T, Kudo T, Miura F, Nishiya I (1995) Numerical and structural chromosome abnormalities in an ovarian fibrothecoma. Cancer Genet Cytogenet 83:84–86

    Article  PubMed  CAS  Google Scholar 

  8. Jenkins RB, Bartelt D Jr., Stalboerger P, Persons D, Dahl RJ, Podratz K, Keeney G, Hartmann L (1993) Cytogenetic studies of epithelial ovarian carcinoma. Cancer Genet Cytogenet 71:76–86

    Article  PubMed  CAS  Google Scholar 

  9. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821

    Article  PubMed  CAS  Google Scholar 

  10. Knuutila S, Nylund SJ, Wessman M, Larramendy ML (1994) Analysis of genotype and phenotype on the same interphase or mitotic cell. A manual of MAC (morphology antibody chromosomes) methodology. Cancer Genet Cytogenet 72:1–15

    Article  PubMed  CAS  Google Scholar 

  11. Kristensen GB, Kildal W, Abeler VM, Kaern J, Vergote I, Trope CG, Danielsen HE (2003) Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer. Ann Oncol 14:1494–1500

    Article  PubMed  CAS  Google Scholar 

  12. Kurman RJ (ed) (2002) Blaustein’s pathology of the female genital tract. Springer-Verlag, New York

  13. Leung WY, Schwartz PE, Ng HT, Yang-Feng TL (1990) Trisomy 12 in benign fibroma and granulosa cell tumor of the ovary. Gynecol Oncol 38:28–31

    Article  PubMed  CAS  Google Scholar 

  14. Liang SB, Sonobe H, Taguchi T, Takeuchi T, Furihata M, Yuri K, Ohtsuki Y (2001) Tetrasomy 12 in ovarian tumors of thecoma–fibroma group: a fluorescence in situ hybridization analysis using paraffin sections. Pathol Int 51:37–42

    Article  PubMed  CAS  Google Scholar 

  15. Liehr T, Grehl H, Rautenstrauss B (1995) FISH analysis of interphase nuclei extracted from paraffin-embedded tissue. Trends Genet 11:377–378

    Article  PubMed  CAS  Google Scholar 

  16. Mandahl N (2001) Methods in solid tumors cytogenetics. In: Rooney DE (ed) Human cytogenetics—malignancy and acquired abnormalities. Oxford University Press, Oxford, pp 165–203

    Google Scholar 

  17. Micci F, Teixeira MR, Haugom L, Kristensen G, Abeler VM, Heim S (2004) Genomic aberrations in carcinomas of the uterine corpus. Genes Chromosomes Cancer 40:229–246

    Article  PubMed  CAS  Google Scholar 

  18. Mitelman, F., Johansson, B., Mertens, F. (2006) Mitelman database of chromosome aberrations in cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman

  19. Mrozek K, Limon J, Debniak J, Emerich J (1992) Trisomy 12 and 4 in a thecoma of the ovary. Gynecol Oncol 45:66–68

    Article  PubMed  CAS  Google Scholar 

  20. Nilbert M, Heim S, Mandahl N, Floderus UM, Willen H, Mitelman F (1990) Characteristic chromosome abnormalities, including rearrangements of 6p, del(7q), +12, and t(12;14), in 44 uterine leiomyomas. Hum Genet 85:605–611

    Article  PubMed  CAS  Google Scholar 

  21. Nilbert M, Heim S, Mandahl N, Floderus UM, Willen H, Mitelman F (1990) Trisomy 12 in uterine leiomyomas. A new cytogenetic subgroup. Cancer Genet Cytogenet 45:63–66

    Article  PubMed  CAS  Google Scholar 

  22. Pejovic T (1995) Genetic changes in ovarian cancer. Ann Med 27:73–78

    Article  PubMed  CAS  Google Scholar 

  23. Pejovic T, Heim S, Mandahl N, Elmfors B, Floderus UM, Furgyik S, Helm G, Willen H, Mitelman F (1990) Trisomy 12 is a consistent chromosomal aberration in benign ovarian tumors. Genes Chromosomes Cancer 2:48–52

    Article  PubMed  CAS  Google Scholar 

  24. Persons DL, Hartmann LC, Herath JF, Borell TJ, Cliby WA, Keeney GL, Jenkins RB (1993) Interphase molecular cytogenetic analysis of epithelial ovarian carcinomas. Am J Pathol 142:733–741

    PubMed  CAS  Google Scholar 

  25. Persons DL, Hartmann LC, Herath JF, Keeney GL, Jenkins RB (1994) Fluorescence in situ hybridization analysis of trisomy 12 in ovarian tumors. Am J Clin Pathol 102:775–779

    PubMed  CAS  Google Scholar 

  26. Shashi V, Golden WL, Kap-Herr C, Andersen WA, Gaffey MJ (1994) Interphase fluorescence in situ hybridization for trisomy 12 on archival ovarian sex cord-stromal tumors. Gynecol Oncol 55:349–354

    Article  PubMed  CAS  Google Scholar 

  27. Smith LM, Hu P, Meyer LJ, Coffin CM (2002) Complex karyotypic abnormality in ovarian fibroma associated with Gorlin syndrome. Am J Med Genet 112:61–64

    Article  PubMed  Google Scholar 

  28. Taruscio D, Carcangiu ML, Ward DC (1993) Detection of trisomy 12 on ovarian sex cord stromal tumors by fluorescence in situ hybridization. Diagn Mol Pathol 2:94–98

    PubMed  CAS  Google Scholar 

  29. Tavassoli FA, Devilee P (eds) (2003) World health organization classification of tumors: pathology and genetics of tumors of the breast and female genital organs. IARC, Lyon

  30. Thompson FH, Liu Y, Emerson J, Weinstein R, Makar R, Trent JM, Taetle R, Alberts DS (1994) Simple numeric abnormalities as primary karyotype changes in ovarian carcinoma. Genes Chromosomes Cancer 10:262–266

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesca Micci.

Additional information

Addendum

After submission of this manuscript, an article by Streblow et al. describing a similar study of thecoma–thecofibroma–fibroma tumors was published in Cancer Genetics and Cytogenetics (178:135–140). That study too found that imbalances of other chromosomes than chromosome 12 may represent nonrandom genomic changes in this group of tumors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Micci, F., Haugom, L., Abeler, V.M. et al. Consistent numerical chromosome aberrations in thecofibromas of the ovary. Virchows Arch 452, 269–276 (2008). https://doi.org/10.1007/s00428-007-0561-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-007-0561-x

Keywords

Navigation