Pathology & Oncology Research

, 17:697 | Cite as

Expression and Amplification of Topoisomerase-2α in Type 1 and Type 2 Papillary Renal Cell Carcinomas and Its Correlation with HER2/neu Amplification

  • Fusun Duzcan
  • Suleyman Ender Duzcan
  • Sait Sen
  • Kutsal Yorukoglu
  • Vildan Caner
  • Nilay Sen Turk
  • Gokhan Ozan Cetin
  • Canan Kelten
  • Burcin Tuna
  • Banu Sarsik
  • Emre Tepeli
Research
First Online:
Received:
Accepted:

Abstract

The current study was undertaken to investigate chromosomal and genetical aberrations leading to overexpression of Topoisomerase-2α (TOP2α) and to reveal the possible association of these aberrations with HER2/neu overexpression and gene amplification, and to search for the relationship between TOP2α and HER2/neu status with prognostical biomarkers in papillary renal cell carcinoma (RCC), a group of tumors with diverse molecular, chromosomal and clinical features. Archival cases of papillary RCC obtained from Departments of Pathology of Pamukkale, Ege and Dokuz Eylul Universities were studied in two groups (type 1 and type 2) each containing 20 cases. The level of TOP2α and HER2/neu expression by tumor cells were determined immunohistochemically. A multicolor FISH probe was used to define both amplification of HER2/neu and TOP2α genes, and polysomy 17. The ratio of cells expressing TOP2α in type 1 and type 2 papillary RCC were 24.29% and 6.89%, respectively. The difference was statistically significant comparing the average or median values of groups separately (p = 0.002). The expression levels of TOP2α and HER2/neu were also correlated. TOP2α and HER2/neu were co-amplified in both groups. Immunohistochemical expression was not observed in 15 of 23 cases with HER2/neu amplification. The most frequent finding detected by FISH method was polysomy of chromosome 17. We had contradictory results compared with the findings reported in the limited numbers of literature. It shows us that papillary RCC constitute a heterogenous group of tumors with various cytogenetic features and morphological classification of these tumors may not be compatible with their molecular characteristics.

Keywords

Papillary renal cell carcinoma Topoisomerase-2α HER2/neu FISH Immunohistochemistry 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

The authors wish to acknowledge the financial support provided by a grant from The Scientific and Technological Research Council of Turkey, TUBITAK (Grant No. 108S298).

References

  1. 1.
    Eble J, Sauter G, Epstein J, Sesterhenn I (2004) Tumours of the urinary system and male genital organs. In: Eble J, Sauter G, Epstein J, Sesterhenn I (eds) World health organization classification of tumours. IARC, Lyon, pp 27–29Google Scholar
  2. 2.
    Delahunt B, Eble JN (1997) Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 10(6):537–544PubMedGoogle Scholar
  3. 3.
    Murphy WM, Grignon DJ, Perlman EJ (2004) Tumors of the kidney, bladder and related urinary structures. AFIP atlas of tumor pathology, 4th series. American Registry of Pathology, Washington, pp 123–130Google Scholar
  4. 4.
    Petersen RO, Sesterhenn IA, Davis CJ (2009) Urologic pathology, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, pp 54–56Google Scholar
  5. 5.
    Delahunt B, Eble J, McCredis M, Bethwaite P, Stewart J, Bilous M (2001) Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases. Hum Pathol 32:590–595PubMedCrossRefGoogle Scholar
  6. 6.
    Pignot G, Elie C, Conquy S et al (2007) Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. Urology 69:230–235PubMedCrossRefGoogle Scholar
  7. 7.
    Jiang F, Richter J, Schraml P, Bubendorf L, Gasser T, Sauter G, Mihatsch MJ, Moch H (1998) Chromosomal imbalances in papillary renal cell carcinoma. Am J Pathol 153:1467–1473PubMedCrossRefGoogle Scholar
  8. 8.
    Sanders ME, Mick R, Tomaszewski JE, Barr FG (2002) Unique patterns of allelic imbalance distinguish type 1 from type 2 sporadic papillary renal cell carcinoma. Am J Pathol 161:997–1005PubMedCrossRefGoogle Scholar
  9. 9.
    Kovacs G, Fuzesi L, Emanual A, Kung HF (1991) Cytogenetics of papillary renal cell tumors. Genes Chromosom Cancer 3:249–255PubMedCrossRefGoogle Scholar
  10. 10.
    Glukhova L, Goguel AF, Chudoba I, Angevin E, Pavon C, Terrier-Lacombe MJ, Meddeb M, Escudier B, Bernheim A (1998) Overpresentation of 7q31 and 17q in renal cell carcinomas. Genes Chromosom Cancer 22:171–178PubMedCrossRefGoogle Scholar
  11. 11.
    Hughson MD, Dickman K, Bigler SA, Meloni AM, Sandberg AA (1998) Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization. Cancer Genet Cytogenet 106:93–104PubMedCrossRefGoogle Scholar
  12. 12.
    Hughson MD, Bigler S, Dickman K, Kovacs G (1999) Renal cell carcinoma of end-stage renal disease: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification. Mod Pathol 12:301–309PubMedGoogle Scholar
  13. 13.
    Dekel Y, Frede T, Kugel V, Neumann G, Rassweiler J, Koren R (2005) Human DNA topoisomerase II-alpha expression in laporospically treated renal cell carcinoma. Oncol Rep 14:271–274PubMedGoogle Scholar
  14. 14.
    Cooper GM, Hausman RE (2006) Genomik DNA’nın replikasyonu, korunması ve yeniden düzenlenmesi. In: Sakızlı M, Atabey N (eds) Hücre-Moleküler Yaklaşım. Translational, 3rd edn. İzmir Tıp Kitapevi, İzmir, pp 186–187Google Scholar
  15. 15.
    Jarvinen TAH, Liu ET (2003) Topoisomerase IIα gene (TOP2A) amplification and deletion in cancer—more common than anticipated. Cytopathology 14:309–313PubMedCrossRefGoogle Scholar
  16. 16.
    Varis A, Wolf M, Monni O, Vakkari ML, Kokkola A, Moskalk C, Frierson H Jr, Powell SM, Knuutila S, Kalioniemi A, El-Rifai W (2002) Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res 62:2625–2629PubMedGoogle Scholar
  17. 17.
    Wikman H, Kettunen E, Seppänen JK, Karjalainen A, Hollmén J, Anttila S, Knuutila S (2002) Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 21:5804–5813PubMedCrossRefGoogle Scholar
  18. 18.
    Yang XJ, Tan MH, Kim HL et al (2005) A molecular classification of papillary renal cell carcinoma. Cancer Res 65:5628–5637PubMedCrossRefGoogle Scholar
  19. 19.
    Vang Nielsen K, Muller S, Møller S, Schønau A, Balslev E, Knoop AS, Ejlertsen B (2010) Aberrations of ERBB2 and TOP2A genes in breast cancer. Mol Oncol 4:161–168CrossRefGoogle Scholar
  20. 20.
    Reese DM, Small EJ, Magrane G, Waldman FM, Chew K, Sudilovsky D (2001) HER2 protein expression and gene amplification in androgen-independent prostate cancer. Am J Clin Pathol 116:234–239PubMedCrossRefGoogle Scholar
  21. 21.
    Press MF, Finn RS, Cameron D, Di Leo A, Geyer CE, Villalobos IE, Santiago A, Guzman R, Gasparyan A, Ma Y, Danenberg K, Martin AM, Williams L, Oliva C, Stein S, Gagnon R, Arbushites M, Koehler MT (2008) HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res 14:7861–7870PubMedCrossRefGoogle Scholar
  22. 22.
    Caner V, Turk NS, Duzcan F, Tufan NL, Kelten EC, Zencir S, Dodurga Y, Bagci H, Duzcan SE (2008) No strong association between HER-2/neu protein overexpression and gene amplification in high-grade invasive urothelial carcinomas. Pathol Oncol Res 14:261–266PubMedCrossRefGoogle Scholar
  23. 23.
    Järvinen TA, Tanner M, Bärlund M, Borg A, Isola J (1999) Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer. Genes Chromosom Cancer 26:142–150PubMedCrossRefGoogle Scholar
  24. 24.
    Järvinen TA, Tanner M, Rantanen V, Bärlund M, Borg A, Grénman S, Isola J (2000) Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol 156:839–847PubMedCrossRefGoogle Scholar
  25. 25.
    Di Leo A, Isola J (2003) Topoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning? Clin Breast Cancer 4:179–186PubMedCrossRefGoogle Scholar
  26. 26.
    Bhargava R, Lal P, Chen B (2005) HER-2/neu and topoisomerase IIa gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol 123:889–895PubMedCrossRefGoogle Scholar
  27. 27.
    Wang Q, Zambetti GP, Suttle DP (1997) Inhibition of DNA topoisomerase II alpha gene expression by the p53 tumor suppressor. Mol Cell Biol 17:389–397PubMedGoogle Scholar
  28. 28.
    Wu Z, Reed RF, Parker Suttle D (2003) Nuclear factor-y binding to the topoisomerase IIα promoter is inhibited by both the p53 tumor suppressor and anticancer drugs. Mol Pharmacol 63:359–367PubMedCrossRefGoogle Scholar
  29. 29.
    Baylin SB, Jones PA (2007) Epigenetic determinants of cancer. In: Allis CD, Jenuwein T, Reinberg D (eds) Epigenetics. Cold Spring Harbor, pp 457–476Google Scholar
  30. 30.
    Barrandon C, Spiluttini B, Bensaude O (2008) Non-coding RNAs regulating the transcriptional machinery. Biol Cell 100:83–95PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2011

Authors and Affiliations

  • Fusun Duzcan
    • 1
  • Suleyman Ender Duzcan
    • 2
  • Sait Sen
    • 3
  • Kutsal Yorukoglu
    • 4
  • Vildan Caner
    • 5
  • Nilay Sen Turk
    • 2
  • Gokhan Ozan Cetin
    • 1
  • Canan Kelten
    • 2
  • Burcin Tuna
    • 4
  • Banu Sarsik
    • 3
  • Emre Tepeli
    • 1
  1. 1.Department of Medical Genetics, Medical FacultyPamukkale UniversityDenizliTurkey
  2. 2.Department of Pathology, Medical FacultyPamukkale UniversityDenizliTurkey
  3. 3.Department of Pathology, Medical FacultyEge UniversityIzmirTurkey
  4. 4.Department of Pathology, Medical FacultyDokuz Eylül UniversityIzmirTurkey
  5. 5.Department of Medical Biology, Medical FacultyPamukkale UniversityDenizliTurkey

Personalised recommendations