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DNA topoisomerase IIα protein and mRNA expression in intracranial meningiomas

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Abstract

We examined the expression of DNA topoisomerase IIα (Topo IIα) immunohistochemically using a monoclonal antibody and compared its proliferative potential [MIB-1 labeling index (LI)] and recurrence to verify the possible influence of Topo IIα on the progress of meningiomas. The reverse transcription-polymerase chain reaction (RT-PCR) assay was also performed to evaluate the expression of Topo IIα mRNA. Formalin-fixed, paraffin-embedded tissue sections of 52 meningiomas (18 meningothelial types, 16 fibrous types, 4 transitional types, 4 psammomatous types, 1 angiomatous type, 1 secretory type, 5 atypical types, and 3 anaplastic types) were used for immunostaining. The Topo IIα labeling index (LI) was 1.4±1.9% (mean ± SE) in benign meningiomas and 4.5±1.6% in atypical or anaplastic meningiomas, representing significant differences between them (P<0.0001). RT-PCR assay revealed that Topo IIα mRNA expression was associated with Topo IIα LI. A significant correlation was seen between Topo IIα LI and MIB-1 LI (r=0.517;P<0.01). Recurrence was significantly more frequent in patients with more than 1.5% of Topo IIα LI than in those with 1.5% or less (P<0.005). In conclusion, Topo IIα protein and mRNA expression correlated with clinical malignancy and the potential for predicting the regrowth of meningiomas.

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References

  1. Adegbite AB, Khan MI, Paine KW, et al (1983) The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51–56

    PubMed  CAS  Google Scholar 

  2. Jaaskelainen J (1986) Seemingly complete removal of histologically benign intracranial meningioma: late recurrence rate and factors predicting recurrence in 657 patients. A multivariate analysis. Surg Neurol 26:461–469

    Article  PubMed  CAS  Google Scholar 

  3. Mirimanoff RO, Dosoretz DE, Linggood RM, et al (1985) Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:18–24

    Article  PubMed  CAS  Google Scholar 

  4. Kleihues P, Burger PC, Scheithauer BW (1993) Histological typing of tumours of the central nervous system. 2nd ed. Springer-Verlag, Berlin, pp 11–30

    Google Scholar 

  5. McKeever PE, Ross DA, Strawderman MS, et al (1997) A comparison of the predictive power for survival in gliomas provided by MIB-1, bromodeoxyuridine and proliferating cell nuclear antigen with histopathologic clinical parameters. J Neuropathol Exp Neurol 56:798–805

    Article  PubMed  CAS  Google Scholar 

  6. Onda K, Davis RL, Shibuya M, et al (1994) Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67 proliferating cell indices in cerebral gliomas. Cancer 74:1921–1926

    Article  PubMed  CAS  Google Scholar 

  7. Hoshi M, Yoshida K, Shuimazaki K, et al (1997) Correlation between MIB-1 staining indices and recurrence in low grade astrocytomas. Brain Tumor Pathol 14:47–51

    Article  PubMed  CAS  Google Scholar 

  8. Hsu DW, Louis DN, Efird JT, et al (1997) Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas. J Neuropathol Exp Neurol 56:857–865

    PubMed  CAS  Google Scholar 

  9. Nakaguchi H, Fujimaki T, Matsuno A, et al (1999) Postoperative residual tumor growth of meningioma can be predicted by MIB-1 immunohistochemistry. Cancer 85:2249–2254

    Article  PubMed  CAS  Google Scholar 

  10. Pommier Y, Bertrand R (1993) The mechanisms of formation of chromosomal aberrations: role of eukaryotic DNA topoisomerases. In: Kirsch IR (ed) The causes and consequences of chromosomal aberrations. Boca Raton, FL, USA: CRC Press pp 277–309

    Google Scholar 

  11. Cummings J, Smyth JF (1993) DNA topoisomerase I and II as targets for rational design of new anticancer drugs. Ann Oncol 4:533–543

    PubMed  CAS  Google Scholar 

  12. Chung TDY, Drake FH, Tan KB, et al (1989) Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes. Proc Natl Acad Sci USA 86:9431–9435

    Article  PubMed  CAS  Google Scholar 

  13. Tsai-Plugfeder M, Liu LF, Liu AA, et al (1988) Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21–22. Proc Natl Acad Sci USA 85:7177–7181

    Article  Google Scholar 

  14. Tan KB, Dorman TE, Falls KM, et al (1992) Topoisomerase IIα and topoisomerase IIβ genes: characterization and mapping to human chromosome 17 and 3, respectively. Cancer Res 52:231–234

    PubMed  CAS  Google Scholar 

  15. Drake FH, Hofmann GA, Batrus HF, et al (1991) Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry 28:154–160

    Google Scholar 

  16. Woessner RD, Mattern MR, Mirabelli CK, et al (1991) Proliferation- and cell cycle-dependent differences in the expansion of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ 2:209–214

    PubMed  CAS  Google Scholar 

  17. Negri C, Chisa R, Cerino A, et al (1992) Monoclonal antibodies to human DNA topoisomerase I and two isoforms of DNA topoisomerase II: 170- and 180-kDa isozymes. Exp Cell Res 200:452–459

    Article  PubMed  CAS  Google Scholar 

  18. Hellemans P, Van Dam PA, Geyskens M, et al (1995) Immunohistochemical study of topoisomerase IIα expression in primary ductal carcinoma of the breast. J Clin Pathol 48:147–150

    PubMed  CAS  Google Scholar 

  19. Lohri A, Reuter J, Gudat F, et al (1997) Topoisomerase IIα mRNA and tumour cell proliferation in non-Hodgkin's lymphoma. J Clin Pathol 50:22–26

    PubMed  CAS  Google Scholar 

  20. Tandon AK, Hilsenbeck SG, Clark GM, et al (1991) Significance of topoisomerase II in clinical breast cancer. Proc Am Assoc Cancer Res 32:350–352

    Google Scholar 

  21. Taniguchi K, Wakabayashi T, Yoshida T, et al (1999) Immunohistochemical staining of DNA topoisomerase IIα in human gliomas. J Neurosurg 91:477–482

    Article  PubMed  CAS  Google Scholar 

  22. Tuccari G, Rizzo A, Giuffre G, et al (1993) Immunocytochemical detection of topoisomerase type II in primary breast carcinomas: correlation with clinicopathological features. Virchows Archiv A Pathol Anat 423:51–55

    Article  CAS  Google Scholar 

  23. Withoff S, Van Der Zee AGJ, De Jong S, et al (1999) DNA topoisomerase IIα and IIβ expression in human ovarian cancer. Br J Cancer 79:748–753

    Article  PubMed  CAS  Google Scholar 

  24. Burger PC, Shibata T, Kleihues P (1986) The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology. Am J Surg Pathol 10:661–617

    Google Scholar 

  25. Gerdes J, Lemke H, Baisch H, et al (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715

    PubMed  CAS  Google Scholar 

  26. Key G, Becker MHG, Baron B, et al (1993) New Ki-67-equivalent murine monoclonal antibodies (MIB1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive element encoding for the Ki-67 epitope. Lab Invest 68:629–636

    PubMed  CAS  Google Scholar 

  27. Kunishio K, Mishima N, Matsuhisa T, et al (1994) Immunohistochemical demonstration of DNA polymerase α human brain tumor cells. J Neurosurg 72:268–272

    Google Scholar 

  28. Munakata S, Hendricks JB (1993) Effect of fixation time and microwave oven heating time on retrieval of the Ki-67 antigen from paraffin embeded tissue. J Histochem Cytochem 41:1241–1246

    PubMed  CAS  Google Scholar 

  29. Sallinen PK, Haapasalo HK, Visakorpi T, et al (1994) Prognostication of astrocytoma patient survival by Ki-67 (MIB-1), PCNA, and S-phase fraction using archival paraffin-embeded samples. J Pathol 174:275–282

    Article  PubMed  CAS  Google Scholar 

  30. Tanaka M, Kubo O, Tajika Y, et al (1999) Immunohistochemical evaluation of intracranial recurrent meningiomas: correlation of topoisomerase IIα expression and cell proliferative potential. Brain and Nerve 51:1033–1039

    PubMed  CAS  Google Scholar 

  31. Morisaki K, Kuoda S, Matsumto Y, et al (2000) Expression of DNA topoisomerase I, IIα and IIβ in human brain tumors. Brain Tumor Pathol 17:7–13

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Katsuzo Kunishio.

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Kunishio, K., Morisaki, K., Matsumoto, Y. et al. DNA topoisomerase IIα protein and mRNA expression in intracranial meningiomas. Brain Tumor Pathol 17, 105–110 (2000). https://doi.org/10.1007/BF02484281

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