WT1 protein expression in astrocytic tumors and its relationship with cellular proliferation index

Authors

Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Although Wilms' tumor gene (WT1) was initially known as a tumor marker in Wilms' tumor, nowadays its role is well known in other sorts of malignancy. This study aimed to evaluate WT1 protein expression levels and its association with cellular proliferation in astrocytic brain tumors by immunohistochemical methods.
Materials and Methods: This cross-sectional study performed on 73 randomly selected archived tissue samples of astrocytic brain tumors. Sections were observed after immunohistochemical staining regarding WT1 protein expression and MIB-1 staining index. Tumors were classified based on World Health Organization grading system.
Results: WT1 protein expression was seen in the majority of samples (97.3%) with significantly higher index in high-grade tumors (P<0.001). MIB-1 staining index was also significantly higher in high-grade tumors (P<0.001). Moreover, a significantly positive correlation was found between WT1 protein expression and MIB-1 staining index (r: 0.64, P<0.001).
Conclusion: Astrocytic brain tumors express WT1 protein. It was also found that high-grade tumors are accompanied with higher WT1 protein expression, which is correlated with MIB-1 staining index. WT1 can be used as a marker of malignant cell proliferation and diagnostic tool to differentiate normal astrocytes from neoplastic cells.

Keywords

1. Hashiba T, Izumoto S, Kagawa N, Suzuki T, Hashimoto N, Maruno M, et al. Expression of WT1 protein and correlation with cellular proliferation in glial tumors. Neurol Med Chir (Tokyo) 2007;47:165-70; discussion 70.  Back to cited text no. 1
    
2. Cilloni D, Gottardi E, De Micheli D, Serra A, Volpe G, Messa F, et al. Quantitative assessment of WT1expression by real time quantitative PCR may be a useful tool for monitoring minimal residual disease in acute leukemia patients. Leukemia 2002;16:2115-21.  Back to cited text no. 2
    
3. Oji Y, Suzuki T, Nakano Y, Maruno M, Nakatsuka S, Jomgeow T, et al. Overexpression of the Wilms' tumor gene W T1 in primary astrocytic tumors. Cancer Sci 2004;95:822-7.  Back to cited text no. 3
    
4. Gessler MP, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletions in Wilms' tumours of a zinc-finger gene identified by chromosome jumping. Nature 1990;343:774-8.  Back to cited text no. 4
    
5. Inoue K, Sugiyama H, Ogawa H, Nakagawa M, Yamagami T, Miwa H, et al. WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood 1994;84:3071-9.  Back to cited text no. 5
    
6. Oji Y, Miyoshi S, Maeda H, Hayashi S, Tamaki H, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers. Int J Cancer Res Clin Oncol 2002;100:297-303.  Back to cited text no. 6
    
7. Oji Y, Yamamoto H, Nomura M, Nakano Y, Ikeba A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma. Cancer Sci 2003;94:712-7.  Back to cited text no. 7
    
8. Loeb DM, Evron E, Patel CB, Sharma PM, Niranjan B, Buluwela L, et al. Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer Res 2001;61:921-5.  Back to cited text no. 8
    
9. Miyoshi Y, Ando A, Egawa C, Taguchi T, Tamaki Y, Tamaki H, et al. High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients. Clin Cancer Res 2002;8:1167-71.  Back to cited text no. 9
    
10. Oji Y, Miyoshi Y, Koga S, Nakano Y, Ando A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in primary thyroid cancer. Cancer Sci 2003;94:606-11.  Back to cited text no. 10
    
11. Menssen HD, Bertelmann E, Bartelt S, Schmidt RA, Pecher G, Schramm K, et al. Wilms' tumor gene (WT1) expression in lung cancer, colon cancer and glioblastoma cell lines compared to freshly isolated tumor specimens. J Cancer Res Clin Oncol 2000;126:226-32.  Back to cited text no. 11
    
12. Nakahara Y, Okamoto H, Mineta T, Tabuchi K. Expression of theWilms' tumor gene productWT1 in glioblastomas and medulloblastomas. Brain Tumor Pathol 2004;21:113-6.  Back to cited text no. 12
    
13. Clark AJ, Dos Santos WG, McCready J, Chen MY, Van Meter TE, Ware JL, et al. Wilms tumor1 expression in malignant gliomas and correlation of ?KTS isoforms with p53 status. J Neurosurg 2007;107:586-92.  Back to cited text no. 13
    
14. Izumoto S, Tsuboi A, Oka Y, Suzuki T, Hashiba T, Kagawa N, et al. Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme. J Neurosurg 2008;108:963-71.  Back to cited text no. 14
    
15. Morita S, Oka Y, Tsuboi A, Kawakami M, Maruno M, Izumoto S, et al. A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: Safety assessment based on the phase I data. Jpn J Clin Oncol 2006;36:231-6.  Back to cited text no. 15
    
16. Oka Y, Udaka K, Tsuboi A, Elisseeva OA, Ogawa H, Aozasa K. Cancer immunotherapy targeting Wilms' tumor gene WT1 product. J Immunol 2000;164:1873-80.  Back to cited text no. 16
    
17. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Halber DA, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 1990;60:509-20.  Back to cited text no. 17
    
18. Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature 1990;346:194-7.  Back to cited text no. 18
    
19. Armstrong JF, Pritchard-Jones K, Bickmore WA. The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. Mech Dev 1993;40:85-97.  Back to cited text no. 19
    
20. Johannessen A, Torp SH. The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 2006;12:143-7.  Back to cited text no. 20
    
21. Prayson RA. The utility of MIB-1/Ki-67 imunostaining in the evaluation of central nervous system neoplasms. Adv Anat Pathol 2005;12:144-8.  Back to cited text no. 21
    
22. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97-109.  Back to cited text no. 22
    
23. Schittenhelm J, Beschorner R, Simon P, Tabatabai G, Herrmann C, Schlaszus H, et al. Diagnostic value of WT1 in neuroepithelial tumours. Neuropathol Appl Neurobiol 2009;35:69-81.  Back to cited text no. 23
    
24. Schittenhelm J, Mittelbronn M, Nguyen TD, Meyermann R, Beschorner R. WT1 expression distinguishes astrocytic tumor cells from normal and reactive astrocytes. Brain Pathol 2008;18:344-53.  Back to cited text no. 24
    
25. Bourne TD, Elias WJ, Lopes MB, Mandell JW. WT1 is not a reliable marker to distinguish reactive from neoplastic astrocyte populations in the central nervous system. Brain Pathol 2010;20:1090-5.  Back to cited text no. 25
    
26. Giannini C, Scheithauer BW, Burger PC, Christensen MR, Wollan PC, Sebo TJ, et al. Cellular proliferation in pilocytic and diffuse astrocytomas. J Neuropathol Exp Neurol 1999;58:46-53.  Back to cited text no. 26
    
27. Kamiya M, Nakazato Y. The expression of cell cycle regulatory proteins in oligodendroglial tumors. Clin Neuropathol 2002;21:52-65.  Back to cited text no. 27
    
28. Machen SK, Prayson RA. Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: A study of 48 cases. Hum Pathol 1998;29:1511-6.  Back to cited text no. 28