Title: Immunohistochemical Expression of WT1 in Glial Neoplasm and its Significance
Authors: Mathur Kusum, Vijay Ramita
DOI: https://dx.doi.org/10.18535/jmscr/v7i8.127
Abstract
Introduction: WT1 is a transcription factor related to growth and differentiation of cells. WT1 overexpression is observed in majority of primary glial tumours. However, it is differential expression of WT1 in different grades of tumour, that might influence the biological behavior of gliomas and thus prognosis. At present, as WT1 is regarded as a molecular target for immunotherapy for malignant gliomas, an appropriate evaluation of WT1 expression is essential. The present study was planned to assess the WT1 expression in various grades and types of glial neoplasm and correlate this with mean mitosis and tumour grade so as to exclude or include WT1 as a potential prognostic factor in patients with glial tumours.
Materials and Methods: A descriptive observational study was carried out in Department of Pathology, S.M.S. Medical College, Jaipur (Rajasthan). Total 50 cases of glioma were included in the study.These were stained with Hematoxylin and Eosin followed by Immunostaining with WT1. Clinical, histopathological and Immunohistochemical profile of glial tumours were recorded and analysed.
Results: Mean age of study subjects was 35.64±16.03 years (male 38.65±15.06 years and female 30.74±16.74 years). 62% were males and 38% were females. Glioblastoma was the most frequent neoplasm (40%). Highest number of Tumours belonged to Grade-IV (40%) followed by Grade-II (38%), Grade-I (12%) and Grade-III (10%) according to WHO grading system for glial tumours. Highest mean mitotic value was obtained in grade-IV tumours (7.80) while it was 0 in grade-I tumours (p<0.001). Positive staining for WT 1 immunoexpression was observed in 45 cases (90%) ranging from score 2 to score 6. Mean WT1 score for grade-I tumours was 2.50, for grade-II tumours 2.95, for grade-III tumours 2.60 and for grade-IV tumours 5.60 (p<0.001). There was a strong correlation between WHO grade, mitosis and WT1 Score. Also, WT1 showed a direct independent correlation with mitotic activity of tumours.
Conclusion: WT1 immuno-expression bears a direct relation to tumour grade as well as mitotic activity. Thus, it appears to be involved in tumour growth and bears a prognostic significance. This makes it a useful molecular target for immunotherapy.
Keywords: Glial Neoplasm, Histopathology, Immunohistochemical, WT1 immunoexpression.
References
- Dasgupta A, Gandhi T, Jalali R. Indian data on central nervous tumours: A summary of published work. Southa Asian J Cancer. 2016;5(3):147-53.
- Schittenhelm J, Mittelbronn M, Nguyen TD, Meyermann R, Beschorner R. WT1 expression distinguish esastrocytic tumour cells from normal and reactive astrocytes. Brain Pathol 2008;18(3):344-53.
- Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GAP. Homozygous deletion in Wilms tumours of a zinc finger gene identified by chromosome jumping. Nature1990;343:774-8.
- Sharma, PM, M Bowman, SL Madden, FJ Rauscher and S Sukumar. RNA editing in the Wilms’ tumour susceptibility gene, WT1. Genes Dev. 1994;8:720-31.
- Davies R, Moore A, Schedl A, Bratt E, Miyahawa K, Ladomery Metal. Multiple roles for the Wilms’ tumour suppressor, WT1. Cancer Res 1999;59:1747-50
- Sugiyama H. Wilms’ tumour gene WT1: its oncogenic function and clinical application. Int J Hematol2001;73:177-87.
- Sugiyama H. Cancer immunotherapy targeting WT1 protein. Int J Hematol2002;76:127-32.
- S Izumoto, A Tsuboi, Y Oka, T Suzuki, T Hashiba, N kagwa et al. Phase II clinical trial of Wilms’ tumour 1 peptide vaccination for patients with recurrent glioblastoma multiforme. J. Neurosurg 2008;108:963-71.
- N Hashimoto, A Tsuboi, N Kagwa, Y Chiba, SIzumoto, M Kinoshitaetal. Wilms tumour 1 peptide combined with temozolamide against newly diagnosed Glioblastoma: safety and impact on immunological response. Cancer Immunol. Immunother 2015;64:707-16
- Bassam AM, Lubna O, Abdel-Salam and D Khairy. WT1 expression in Glial tumours: Its Possible Role in Angiogenesis and Prognosis. Academic J CancerRes. 2014;7(2):50-58.
- Ibrahim BB, MM Sami Salem, AAM Hareedy, NSAl Hariry. Histopathological study and Immunohistochemical Expression of WT1 Protein in Different Types and Grades of Astrocytic Tumours. Academic J Cancer Res. 2016;9(1):01-06.
- Schittenhelm J, Beschorner R, Simon P, Tabatabai G, Herrmann C, Schlaszus H, Capper D et al. Diagnostic value of WT1 in neuroepithelial tumours. Neuropathol Appl Neurobiol 2009;35(1):69- 81.
- Hashiba T, S Izumoto, N Kagwa, T Suzuki, N Hashimoto, M Maruno, T Yoshimine. Expression of WT1 protein and correlation with cellular proliferation in glial tumours. Neurol Med Chir (Tokyo).2007;47:165-70.
- Oji Y, T Suzuki, Y Nakano, M Maruno, S Nakatsuka, T Jomgeowetal. Over expression of the Wilms' tumour gene WT1 in astrocytic tumours. Cancer Sci. 2004;95:822-7.
- Raucher J, R Beschorner, M Gierke, S Bisdas, C Braun, FH Ebner, J Schittenhelm. WT1 expression increases with malignancy and indicates unfavourable outcome in astrocytoma. J. Clin Pathol 2014;67(7):556-61.