Title: Immunohistochemical study of b catenin expression in medulloblastoma and its clinicopathological correlation
Authors: Bhawna Bansal , Karuna Gupta, Swati Aggarwal, Jayanti Mehta, Ajay Yadav
DOI: https://dx.doi.org/10.18535/jmscr/v7i3.77
Abstract
Introduction: Medulloblastoma is the most common of embryonal tumors and most malignant CNS tumor arising in childhood. 4 core molecular subtypes of medulloblastoma are defined named as WNT (Wingless pathway), SHH (Sonic Hedgehog), Group 3 and Group 4.WNT subgroup is best documented and distinguished by nuclear β catenin immunostaining, Catenin β 1 mutations, chromosome 6 loss, alongside its associated favorable prognosis.
Materials and Methods: A laboratory based descriptive type of observational study was carried out in our institute during the year 2017-2018. Total 60 specimens of medulloblastoma were taken. Details about clinical history, histopathological examination and immunohistochemistry were taken and analyzed.
Results: Medulloblastoma studied showed male predominance with highest prevalence in 1-10 years age group. Classic subtype was most common and most common site was midline. β catenin immmunoexpression was studied in all specimens, it was cytoplasmic positive in 40 cases and negative in 20 cases. Its expression is correlated with various epidemiological variables like age, sex, desmoplasia, apoptosis, anaplasia, necrosis etc., however no significant statistically difference was seen in relation to these variables.
Conclusion: Studies aimed at correlating treatment protocols and outcome with these histological and molecular subtypes are warranted to optimize treatment protocols and for prognostication. While we utilized antibody β-catenin to identify the WNT subtype of medulloblastomas, a larger panel of antibodies like GAB-1, YAP-1 and β Catenin are required to better characterize this heterogeneous group of tumors.
Keywords: Medulloblastoma, b Catenin, Immunohistochemistry.
References
- Giangaspero F, Eberhart CG, Haapasalo H et al. medulloblastoma. In : Louis D N, Ohgaki H, Weistler O D et al. (eds) WHO classification of tumours of the central nervous system. IAR Press, Lyon, France;2007. p 132-140.
- Silva R, Marie SK, Uno M et al. Ctnnb1, Axin1 and Apc expression analysis of different medulloblastoma variants. Clinics (Sao Paulo) 2013;68:167–172.
- Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012; 23(4):465-72.
- He TC, Sparks AB, Rago C, et al. Identification of c-MYC as a target of the APC pathway. Science 1998;281:1509–12.
- Schwalbe EC, Lindsey JC, Straughton D, Hogg TL, Cole M, Megahed H, et al. Rapid diagnosis of medulloblastoma molecular subgroups. Clin Cancer Res.2011; 17:1883–1894
- Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol Off J Am SocClin Oncol. 2011 Apr 10;29(11):1408–14.
- Kenney AM, Rowitch DH. Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Molecular and cellular biology. 2000;20:9055–67.
- Fattet S, Haberler C, Legoix P, et al. Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. The Journal of pathology. 2009;218:86–94
- RM Samaka, MMA El-Wahed, MA Kandil, E Abdelzaher, MI Shaaban, RA Allah. Immunohistochemical localization of b-catenin in medulloblastoma. Menoufia Med J 2014; 27 :10-15.
- Yokota N, Nishizawa S, Ohta S, Date H, Sugimura H, et al. Role of Wnt pathway in medulloblastoma oncogenesis. Int J Cancer .2002;101: 198–201.
- Korshunov A, Remke M, Werft W, Benner A, Ryzhova M, Witt H, et al. Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification. J Clin Oncol .2010;28:3054–3060
- Kaur K, Kakkar A, Kumar A, Purkait S, Mallick S, Suri V, et al. Clinicopathological characteristics, molecular subgrouping, and expression of miR-379/miR-656 cluster (C14MC) in adult medulloblastomas. J NeuroOncol 2016. Dec;130(3):423-430.
- Pizem J, Cör A, ZadravecZaletel L, Popovic M. Prognostic significance of apoptosis in medulloblastoma. Neurosci Lett. 2005 Jun 10-17;381(1-2):69-73.
- Giangaspero F, Wellek S, Masuoka J, Gessi M, Kleihues P, Ohgaki H. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol (2006) 112(1):5–1210.
- Taomoto K, Tomita T, Raimondi AJ, Leestma JE. Medulloblastoma in childhood: histological factors influencing the patients’ outcome. Child's Nervous System. 1987; 3:354–360.
- Eberhart CG, Kepner JL, Goldthwaite PT, et al. Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer 2002; 94: 552–60.
- Utsuki S, Oka H, Sato Y, Tsutiya B, Kondo K, Tanizaki Y, et al. N-cadherins and beta-catenin expression in medulloblastoma and atypical teratoid/rhabdoid tumor Neurol Med Chir.2004; 44: 402–406