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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(06): 569-576
DOI: 10.1055/s-0041-1741061
Original Article

Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute

Ramya Lakshmi Veduruvada
1   Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Megha S. Uppin
1   Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Meher Lakshmi Konatam
2   Department of Medical Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Rajesh Alugolu 
3   Department of Neurosurgery, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Vamsi Krishna Yeramneni
3   Department of Neurosurgery, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Suchanda Bhattacharjee 
3   Department of Neurosurgery, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Mudumba Vijaya Saradhi
3   Department of Neurosurgery, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Monica Malik Irukulla
4   Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
,
Madhumohan Rao
5   Stem Cell Facility and Regenerative Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
,
Nagaraj Velugonda 
6   Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
› Author Affiliations Source of Funding Nil.
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Abstract

Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines.

Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up.

Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test.

Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively.

Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.

Keywords

glioma - diffuse astrocytoma - immunohistochemistry - IDH1/2 mutations - Sanger sequencing - survival


Publication History

Article published online:
31 December 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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