Immunohistochemical expression of IDH1R132H in Astrocytic tumours and its association with histopathological grade, TP53 and EGFR protein expression
Keywords:
IDH, glioma, EGFR, TP53, immunohistochemistry, genotypeAbstract
Background: Molecular studies have uncovered that histopathologically diagnosed Astrocytomas are genetically heterogeneous. Majority of Diffuse Astrocytomas (DA), Anaplastic Astrocytomas (AA) and secondary Glioblastoma multiforme (GBM) have concurrent mutations of IDH, TP53 and ATRX. Astrocytomas without IDH mutation have distinct genotype and poor prognosis. Primary GBM show EGFR amplification and lack IDH mutation.
Methods: We studied 95 Astrocytic tumors including 15 Pilocytic Astrocytoma (PA), 21 Diffuse astrocytomas, 7 Anaplastic astrocytomas and 52 GBM using tissue-microarray (TMA) to assess immunohistochemical expression of IDH1R132H, TP53 and EGFR protein in all four grades and the association between these three immunohistochemical markers. TMA blocks with core size 3.0 mm were constructed using manual tissue-microarrayer. IHC for IDH1R132H, TP53 and EGFR was performed.
Results: 13%(2/15) of PA showed IDH1R132H expression. TP53 and EGFR expression was not seen in any case. 52%(11/21), 71%(15/21) and 9%(2/21) of DA showed expression of IDH1, TP53 and EGFR respectively. Frequency of mutant IDH1, TP53 and EGFR in Anaplastic astrocytoma was 85%(6/7), 85%(6/7) and 0%(0/7). Among GBMs there was significant difference in IHC expression of IDH1 and EGFR. Primary GBMs show high EGFR expression of 70%(26/37) and low IDH1 expression of 21%(8/37). Secondary GBM in contrast show higher IDH1 expression 80%(12/15) and low EGFR expression of 13%(2/15).
Conclusion:Â IDH and TP53 mutations are seen in majority of DA, AA and secondary GBM and are hallmarks of these tumors. Primary GBMs have distinct molecular pathway. They lack IDH, TP53 mutation and overexpress EGFR.
DOI:10.21276/APALM.1458
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