Validation of Immunohistochemistry for Identification of IDH1 Mutation in Gliomas
Cecilia M Egoavil, Artemio Paya, Esperanza Irles, Araceli Garcia-Martinez, Jose Luis Soto, Adela Castillejo, Maria Isabel Castillejo, Teresa Quintanar, Joaquin Herrero, Alvaro Rodriguez-Lescure, Maria Jose Portugues, Pedro Moreno, Laura Heredia, Encarnacion Andrada, Ignacio Aranda, Victor M Barbera, Cristina Alenda. University Hospital (HGUA), Alicante, Spain; University Hospital (HGUE), Elche, Alicante, Spain; (HGUE), Elche, Alicante, Spain; (HGUA), Alicante, Spain
Background: Isocitrate Dehydrogenase 1 (IDH1) mutations occur in 60-90% of diffuse astrocytoma and secondary glioblastomas. IDH1 mutation is a relevant marker for diagnosis and prognosis of primary brain tumors. Immunohistochemical (IHC) assessment of this mutation might be a useful and accessible tool to distinguish between neoplastic and gliosis lesions. The aim of this study was the validation of an IHC process in formalin-fixed, paraffin-embedded brain tumor tissue to determine IDH1 mutational status.
Design: A tissue microarray (TMA) built with 171 resected surgical gliomas specimens from Biobank HGUA and HGUE (14 stage I astroytoma; 22 stage II; 20 stage III and 114 glioblatomas) was analyzed by IHC with the mouse monoclonal Anti-Human IDH 1 (R132H Clone H09, Histonova). The TMA was examined by two pathologists. IHC was scored as negative (no staining), positive (cytoplasmic and nuclei staining in >10% of tumor cells) and not evaluable cases. DNA sequencing was used as the gold standard technique to establish the IDH1 mutational status.
Results: Results were available on 155 and 126 cases for IHC and DNA sequencing, respectively. Overall inter-observer agreement was high (weighted κ=0.94, SE: 0.043 CI 0.91-1), with 98.7% concordance (94.9-99.8%). All concordant negative cases were IDH1 wild type (n=105), and all concordant positive cases were IDH1 mutated (n=21) [Sensibility: 100%; specificity: 100%; p=0; statistical power: >95%].
Conclusions: Our study shows that evaluation of IDH1 by immunohistochemistry is highly reproducible with the application of standard immunohistochemical techniques and simple scoring criteria.
Category: Quality Assurance
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 300, Tuesday Morning