Alpha Internexin: A Surrogate Marker for 1p/19q Codeletion and Prognostic Marker in Anaplastic (WHO grade III) Gliomas

Background: The WHO 2016 classification of diffuse gliomas has incorporated molecular markers isocitrate dehydrogenase (IDH) gene mutations (IDHmut) and codeletion of chromosomal arms 1p and 19q (1p/19q codeletion) as tumor defining entities. The diagnosis of diffuse oligodendrogliomas (ODG) and anaplastic oligodendroglioma (AO) mandatorily requires the demonstration of IDH1 and/or IDH2 mutations along with 1p/19q codeletion, whereas the 1p/19q noncodeleted diffuse gliomas are labeled as astrocytomas. The current methodologies for assessing 1p/19q codeletion status are expensive and not widely available. Studies have proposed alpha internexin (INA) expression on immunohistochemistry (IHC) as a surrogate marker for 1p/19q codeletion and a good prognostic marker in gliomas. Materials and Methods: In this study, we performed IHC for INA expression on the retrospective cohort of anaplastic gliomas (AGs) from our previously published study. Results: INA positivity on IHC showed a significant positive correlation with 1p/19q codeletion (P < 0.001) with a Spearman's rank correlation coefficient (Rho) of 0.804, sensitivity of 87.5%, specificity of 93.0%, and a diagnostic odds ratio of 93:1 in AGs. Similar to the 1p/19q codeletion status, INA positivity showed a positive correlation with IDHmut (P = 0.002) and a negative correlation with -thalassemia mental retardation X-linked protein (ATRX) loss of expression (P < 0.001). On univariate survival analysis, INA positivity was associated with significantly prolonged overall survival (OS) and recurrent free survival (RFS) in AGs (P < 0.001). Furthermore, within AO, INA positivity significantly improved RFS (P = 0.022) with OS trending towards significance (P = 0.094). Conclusions: INA expression on IHC could serve as a potential surrogate marker for 1p/19q, and highlights its prognostic value in AO and AGs.