High Carbonic Anhydrase-9 Expression Identifies a Subset of 1p/19q Co-Deletion and Favorable Prognosis in Oligodendroglioma.

Abstract

To investigate the relationship between 3 hypoxic markers, carbonic anhydrase-9 (CA-9), hypoxia-inducible factor (HIF)-1α, and HIF-2α and the traditional genetic markers, deletions of chromosomes 1p and 19q and Isocitrate dehydrogenase 1 (IDH1) R132H mutation in oligodendrogliomas. Thirty-one oligodendrogliomas (27 World Health Organization Grade [WHO] II and 4 WHO Grade III) were processed into tissue microarray. Fluorescence in situ hybridization was exploited to detect chromosome deletion, whereas immunohistochemistry was performed to assess IDH1R132H mutation, CA-9, HIF-1α, and HIF-2α expression. The frequencies of 1p/19q co-deletion and IDH1 R132H mutation were 68% and 71%, respectively. High expression of CA-9 was observed in 42% and was associated with longer survival (P = 0.04) in WHO Grade II oligodendroglioma. High CA-9 expression also identified 62% of 1p/19q-codeleted oligodendroglioma (P = 0.001). In addition, all tumors with high CA-9 expression displayed 1p/19q-codeletion. HIF-1α and HIF-2α provided no additional prognostic value for survival. High expression of CA-9, a marker for hypoxia and acidosis, is associated with favorable prognosis in oligodendroglioma. In addition, it may serve as a simple screening test for 1p/19q co-deletion if validated in larger cohorts.