Prognostic stratification of gliomatosis cerebri by IDH1^R132H and INA expression

Gliomatosis cerebri (GC) constitutes a heterogenous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1^R132H mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1^R132H and 10/40 GC expressed INA. IDH1^R132H staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1^R132H vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1^R132H and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1^R132H mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.