Evaluation of Immunohistochemical Expression of IDH, ATRX and Ki-67 in the Diagnosis and Classification of CNS Gliomas

Background: WHO blue book has emphasized on incorporating histopathological as well as molecular basis for accurately diagnosing and risk stratifying cases of brain gliomas. Using surrogate immunohistochemistry may substitute molecular testing especially in low-income countries.

Aim: this retrospective cohort study was carried out at the Pathology department, Tanta university to evaluate the immunohistochemical expression of IDH, ATRX and KI-67 in diagnosis and classification of brain gliomas.

Materials and methods: Two hundred and fifty (250) formalin-fixed paraffin-embedded tissue blocks from cases with CNS tumors were evaluated for immunohistochemical expression using IDH, ATRX and KI-67.

Results: In cases of diffuse gliomas; tumor types showed significant difference as regard age of patients (p<0.001), as well as IDH1 and ATRX immunohistochemical expression (p<0.001). The proliferation index of Ki-67 also showed significant difference amongst groups (p<0.001). One hundred and ninety-six cases of diffuse gliomas were classified following immunohistochemical staining into 89 IDH-mutant tumors (45.4%) and 107 IDH-wild type tumors (Glioblastomas) (54.6%). Eighty-nine cases of IDH-mutant gliomas were further sub classified based on cell of origin and WHO grade into astrocytomas; grades 2, 3 and 4, as well as oligodendrogliomas; grades 2 and 3. In cases of localized gliomas; No significant data were detected as regard age of affected patients, or tumor location. All cases showed negative staining for IDH1 and retained nuclear expression for ATRX. The proliferation index showed variance amongst tumors (p<0.001). A comparison group of patients with reactive gliosis was also studied and showed negative staining for IDH1, retained ATRX expression with low Ki-67 proliferation index.

Conclusions: IDH, ATRX and Ki-67 may be beneficial in categorizing and properly diagnosing patients with brain tumors; which may serve not only as a surrogate for molecular testing, but also can guide therapeutic decisions.