Immunohistochemical expression of IDH1 in gliomas: a tissue microarray-based approach

Area of Science:

• Neuro-oncology
• Molecular pathology
• Cancer genetics

Background:

• Mutations in isocitrate dehydrogenase 1 (IDH1) are implicated in glioma development.
• Assessing IDH1 mutation frequency is crucial for glioma classification and understanding pathogenesis.

Purpose of the Study:

• To determine the frequency of IDH1 R132H point mutations in a series of 184 glioma cases.
• To evaluate the utility of immunohistochemistry for detecting IDH1 mutations in formalin-fixed, paraffin-embedded (FFPE) tissues.

Main Methods:

• A tissue microarray (TMA) was constructed from 195 glioma samples, including pilocytic astrocytoma (PA), diffuse astrocytoma (DA), glioblastoma multiforme (GBM), oligodendroglioma (OLIG), and ependymoma (EPEN).
• Immunohistochemical staining for IDH1, p53, and EGFR was performed on FFPE tissue samples using the labeled streptavidin avidin biotin (LSAB) method.

Main Results:

• The overall frequency of detectable IDH1 mutations was 15.8% (29/184) in evaluable tumors.
• IDH1 expression was observed in 42.5% of DA, 22.7% of OLIG, and 9.7% of GBM cases.
• Secondary GBM (sec-GBM) showed a high rate of IDH1 expression (85.7%), contrasting with primary GBM (prim-GBM) (1.5%). PA and EPEN did not show IDH1 reactivity. Positive correlation was noted between DA and GBM with p53, while IDH1 and EGFR coexpression was rare.

Conclusions:

• Monoclonal antibody to IDH1 (R132) offers a less labor-intensive and effective method for detecting IDH1 mutations in gliomas.
• IDH1 serves as a valuable immunohistochemical marker for distinguishing low-grade astrocytoma from reactive gliosis, potentially acting as an independent prognostic marker.
• IDH1 immunohistochemistry aids in differentiating primary from secondary GBM, though further validation with sequencing and clinical data is recommended.