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IDH mutations in older patients with diffuse astrocytic gliomas
Cyril Andrews1, Richard A Prayson1
1University School and Cleveland Clinic Department of Anatomic Pathology, USA.
Annals of Diagnostic Pathology
|November 2, 2020
Summary
Isocitrate dehydrogenase (IDH) mutations are key in diffuse astrocytic gliomas, but testing needs refinement for older adults. Follow-up PCR testing is crucial for older patients whose tumors are negative by standard immunohistochemistry to detect all IDH mutations.
Area of Science:
- Neuro-oncology
- Molecular diagnostics
- Cancer classification
Background:
- Isocitrate dehydrogenase (IDH) mutation status is vital for classifying diffuse astrocytic gliomas, influencing prognosis.
- Previous studies on routine IDH testing in older patients yielded conflicting recommendations regarding age-based algorithms.
- IDH mutations are established markers for oligodendrogliomas and predict better outcomes in diffuse astrocytic gliomas.
Purpose of the Study:
- To investigate the prevalence of IDH mutations in diffuse astrocytic gliomas across different WHO grades.
- To analyze the relationship between patient age and IDH mutation status in this cohort.
- To evaluate the efficacy of standard immunohistochemistry versus polymerase chain reaction (PCR) testing for IDH mutation detection in older patients.
Main Methods:
- Analysis of 381 diffuse astrocytic gliomas (53 WHO grade II, 66 WHO grade III, 262 WHO grade IV) for IDH mutation status.
- Initial screening using immunohistochemistry for IDH-1 (R132H) antibody.
- Follow-up PCR testing for IDH-1 and IDH-2 mutations in cases with negative immunohistochemistry staining.
Main Results:
- IDH mutations were found in 50.1% of grade II, 54.4% of grade III, and 15.1% of grade IV tumors.
- Tumors from patients under 55 years old showed higher IDH mutation rates compared to those 55 years and older.
- In patients 55 years and older, PCR testing identified non-IDH-1 (R132H) mutations in grade III (3/11) and grade IV (26/37) gliomas that were missed by immunohistochemistry.
Conclusions:
- While IDH mutations are more common in younger patients with diffuse astrocytic gliomas, a significant proportion of older patients harbor these mutations.
- Routine immunohistochemistry alone may miss IDH mutations in a notable subset of elderly patients.
- Follow-up PCR testing is recommended for all diffuse astrocytic gliomas negative by immunohistochemistry, especially in older individuals, to ensure accurate IDH mutation detection.
