Diagnostics of <i>IDH1/2</i> Mutations in Intracranial Chondroid Tumors: Comparison of Molecular Genetic Methods and Immunohistochemistry

Abstract

Intracranial chondroid tumors are a heterogeneous group of neoplasms characterized by the presence of a cartilage matrix. These tumors exhibit overlapping clinical and histological features. Mutations in IDH1/2 genes serve as important diagnostic markers of tumor type, particularly chondrosarcoma. To improve the accuracy of IDH1/2 diagnostics, we compared three methods: biochip assay, real-time PCR with DNA melting analysis using TaqMan probes and sequencing (qPCR-DMA-Sanger), and immunohistochemistry (IHC). Tumor samples from 96 patients were investigated. The IDH1 mutations were detected in 34/64 (53%) chondrosarcomas; IHC detected 27/56 (48.2%) mutations, the qPCR-DMA-Sanger method 27/59 (46%) mutations, and the biochip assay revealed 29/60 (48.3%) mutations. The detection of IDH1 mutations in chordoma (2/15) and osteosarcoma (2/7) suggested the need for a revised diagnosis. In benign tumors, IDH1 mutations were present in chondroma (4/6), but absent in chondromyxoid fibroma (0/4). The most frequent IDH1 mutations were R132C (60%), R132L, and R132G (13.5% each), R132H (8%), and R132S (5%). The concordance between the biochip assay and IHC was 90%, between IHC and PCR-DMA-Sanger 83%, and between biochip assay and qPCR-DMA-Sanger was 98%, respectively. No IDH2 mutations were found. The use of independent diagnostic methods may improve the detection of IDH-mutant specimens in chondroid tumors.

Keywords

• intracranial chondroid tumors
• <i>IDH1/2</i> mutations
• diagnostics
• immunohistochemistry
• biochip assay
• DNA melting analysis