Molecular Distinction of Chondrosarcoma from Chondroblastic Osteosarcoma through IDH12 Mutations
Darcy A Kerr, Vikram Deshpande, Darrell R Borger, G Petur Nielsen. Massachusetts General Hospital, Boston, MA
Background: Distinguishing chondrosarcoma from chondroblastic osteosarcoma particularly on a biopsy specimen can be difficult and highly subjective. This distinction is critical in determining the most appropriate treatment modality, since adjuvant chemotherapy is standard treatment for osteosarcoma while chondrosarcoma is generally treated by surgical excision alone. Cartilaginous neoplasms have recently been shown to frequently (56%) harbor mutations in the metabolic enzymes IDH1 and IDH2 (IDH1 > IDH2), whereas a wide range of other mesenchymal tumors have not. The purpose of this study was to analyze if the presence of IDH1/2 mutations can be used to distinguish between chondrosarcoma and chondroblastic osteosarcoma.
Design: 7 predominantly high grade chondrosarcoma tumors and 19 osteosarcoma tumors (12 purely chondroblastic, 7 mixed chondroblastic) were reviewed and DNA was extracted from formalin-fixed, paraffin-embedded tissue. Mutational analysis using a multiplexed PCR genotyping platform was used to query for hotspot mutations in the genes IDH1 at codon R132 and IDH2 at codon R140. IDH1 negative cases underwent Sanger sequencing of IDH2 exon 4.
Results: A total of 6 chondrosarcomas and 17 osteosarcomas yielded DNA of sufficient quality for analysis. No osteosarcomas and 67% of chondrosarcomas (4/6) harbored a somatic mutation in IDH1. No chondrosarcomas and two of 17 osteosarcomas showed a somatic IDH2 mutation. On further pathological review, one of the IDH2 mutant osteosarcoma cases was actually a dedifferentiated chondrosarcoma with an osteosarcomatous component. The second IDH2 mutant osteosarcoma case was an unequivocal chondroblastic and osteoblastic osteosarcoma arising in a 12-year-old girl. Of note, the particular IDH2 mutation (R159C) found in this latter case has not previously been reported and is of unknown biological significance.
Conclusions: IDH1/2 mutation analysis appears to be a promising biomarker for the distinction of chondrosarcoma from chondroblastic osteosarcoma. Our work is consistent with the previous observation that among mesenchymal tumors, mutations in IDH1 thus far appear restricted to cartilaginous neoplasms. However our series found one IDH2 mutation in an osteosarcoma. Analysis of additional cases and testing for accumulation of the distinctive oncometabolite will help further elucidate the significance of these findings.
Category: Bone & Soft Tissue
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 8, Tuesday Morning