Abstract 5909: IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience
Authors: Setola Elisabetta , Benini Stefania , Righi Alberto , Gamberi Gabriella , Avnet Sofia , Carretta Elisa , Ferrari Cristina , Palmerini Emanuela , Lollini Pier Luigi , Cesari Marilena , Paioli Anna , Longhi Alessandra , Donati Davide Maria , Baldini Nicola 
Published: September 2020

Abstract
Purpose: 5-years overall survival (OS) in high grade conventional chondrosarcoma is about 50%. Grade has been identified as the main prognostic factor. Heterozigous isocitrate dehydrogenase (IDH) mutations are present in about half of conventional chondrosarcomas, with higher frequency in low grade lesions. IDH prognostic role is not fully understood. Aim of this study is to assess the frequency of IDH mutations in high grade chondrosarcoma, their relationship with clinical characteristics, and their prognostic role. Methods: patients who underwent surgery at Rizzoli between 2002 and 2012 with a diagnosis of G2- G3 conventional chondrosarcoma and fresh frozen tissue available were selected from archives. DNA extraction was performed with commercial kit. PCR amplification of exon 4 of IDH1 and IDH2 genes, and sequencing analysis with Sanger was performed. Results: 54 patients identified:18 (33%) were male, 36 (67%) female; median age was 62 (range 17-85 years). 40 (74%) patients had localized tumor, and 14 (26%) presented with metastases. Tumor was in the extremities in 25 (46%) patients. 41 (76%) of the cases were G2, 13 (24%) G3. 4 patients had a genetic predisposition (1 Maffucci syndrome and 3 Ollier disease). IDH mutation was detected in 26 (48%) of the patients (20 IDH1, 4 IDH2, and 2 patients both IDH1 and 2). Frequency of mutation was 17 (65%) in G2, and 9 (35%) in G3. 4/4 chondrosarcomas in with a syndrome presented a mutation. Gender, site and stage were not significantly different by mutational status. After a median follow-up of 124 months (range 1-166) the 5-year OS was 51% (95% CI:36-64), with no difference according to mutational status (5-year OS IDHmut 54% vs IDHwt 48%, p=0.45), and better survival for localized vs metastatic pts (68% vs 7%, p&lt;0.001), and for grade G2 vs G3 (59% vs 22%, p=0.0031). No difference in survival was observed for gender and site. In 25/27 patients with histological confirmation of recurrence/progression (21 cases G2, 4 G3), 27% of G2, IDHwt chondrosarcomas at initial diagnosis acquired higher grade in the recurrence, as compared with 50% in G2 IDHmut tumors. Conclusions: IDH mutations had higher frequency in G2 chondrosarcomas as compared to G3. No difference in OS according to mutational status was demonstrated. IDH mutated tumors had higher rate of grade progression at relapse, as compared to IDHwt. Confirmation of our results is needed in a larger series.
Citation Format: Elisabetta Setola, Stefania Benini, Alberto Righi, Gabriella Gamberi, Sofia Avnet, Elisa Carretta, Cristina Ferrari, Emanuela Palmerini, Pier Luigi Lollini, Marilena Cesari, Anna Paioli, Alessandra Longhi, Davide Maria Donati, Nicola Baldini. IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5909.