Reproducibility of Molecular Analysis in Soft Tissue Sarcomas and GIST: A Report from CONTICANET Network of Excellence
AP Dei Tos, MC Montesco, I Hostein, L Toffolatti, F Chibon, D Pissaloux, L Alberti, E Lazzari, D Ranchere-Vince, CR Rossi, I Ray-Coquard, JY Blay, JM Coindre. General Hospital, Treviso, Italy; University of Padua School of Medicine, Padua, Italy; Institut Bergonié, Bordeaux, France; Centre Léon Bérard, Lyon, France
Background: Molecular analysis and molecular genetics is being gradually implemented in the diagnostic workout of soft tissue sarcomas and GIST. Data regarding reproducibility as well as variability of molecular testing are lacking. A study has been performed within the Conticanet European Network of Excellence in order to evaluate the degree of concordance of molecular testing across three european referral laboratories.
Design: All soft tissue and visceral sarcomas (804 cases) occurring in 3 european regions (Veneto Italy, Aquitaine and Rhone-Alpes, France) have been collected prospectively during 2007. All cases of GIST and all cases of sarcoma in which a translocation was suspected were analyzed by FISH and RT qPCR. 10 GIST and one to every 10 sarcomas have been circulated among the three partners 44 cases (25 GIST and 19 sarcomas with a suspicion of translocation) were molecularly analysed. In 43 additional cases the results of FISH versus RT qPCR were compared. In 21 cases molecular tests were s also performed and compared on both frozen and FFPE material.
Results: Among GIST, 96% concordance was observed (one exon 18 PDGFRA mutation not detected in one region). Among sarcomas (10 synovial sarcomas, 4 myxoid liposarcomas, 2 rhabdomyosarcomas, 2 clear cell sarcomas, and 1 desmoplastic tumour) 89% concordance was observed. Discordances were in 2 myxoid liposarcoma (DDIT3/FUS translocation detected in two regions not confirmed in one region). 43 cases were evaluated for translocations by both RT-qPCR and FISH: 15 synovial sarcomas, 12 myxoid liposarcoma, 9 low grade fibromyxoid sarcoma, 4 Ewing's sarcoma/PNET and 3 alveolar rhabdomyosarcoma. Only one discordance was observed (one negative RT-PCR/positive FISH myxoid liposarcoma) however, 2 cases were not interpretable by RT-PCR as compared to 7 cases by FISH. Non discrepancies were observed between frozen and FFPE specimens.
Conclusions: The level of concordance of molecular testing among the three referral centers is remarkably high. The discrepancy observed in myxoid liposarcoma may be due to higher technical complexity. RT-PCR appears more sensitive than FISH in detecting sarcoma translocations. Molecular analysis performs optimally in both frozen and FFPE material.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 26, Monday Afternoon