title: Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study.
abstract: BACKGROUND
  Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis.
  
  
  METHODS
  In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information. For each case, the pathologist made one primary diagnosis followed by up to two differential diagnoses, based on histological characteristics only. Each diagnosis was classified as certain, probable, or possible. For each case to determine the molecular classification, we did fluorescence in-situ hybridisation on paraffin-embedded samples. We also did comparative genomic hybridisation and quantitative PCR (cohort 2) or reverse transcriptase PCR (cohorts 3-6) on frozen and paraffin-embedded samples. We made a final diagnosis based on the molecular results. The clinical effect of diagnosis correction was assessed by a board of experts.
  
  
  RESULTS
  Between June 22, 2009, and Oct 30, 2012, 395 patients were enrolled in the study, of which 384 were eligible for inclusion. The diagnosis was eventually modified by molecular genetics for 53 patients: eight (16%) of 50 patients with dermatofibrosarcoma (cohort 1), seven (23%) of 30 patients with dedifferentiated liposarcoma (cohort 2), 13 (12%) of 112 with Ewing's sarcoma family of tumours (cohort 3), 16 (16%) of 97 patients with synovial sarcoma (cohort 4), seven (15%) of 46 patients with alveolar rhabdomyosarcoma (cohort 5), and two (4%) of 49 patients with myxoid or round cell liposarcoma (cohort 6), with an effect on primary management or prognosis assessment in 45 cases.
  
  
  CONCLUSIONS
  Molecular genetic testing should be mandatory for diagnostic accuracy of sarcoma and appropriate clinical management, even when histological diagnosis is made by pathologist experts in this field.
  
  
  BACKGROUND
  French National Cancer Institute and Nice University Hospital.
authors.affiliation: Early Phase Trials and Sarcoma Units, Bergonie Cancer Institute, Bordeaux, France. Electronic address: a.italiano@bordeaux.unicancer.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Laboratory of Solid Tumor Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), Faculty of Medicine, University of Nice-Sophia-Antipolis, CNRS, Nice, France.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Di Mauro
authors.affiliation: Laboratory of Solid Tumor Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), Faculty of Medicine, University of Nice-Sophia-Antipolis, CNRS, Nice, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Rapp
authors.affiliation: Genetic Somatic Units, Institut Curie, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Department of Pathology and Medical Biology, Gustave-Roussy Institute, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auger
authors.affiliation: Department of Pathology, Leon Bérard Center, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alberti
authors.affiliation: Department of Pathology, Bergonié Cancer Institute, INSERM U916, University of Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chibon
authors.affiliation: Department of Biochemistry and Molecular Biology, Lille University Hospital, Lille, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Pathology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Voegeli
authors.affiliation: Department of Pathology, Paul Strauss Institute, Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ghnassia
authors.affiliation: Laboratory of Solid Tumor Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), Faculty of Medicine, University of Nice-Sophia-Antipolis, CNRS, Nice, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Keslair
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: Marick
authors.initials: M
authors.lastname: Laé
authors.affiliation: Department of Pathology, Leon Bérard Center, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchère-Vince
authors.affiliation: Department of Pathology and Medical Biology, Gustave-Roussy Institute, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Baffert
authors.affiliation: Department of Pathology, Bergonié Cancer Institute, INSERM U916, University of Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.affiliation: Laboratory of Solid Tumor Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), Faculty of Medicine, University of Nice-Sophia-Antipolis, CNRS, Nice, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055028:Comparative Genomic Hybridization; D018223:Dermatofibrosarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D008080:Liposarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D057089:Pathology, Molecular; D011379:Prognosis; D012509:Sarcoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins