title: Fluorescence in situ analysis of soft tissue tumor associated genetic alterations in formalin-fixed paraffin-embedded tissue.
abstract: No prospective studies are available to date evaluating the combined analysis of chromosomal alterations via interphase FISH in different soft tissue sarcoma (STS) subtypes. We tested 64 consecutive sarcoma specimens with FISH probes to detect aberrations specific for a given STS subtype. We first determined the translocation frequency in the specific STS subtypes in 48 tumors, with the primary pathological diagnosis as the gold standard. Subsequently, to evaluate sensitivity and specificity, all FISH probes were hybridized to 16 STS of hitherto unknown diagnosis. DDIT3 translocations occurred in 8/10 (80%) of myxoid liposarcomas. FOXO1 translocations were noted in 4/4 (100%) of alveolar but in none of 7 embryonal rhabdomyosarcomas. All 15 (100%) Ewing sarcomas/PNET and 4 clear cell sarcomas (4/4) harbored EWSR1 translocations. SS18 rearrangements were demonstrated in 8/9 (89%) synovial sarcomas. MDM2 amplification was noted in 7/8 (88%) atypical lipomatous tumors/well-differentiated and 3/3 (100%) dedifferentiated liposarcomas, respectively, but not in four pleomorphic liposarcomas. Sensitivities and specificities ranged from 80% to 100% and from 93% to 100%, respectively, with the highest values observed for FOXO1 (100% each). We conclude, therefore, that is possible to accurately predict the STS subtype using a panel of different subtype-specific FISH probes, thereby greatly facilitating the differential diagnosis of these tumors.
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. Electronic address: heike.horn@ikp-stuttgart.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Horn
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany; Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Allmanritter
authors.affiliation: Institute of Pathology, L'Ospedale San Raffaele, Milano, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Institute of Pathology, University Hospital of Mannheim, Mannheim, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Justus
authors.initials: J
authors.lastname: Müller
authors.affiliation: Institute of Pathology, University Hospital of Gießen and Marburg, Gießen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Staiger
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: Institute of Pathology, Caritas-Hospital, Bad Mergentheim, Germany.
authors.forename: M Michaela
authors.initials: MM
authors.lastname: Ott
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D005240:Feasibility Studies; D005404:Fixatives; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D005557:Formaldehyde; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005858:Germany; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016707:Tissue Fixation / Q000379:methods*; D051742:Transcription Factor CHOP / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; C497249:DDIT3 protein, human; C500986:EWSR1 protein, human; C085126:FOXO1 protein, human; D005404:Fixatives; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C093961:SS18 protein, human; D051742:Transcription Factor CHOP; D005557:Formaldehyde; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: FFPE; FISH; Prospective; Soft tissue sarcomas; Translocations