title: Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group.
abstract: Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.
authors.affiliation: University Institute of Pathology, Lausanne, Switzerland. louis.guillou@chuv.ch
authors.forename: Louis
authors.initials: L
authors.lastname: Guillou
authors.forename: Jean
authors.initials: J
authors.lastname: Benhattar
authors.forename: Carole
authors.initials: C
authors.lastname: Gengler
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gallagher
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchère-Vince
authors.forename: Françoise
authors.initials: F
authors.lastname: Collin
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Terrier-Lacombe
authors.forename: Agnès
authors.initials: A
authors.lastname: Leroux
authors.forename: Bernard
authors.initials: B
authors.lastname: Marquès
authors.forename: Nicolas de Saint
authors.initials: Nde S
authors.lastname: Aubain Somerhausen
authors.forename: Frédérique
authors.initials: F
authors.lastname: Keslair
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D015622:Epithelioid Cells / Q000473:pathology*; D005260:Female; D005350:Fibroma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005354:Fibrosarcoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C485618:CREB3L1 protein, human; C518609:CREB3L2 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034702:RNA-Binding Protein FUS