title: Tissue microarray profiling of primary and xenotransplanted synovial sarcomas demonstrates the immunophenotypic similarities existing between SYT-SSX fusion gene confirmed, biphasic, and monophasic fibrous variants.
abstract: This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue microarray (TMA) evaluation of the immunophenotypic and histological progression of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs, and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a similar undifferentiated phenotype with loss of glandular component in the xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary tumors and xenografts. Enhanced bcl-2 and bax expression were noted in xenografts. Ki-67 overexpression in xenografts correlated with high mitotic index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in all original and xenografted SSs. Hierarchical clustering differentiated original MFSS and BSS, but their xenografts clustered together due to similar immunoexpression profile. Our study demonstrates definite phenotypic variability of BSS and MFSS in the xenografts. Differences in immunoexpression for various markers existed between primary tumor and xenografts but not between subtypes. Hierarchical clustering grouped TMA immunostaining data and confirmed immunophenotypic variability; however, it failed to reveal any immunophenotypic differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reverse-transcriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Manish Mani
authors.initials: MM
authors.lastname: Subramaniam
authors.forename: Samuel
authors.initials: S
authors.lastname: Navarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellin
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: López-Guerrero
authors.forename: Carmen
authors.initials: C
authors.lastname: Carda
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Heredia Alvaro
authors.forename: Pau Lluís
authors.initials: PL
authors.lastname: Gozalbo Sabater
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C116512:SYT-SSX fusion protein