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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

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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.

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Abbreviations

SS:

synovial sarcoma

MFSS:

monophasic fibrous synovial sarcoma

BSS:

biphasic synovial sarcoma

PDSS:

poorly differentiated synovial sarcoma

TMA:

tissue microarray

RT-PCR:

reverse-transcriptase–polymerase chain reaction

EGFR:

epidermal growth factor receptor

SALL2:

SAL (drosophila)-like 2

IGFBP2:

insulin-like growth factor binding protein 2

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Acknowledgements

We thank Estela Pons, Alejo Sempere, Francesc Soler, Laura Martinez, and Jose Benavent for their expert technical assistance. Supported by a grant (PI-04/0822) from the FIS (Instituto Carlos-III, Madrid, Spain) and PROTHETS (prognosis and therapeutic targets of Ewing’s family of tumors; FP6 contract no. 503036).

Manish Mani Subramaniam received a personal grant from the Spanish Agency for International Cooperation (AECI), Ministry of External Affairs, Spain.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, University of Valencia, Valencia, Spain

    Manish Mani Subramaniam

  2. Department of Pathology, Medical School, University of Valencia, Avda. Blasco Ibañez, 17, 46010, Valencia, Spain

    Samuel Navarro, Antonio Pellin, Carmen Carda & Antonio Llombart-Bosch

  3. Molecular Biology Unit, Fundación Instituto Valenciano de Oncologia, Valencia, Spain

    Jose Antonio López-Guerrero

  4. Department of Technology, University of Jaume-I, Castellon, Spain

    Jose Antonio Heredia Alvaro & Pau Lluís Gozalbo Sabater

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  1. Manish Mani Subramaniam
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Correspondence to Antonio Llombart-Bosch.

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Subramaniam, M.M., Navarro, S., Pellin, A. et al. 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. Virchows Arch 449, 435–447 (2006). https://doi.org/10.1007/s00428-006-0271-9

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