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01-10-2006 | Original Article

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

Authors: Manish Mani Subramaniam, Samuel Navarro, Antonio Pellin, Jose Antonio López-Guerrero, Carmen Carda, Jose Antonio Heredia Alvaro, Pau Lluís Gozalbo Sabater, Antonio Llombart-Bosch

Published in: Virchows Archiv | Issue 4/2006

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.

Allander SV, Illei PB, Chen Y, Antonescu CR, Bittner M, Ladanyi M, Meltzer PS (2002) Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 161:1587–1595PubMed

Alonso SR, Ortiz P, Pollan M, Perez-Gomez B, Sanchez L, Acuna MJ, Pajares R, Martinez-Tello FJ, Hortelano CM, Piris MA, Rodriguez-Peralto JL (2004) Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. Am J Pathol 164:193–203PubMed

Antonescu CR, Leung DH, Dudas M, Ladanyi M, Brennan M, Woodruff JM, Cordon-Cardo C (2000) Alterations of cell cycle regulators in localized synovial sarcoma: a multifactorial study with prognostic implications. Am J Pathol 156:977–983PubMed

Bubendorf L, Kolmer M, Kononen J, Koivisto P, Mousses S, Chen Y, Mahlamaki E, Schraml P, Moch H, Willi N, Elkahloun AG, Pretlow TG, Gasser TC, Mihatsch MJ, Sauter G, Kallioniemi OP (1999) Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays. J Natl Cancer Inst 91:1758–1764PubMedCrossRef

Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, Bianco AR, Tortora G (1999) Antitumor effects and potentiation of cytotoxic drug activity in human cancer cells by ZD1839 (“Iressa”), an EGFR-selective tyrosine kinase inhibitor. Clin Cancer Res 6(5):2053–2063

Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AML, Gusterson BA, Cooper CS (1994) Identification of novel genes, SYT and SSX, involved in the t(X, 18) (p11.2; q11.2) translocation found in human synovial sarcoma. Nat Genet 7:502–508PubMedCrossRef

Coindre JM, Pelmus M, Hostein I, Lussan C, Bui BN, Guillou L (2003) Should molecular testing be required for diagnosing synovial sarcoma? A prospective study of 204 cases. Cancer 98:2700–2707PubMedCrossRef

Crew AJ, Clark J, Fisher C, Gill S, Grimer R, Chand A, Shipley J, Gusterson BA, Cooper CS (1995) Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J 2333–2340

Donhuijsen K, Budach V, van Beuningen D, Schmidt U (1988) Instability of xenotransplanted soft tissue sarcomas. Morphologic and flow cytometric results. Cancer 61:68–75PubMedCrossRef

10.

Engelholm SA, Brunner N, Spang-Thompsen M, Vindlov L (1982) Genetic instability of human solid tumors growth in nude mice. In: Sordat B (ed) Immune deficient animals: 4th international workshop on immunodeficient animals in experimental research, Chexbres. Karger, Basel, pp 339–344

11.

Farris KB, Reed RJ (1982) Monophasic, glandular, synovial sarcomas and carcinomas of the soft tissues. Arch Pathol Lab Med 106:129–132PubMed

12.

Fisher C (1998) Synovial sarcoma. Ann Diagn Pathol 2:401–421PubMedCrossRef

13.

Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang R, Bruner JM, Yung WK, Zhang W (1999) Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. Cancer Res 59:4228–4232PubMed

14.

Guillou L, Coindre J, Gallagher G, Terrier P, Gebhard S, de Saint Aubain Somerhausen N, Michels J, Jundt G, Vince DR, Collin F, Trassard M, Le Doussal V, Benhattar J (2001) Detection of the synovial sarcoma translocation t(X;18) (SYT-SSX) in paraffin embedded tissues using reverse transcriptase–polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives. Hum Pathol 32:105–112PubMedCrossRef

15.

Hajdu SI, Lemos LB, Kozakewich H, Helson L, Beattie EJ Jr (1981) Growth pattern and differentiation of human soft tissue sarcomas in nude mice. Cancer 47:90–98PubMedCrossRef

16.

Hoos A, Urist MJ, Stojadinovic A, Mastorides S, Dudas ME, Leung DH, Kuo D, Brennan MF, Lewis JJ, Cordon-Cardo C (2001) Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors. Am J Pathol 158:1245–1251PubMed

17.

Ishii S, Yamawaki S, Saki T, Usui M, Ubayama Y, Minami A, Yagi T, Isu K, Kobayashi M (1983) Characteristics of human soft tissue sarcomas in xenografts and in vitro. Clin Orthop Relat Res 173:251–261PubMed

18.

Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG (2002) SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones. J Biol Chem 277:5498–5505PubMedCrossRef

19.

Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M (1998) SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 338:153–160PubMedCrossRef

20.

Kawai A, Naito N, Yoshida A, Morimoto Y, Ouchida M, Shimizu K, Beppu Y (2004) Establishment and characterization of a biphasic synovial sarcoma cell line, SYO-1. Cancer Lett 204:105–113PubMedCrossRef

21.

Kawauchi S, Fukuda T, Oda Y, Saito T, Oga A, Takeshita M, Yokoyama K, Chuman H, Iwamoto Y, Sasaki K, Tsuneyoshi M (2000) Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins. Mod Pathol 13:755–765PubMedCrossRef

22.

Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ, Look AT (1993) Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res 53:5535–5541PubMed

23.

Kohlhase J, Schuh R, Dowe G, Kuhnlein RP, Jackle H, Schroeder B, Schulz-Schaeffer W, Kretzschmar HA, Kohler A, Muller U, Raab-Vetter M, Burkhardt E, Engel W, Stick R (1996) Isolation, characterization and organ specific expression of 2 novel human zinc finger genes related to Drosophilia gene spalt. Genomics 38:291–298PubMedCrossRef

24.

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMedCrossRef

25.

Lasota J, Jasinski M, Debiec-Rychter M, Szadowska A, Limon J, Miettinen M (1998) Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed paraffin embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma. Mod Pathol 11:626–633PubMed

26.

Llombart-Bosch A, Carda C, Boix J, Pellin A, Peydro-Olaya A (1988) Value of nude mice xenografts in the expression of cell heterogeneity of human sarcomas of bone and soft tissue. Pathol Res Pract 183:683–692PubMed

27.

Mendelsohn J (1997) Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin Cancer Res 3:2703–2707PubMed

28.

Nagai M, Tanaka S, Tsuda M, Endo S, Kato H, Sonobe H, Minami A, Hiraga H, Nishihara H, Sawa H, Nagashima K (2001) Analysis of transforming activity of human synovial sarcoma–associated chimeric protein SYT-SSX1 bound to chromatin remodelling factor Hbrm/ Hsnf2 alpha. Proc Natl Acad Sci USA 98:3843–3848PubMedCrossRef

29.

Naito N, Kawai A, Ouchida M, Dan’ura T, Morimoto Y, Ozaki T, Shimizu K, Inoue H (2000) A reverse transcriptase–polymerase chain reaction assay in the diagnosis of soft tissue sarcomas. Cancer 89:1992–1998PubMedCrossRef

30.

Nielsen TO, Hsu FD, O’Connell JX, Gilks CB, Sorensen PH, Linn S, West RB, Liu CL, Botstein D, Brown PO, van de Rijn M (2003) Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology. Am J Pathol 163:1449–1456PubMed

31.

Noguchi SI, Ueki T, Kawauchi S, Fukuda T, Matsuura H, Sonoda T, Tsuneyoshi M (1997) Establishment and characterization of a new synovial sarcoma cell line, SN-SY-1: special reference to bcl-2 protein and SYT-SSX1 hybrid transcripts. Int J Cancer 72:995–1002PubMedCrossRef

32.

Nojima T, Wang YS, Abe S, Matsuno T, Yamawaki S, Nagashima K (1990) Morphological and cytogenetic studies of a human synovial sarcoma xenotransplanted into nude mice. Acta Pathol Jpn 40:486–493PubMed

33.

Pelmus M, Guillou L, Hostein I, Sierankowski G, Lussan C, Coindre JM (2002) Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol 26:1434–1440PubMedCrossRef

34.

Roholl PJ, Rutgers DH, Rademakers LH, De Weger RA, Elbers JR, Van Unnik JA (1988) Characterization of human soft tissue sarcomas in nude mice: evidence for histogenic properties of malignant fibrous histiocytomas. Am J Pathol 131:559–568PubMed

35.

Rygaard J, Povelsen CO (1969) Heterotransplantation of human malignant tumor to “nude mice.” Acta Pathol Microbiol Scand 77:758–760PubMed

36.

Saito T, Oda Y, Kawaguchi K, Sugimachi K, Yamamoto H, Tateishi N, Tanaka K, Matsuda S, Iwamoto Y, Ladanyi M, Tsuneyoshi M (2004) E-Cadherin mutation and snail overexpression as alternative mechanisms of E-cadherin inactivation in synovial sarcoma. Oncogene 23:8629–8638PubMedCrossRef

37.

Sato A, Matsumoto Y, Koide U, Kataoka Y, Yoshida N, Yokota T, Asashima M, Nishinakamura R (2003) Zinc finger protein sall2 is not essential for embryonic and kidney development. Mol Cell Biol 23:62–69PubMedCrossRef

38.

Sokal RR, Michener CDA (1958) Statistical method for evaluating systematic relationships. Univ Kans Sci Bull 38:1409–1438

39.

Van de Rijn M, Barr FG, Xiong QB, Hedges M, Shipley J, Fisher C (1999) Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features. Am J Surg Pathol 23:106–112PubMedCrossRef

40.

Weiss SW, Goldblum JR (2001) Malignant soft tissue tumors of uncertain type. In: Weiss SW, Goldblum JR (eds) Enzinger and Weiss’s soft tissue tumors, 4th edn. Mosby, St Louis, pp 1483–1572

41.

West RB, Harvell J, Linn SC, Liu CL, Prapong W, Hernandez-Boussard T, Montgomery K, Nielsen TO, Rubin BP, Patel R, Goldblum JR, Brown PO, van de Rijn M (2004) Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol 28:1063–1069PubMedCrossRef

42.

Xie Y, Skytting B, Nilsson G, Brodin B, Larsson O (1999) Expression of insulin-like growth factor-1 receptor in synovial sarcoma: association with an aggressive phenotype. Cancer Res 59:3588–3591PubMed

43.

Yakushiji T, Yonemura K, Tsuruta J, Nishida K, Kato T, Takagi K (2000) Capacity for epithelial differentiation in synovial sarcoma: analysis of a new human cell line. J Clin Pathol 53:525–531PubMedCrossRef

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
Authors: Manish Mani Subramaniam
Samuel Navarro
Antonio Pellin
Jose Antonio López-Guerrero
Carmen Carda
Jose Antonio Heredia Alvaro
Pau Lluís Gozalbo Sabater
Antonio Llombart-Bosch
Publication date: 01-10-2006
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 4/2006
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-006-0271-9

2024 ASCO Annual Meeting

Springer Medicine

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

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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