Abstract
Purpose: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). Methods: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. Results: Fourteen patients with SYT–SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT–SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31–p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21–q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (≥3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. Conclusion: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH.
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Antonescu CR, Kawai A, Leung DH, Lonardo F, Woodruff JM, Healey JH, Ladanyi M (2000) Strong association of SYT–SSX fusion type and morphologic epithelial differentiation in synovial sarcoma. Diagn Mol Pathol 9:1–8
Bruder CE, Hirvela C, Tapia-Paez I, Fransson I, Segraves R, Hamilton G, Zhang XX, Evans DG, Wallace AJ, Baser ME, Zucman-Rossi J, Hergersberg M, Boltshauser E, Papi L, Rouleau GA, Poptodorov G, Jordanova A, Rask-Andersen H, Kluwe L, Mautner V, Sainio M, Hung G, Mathiesen T, Moller C, Pulst SM, Harder H, Heiberg A, Honda M, Niimura M, Sahlen S, Blennow E, Albertson DG, Pinkel D, Dumanski JP (2001) High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH. Hum Mol Genet 10:271–282
Cadman NL, Soule EH, Kelly PJ (1965) Synovial sarcoma; an analysis of 34 tumors. Cancer 18:613–627
Choong PF, Rydholm A, Gustafson P (1995) Patients with soft-tissue sarcomas. Ann Surg 221:203–205
Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, 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 7:502–508
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 14:2333–2340
Dammann R, Schagdarsurengin U, Seidel C, Strunnikova M, Rastetter M, Baier K, Pfeifer GP (2005) The tumor suppressor RASSF1A in human carcinogenesis: an update. Histol Histopathol 20:645–663
Elias A, Ryan L, Sulkes A, Collins J, Aisner J, Antman KH (1989) Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 7:1208–1216
Enneking WF, Spanier SS, Goodman MA (1980) A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 153:106–120
Forus A, Florenes VA, Maelandsmo GM, Meltzer PS, Fodstad O, Myklebost O (1993) Mapping of amplification units in the q13–14 region of chromosome 12 in human sarcomas: some amplica do not include MDM2. Cell Growth Differ 4:1065–1070
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 338:153–160
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 53:5535–5541
Ladanyi M, Antonescu CR, Leung DH, Woodruff JM, Kawai A, Healey JH, Brennan MF, Bridge JA, Neff JR, Barr FG, Goldsmith JD, Brooks JS, Goldblum JR, Ali SZ, Shipley J, Cooper CS, Fisher C, Skytting B, Larsson O (2002) Impact of SYT–SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 62:135–140
Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B (1993) p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res 53:2231–2234
Mori O, Takagi K, Kitagawa T, Harada M, Ogawa I (1986) Combination chemotherapy with vincristin, actinomycin D, cyclophosphamide and adriamycin in soft-part sarcoma. Gan No Rinsho 32:998–1004
Nakagawa Y, Yoshida A, Numoto K, Kunisada T, Wai D, Ohata N, Takeda K, Kawai A, Ozaki T (2006) Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization. Oncol Rep 15:297–303
Oda Y, Sakamoto A, Satio T, Kawauchi S, Iwamoto Y, Tsuneyoshi M (2000) Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma. Mod Pathol 13:994–1004
Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80–83
Sardon D, de la Fuente I, Calonge E, Perez-Alenza MD, Castano M, Dunner S, Pena L (2005) H-ras immunohistochemical expression and molecular analysis of urinary bladder lesions in grazing adult cattle exposed to bracken fern. J Comp Pathol 132:195–201
Skytting BT, Szymanska J, Aalto Y, Lushnikova T, Blomqvist C, Elomaa I, Larsson O, Knuutila S (1999) Clinical importance of genomic imbalances in synovial sarcoma evaluated by comparative genomic hybridization. Cancer Genet Cytogenet 115:39–46
Smith SH, Weiss SW, Jankowski SA, Coccia MA, Meltzer PS (1992) SAS amplification in soft tissue sarcomas. Cancer Res 52:3746–3749
Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM (2000) Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 18:3794–3803
Szadowska A, Olborski B, Harezga-Bal B, Debiec-Rychter M (1999) Expression of P53, MDM2 and Ki-67 antigens in soft tissue sarcomas. Pol J Pathol 50:9–16
Szymanska J, Serra M, Skytting B, Larsson O, Virolainen M, Akerman M, Tarkkanen M, Huuhtanen R, Picci P, Bacchini P, Asko-Seljavaara S, Elomaa I, Knuutila S (1998) Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization. Genes Chromosomes Cancer 23:213–219
Verelst SJ, Hans J, Hanselmann RG, Wirbel RJ (2004) Genetic instability in primary leiomyosarcoma of bone. Hum Pathol 35:1404–1412
Wall N, Starkhammar H (2003) Chemotherapy of soft tissue sarcoma—a clinical evaluation of treatment over ten years. Acta Oncol 42:55–61
Wilke W, Maillet M, Robinson R (1993) H-ras-1 point mutations in soft tissue sarcomas. Mod Pathol 6:129–132
Wunder JS, Eppert K, Burrow SR, Gokgoz N, Bell RS, Andrulis IL (1999) Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas. Oncogene 18:783–788
Xie Y, Skytting B, Nilsson G, Grimer RJ, Mangham CD, Fisher C, Shipley J, Bjerkehagen B, Myklebost O, Larsson O (2002) The SYT–SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery. Oncogene 21:5791–5796
Zimmermann T, Blutters-Sawatzki R, Flechsenhar K, Padberg WM (2001) Peripheral primitive neuroectodermal tumor: challenge for multimodal treatment. World J Surg 25:1367–1372
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Supported in part by a Grant-in-Aid for Clinical Cancer Research and Grant-in-Aid for Cancer Research (14S-4 and -5) from the Ministry of Health, Labor and Welfare, Japan; by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports, and Culture (No. 14370464); and by a Grant-in-Aid from Japan Orthopaedics and Traumatology Foundation, Inc. (J.O.T.F. Grant No. 0134).
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Nakagawa, Y., Numoto, K., Yoshida, A. et al. Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization. J Cancer Res Clin Oncol 132, 444–450 (2006). https://doi.org/10.1007/s00432-006-0089-5
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DOI: https://doi.org/10.1007/s00432-006-0089-5