Cancer Detection and Prevention 28 (2004) 294–301 Are there geographical differences in the frequency of SYT-SSX1 and SYT-SSX2 chimeric transcripts in synovial sarcoma? Ira Kokovi´ c, MSc a,∗ , Matej Braˇ cko, MD, PhD a , Rastko Golouh, MD, PhD a , Marjolijn Ligtenberg, PhD b , Han J.J.M. van Krieken, MD, PhD b , Petra Hudler, MSc c , Radovan Komel, PhD c a Department of Pathology, Institute of Oncology, Zaloˇ ska 2, SI-1000 Ljubljana, Slovenia b Department of Pathology, UMC St Radboud, HB-6500 Nijmegen, The Netherlands c Faculty of Medicine, Medical Center for Molecular Biology, Institute of Biochemistry, Vrazov trg 2, SI-1000 Ljubljana, Slovenia Abstract Synovial sarcoma (SS) is characterized by the t(X;18)(p11.2;q11.2) chromosomal translocation, which results in generating either SYT- SSX1, SYT-SSX2 or, infrequently, SYT-SSX4 fusion gene. The ratio of SYT-SSX1:SYT-SSX2 fusions is close to 2:1 in the majority of studies, and SYT-SSX2 fusion has been only rarely observed in biphasic SS. In the present study, we compared two series of patients with SS, Slovenian (37 cases) and Dutch (14 cases), with respect to clinical, pathological and molecular findings. The two groups did not differ with regard to clinicopathological features. Whereas the frequency of different SYT-SSX fusions in the Dutch group was similar to that reported in the literature, we found an unexpectedly high number of tumors with SYT-SSX2 fusion in the Slovenian group. The ratio of SYT-SSX1:SYT-SSX2 fusion was 7:18 for monophasic and 2:7 for biphasic tumors in the Slovenian group. This distribution differs significantly from that observed in the Dutch group in the present study (P = 0.041) as well as from data reported in the recent large multi-institutional study on 243 patients (P = 0.0001). Our findings indicate possible geographical differences in the frequency of two SYT-SSX fusion transcripts in patients with synovial sarcoma. © 2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. Keywords: Synovial sarcoma; SYT-SSX fusions; Histology; Geographical difference 1. Introduction Synovial sarcoma is highly malignant soft tissue tumor, which preferentially affects young adults and children [1–3]. This tumor accounts for 5–10% of soft tissue tumors and is mainly located in the extremities [1,4]. In more than half of the cases metastases develop, primarily in the lungs, but also in the lymph nodes and bone marrow [1]. More than a quar- ter of patients succumb to this cancer in the first 5 years after diagnosis, despite the best currently available management [5,6]. Histologically, synovial sarcomas are usually divided into three subtypes: biphasic (BSS), the most typical, but less common subtype, containing both epithelial and spindle ∗ Corresponding author. Tel.: +386 1 4322 099; fax: +386 1 5879 400. E-mail addresses: inkokovic@siol.net, ikokovic@onko-i.si (I. Kokovi´ c). cells, monophasic (MSS) subtype composed solely of spin- dle cells or, in rare cases, solely of epithelial-like cells, and poorly differentiated (PDSS) subtype, composed of primitive looking oval or spindle-shaped cells [1,2]. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11.2;q11.2) chromosomal translocation in more than 95% of cases [7]. Through this translocation the SYT gene on chromosome 18 is fused with a member of the SSX gene family on chromosome X, resulting in the generation of either SYT-SSX1, SYT-SSX2 [8,9,10] or rarely SYT-SSX4 fusion gene [7,11]. The SYT gene is widely expressed in human tissues and encodes a protein with transcription activation domain rich in glutamine, proline, glycine and tyrosine (QPGY domain) [12,13]. The SSX gene family contains at least six highly homologous members, which normally have a tissue specific expression restricted to 0361-090X/$30.00 © 2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.cdp.2004.06.002