9580 Background: CXCR4 is overexpressed in many human tumors and plays important role in targeted metastasis. CXCR4 activation has been described in osteosarcoma, rhabdomyosarcoma and Ewing’s sarcoma both in vivo and in vitro, but its role has not been elucidated in SS yet. EGFR and Her2/neu, have been described to be overexpressed in patients with SS and proposed as potential therapeutic targets. Because CXCR4 and Her2 have been found to be functionally linked in breast cancer cell lines, we characterized SS in terms of CXCR4, Her2 and EGFR coexpression. Materials and Methods: Six patients sequentially observed at the Spedali Civili di Brescia from 1999 to 2005, with a diagnosis of synovial sarcoma were included in the study. The diagnosis of SS, a FISH analysis for t(X;18) was performed by using a commercial probe specific for the SYT gene breakpoint region (18q11) or by RT-PCR. Her2 and EGFR expression were determined by IHC and Her2 gene amplification by FISH analysis. CXCR4 expression was determined by IHC with anti-human CXCR4 monoclonal antibody (Clone 44716, R&D Systems) followed by incubation with the EnVision peroxidase kit (Dakocytomation, Glostrup, Denmark). Results: All patients were classified high-risk (stage III-IV) according to the AJCC/UICC VI Edition Staging System for soft tissue sarcomas. In all samples IHC analysis for Her2 was negative and no amplification was found by FISH. EGFR staining demonstrated positivity in 5 patients out of 6. CXCR4 reactivity was identified in 4 cases (nuclear staining in 3 and membrane staining in 1). CXCR4 and EGFR were coexpressed in 3 tumors. After a median follow-up of 24 months, 2 patients are dead of SS, 4 patients are alive, 3 of them are disease-free and one relapsed to the lung. The 3 patients alive and disease-free resulted positive for nuclear CXCR4 and EGFR while membrane CXCR4 was expressed in one dead patient. Conclusion: This study provides evidence that CXCR4 is expressed in cases of SS and is frequently coexpressed with EGFR but not with Her2. Due to the small size of this series it is not possible to establish any definitive prognostic or predictive value of CXCR4. However, nuclear expression of CXCR4 seems to be associated with a more indolent behaviour of the tumor and requires confirmation in larger series. No significant financial relationships to disclose.
Hsp90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin Prevents Synovial Sarcoma Proliferation via Apoptosis in In vitro Models
