Abstract 19: Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features.

Introduction. Synovial sarcoma (SynSa) is an aggressive type of tumor, comprising approximately 10% of soft tissue sarcomas. Over half of SynSa patients develop metastases or local recurrence, but the molecular mechanism of aggressive SynSa outcome remains poorly characterized. Methods.Sixty five frozen tumor specimens from 54 SynSa patients [34 males; median age 37 years (range 5-86 years)] were subjected to aCGH and gene expression profiling. Examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (“SynSa1 group;" median follow-up 76 months), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (“SynSa2 group;" median follow-up 29 months), and 23 metastatic/recurrent SynSa tumors (“SynSa3 group;" median follow-up 46 months). For 8 patients primary tumor specimen was paired with metastatic/recurrent tumor specimens. Median follow-up for all patients was 40 months (range 3-218 months). Results. AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group (corr p = 4.48e-6 and corr p = 8.65e-6, respectively). Moreover, we identified 125 genes differentially expressed between SynSa1 and SynSa2 groups (t test unpaired, corr p value cut-off = 0.05, fold change ≥ 2), 38 of which were common with recently published CINSARC (Complexity Index in Sarcomas) prognostic signature (Ref. 1, 2). Comparison of expression profiles between SynSa2 and SynSa3 groups did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups (p = 0.021 and p = 0.020, respectively). The median GI in SynSa1, SynSa2 and SynSa3 groups was 9 (range 0-49), 16 (range 0-123) and 28 (range 0-130), respectively. Of note, there was no statistically significant difference in genome complexity between SynSa2 and SynSa3 groups, which suggests that progressive disease is not associated with accumulation of secondary genomic rearrangements/copy number changes. Conclusions. Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent SynSa. Presented data confirm that aggressive SynSa behavior is determined early in SynSa development and may be related to impaired mitotic regulatory mechanism. Citation Format: Joanna Przybyl, Raf Sciot, Agnieszka Wozniak, Patrick Schoffski, Vanessa Vanspauwen, Ignace Samson, Janusz A. Siedlecki, Piotr Rutkowski, Maria Debiec-Rychter. Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 19. doi:10.1158/1538-7445.AM2013-19