Pax3/7-Foxo1 Fusions By Fluorescent In Situ Hybridization (Fish) Using An Adult Rhabdoinyosarcoina Tissue Microarray

10066 Background: Rhabdomyosarcomas (RMS) are rare, heterogeneous, small cell sarcomas. While RMS is a common type of childhood malignancy, few large studies focus on molecular cytogenetics of adult RMS. In pediatric alveolar RMS, patients with PAX3-FOXO1 gene fusion have an inferior prognosis, as compared to those patients whose tumor expresses the PAX7-FOXO1 fusion. We studied a large panel of adult RMS patients to determine whether the PAX3/7-FOXO1 fusions could be detected and whether there was any prognostic significance. Methods: From a database of 251 RMS patients followed at UT M. D. Anderson Cancer Center (1957-2001), 105 tissue samples were available for a histological, immunohistochemical and clinical evaluation. These samples were formatted into a tissue microarray (TMA) and fluorescent in situ hybridization (FISH) using break-apart probes for PAX3, PAX7 and FOXO1 was employed. The results were correlated with patient outcome using the log-rank test via Prism software. Results: Of the 104 samples analyzed, FISH was evaluable in 53 cases. The PAX3-FOXO1 fusion was found in 28%, PAX7-FOXO1 in 8%, and no fusion in 64% of these cases. Among the histologically defined alveolar RMS specimens, 11 (55%) had a fusion, mostly PAX3-FOXO1 (8). No fusion was detected in the pleomorphic subtype. The PAX3/7-FOXO1 translocation was detected in 8 adult, histologically defined embryonal RMS cases. Fusion status did not correlate with survival (PAX3-FOXO1: 26 months vs. PAX7-FOXO1: 28 months, p= 0.70). However, patients with metastatic disease were found to have a difference favoring better outcomes for those with translocation involving PAX3 (PAX3-FOXO1: 24 months vs. PAX7-FOXO1: 16 months, p= 0.48) that did not reach statistical significance. Conclusions: It is possible to detect PAX3/7-FOXO1 fusion by FISH analysis in a RMS TMA. The failure rate of hybridization (36%) is likely multifactorial but partly due to the fact that these specimens were older than 2 years of age, that should be considered. Additional studies are required to determine the role of PAX3/7-FOXO1 fusions for adult patients and the optimal detection method requested. No significant financial relationships to disclose.