Topoisomerase Ii-Alpha (Top2a) And Chromosome 17 Abnormalities In Locally Advanced Soft Tissue Sarcomas (Lasts)

10584 Background: High Top2A protein expression seems to be a relevant early predictive marker for good histologic response (GHR) and better PFS in patients (pts) with LASTS treated with doxorubicin-containing induction chemotherapy (CT) (Ruiz-Soto, ASCO 2007). Whether Top2A overexpression is related to TOP2A gene amplification or deletion and/or aneusomy of chromosome 17 (Chr 17) is unknown. Methods: Top2A IHC protein expression and gene Chr 17 anomalies by FISH analysis (TOP2A probe kit, DAKO, Denmark) were performed in paraffin embedded initial biopsies of LASTS pts treated with induction CT. FISH signals from 60 non overlapping intact tumoral nuclei were evaluated and the mean number signal/cell ratio was determined, TOP2A:centromere 17 (Cep 17) and Cep 17:number of cells ratios were calculated. TOP2A was considered amplified when the ratio was >1.85 and deleted when <0.80. Cep 17 levels between 1.5 and 2.25 were considered as disomic, those <1.5 as monosomic and >2.26 as polysomic. Results: Top2A median value was used to separate high and low Top2A expressing tumors. Of the 60 initial samples, 12 were discarded because of bad DNA quality and 25 have been studied so far. No predominant TOP2A amplifications were found, TOP2A was deleted in 2 cases; both were associated to Top2A protein overexpression and harbored Chr 17 anomalies as well. Aneusomy 17 was found in 10 (40%) of LASTS studied, 1 monosomy in a synovial sarcoma and polysomy in 9 cases. The monosomic sarcoma had low Top2A levels; seven polysomic LASTS overexpressed Top2A and 43% of disomic cases had higher levels of Top2A too. There was no significant correlation between Top2A protein expression and TOP2A or Chr 17 copy number anomalies. Seventy percent of aneusomic LASTS achieved GHR against 46% of disomic LASTS (NS). Of note, disomic LASTS have not achieved median PFS and OS versus 41 and 59 months respectively in aneusomic cases (NS). Conclusions: TOP2A gene and aneusomy 17 are not the sole biological events influencing Top2A protein overexpression in LASTS, the search for Top2A mutation and/or TOP2A altered gene regulation may be of relevance. These observations have to be validated in larger prospective studies. No significant financial relationships to disclose.