Topoisomerase II-alpha protein expression and histological response following doxorubicin-based induction chemotherapy predict survival of locally advanced soft tissues XXXX .

@entity1 @entity11833 @entity242 @entity5 @entity1349 @entity1722
PURPOSE: Neoadjuvant chemotherapy for locally advanced soft @entity242 (LASTS), although not standard, represents a promising option for resectable @entity5 . Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), @entity1722 , @entity11833 ( @entity11833 ) protein expression, histological response and clinical outcomes of LASTS @entity1 . @entity1 AND METHODS: A retrospective study based on clinical data and archival paraffin-embedded @entity5 tissue at diagnosis from 78 consecutive LASTS @entity1 treated with neo-adjuvant chemotherapy in our institution enabled analysis of @entity11833 , @entity1722 and Topo2A protein expression by immuno-histochemistry. RESULTS: Disease free survival (DFS) and @entity1349 ( @entity1349 ) were 48% and 64%, respectively. The annual risk of relapse increased with a higher percentage of residual identifiable cells (RIC). A higher Topo2A protein was associated with an improved rate of good HR (r=0.416) and with a decreased risk of relapse. Median DFS decreased with low Topo2A (p   0.042). The @entity11833 status had no impact on histological response while @entity11833 positive @entity5 correlated with a favourable @entity1349 (p  <= 0.058). @entity1 with LASTS co-expressing Topo2A and @entity11833 had a significant better outcome (p=0.018). Topo2A was the only independent variable linked to a good HR (p  <= 0.017); histological grade 3 was the only independent adverse prognostic variable linked to both DFS (p  <= 0.04) and @entity1349 (p  <= 0.004). CONCLUSIONS: While histological response predicts better DFS, Topo2A protein expression correlates with histological response and better DFS. The combination of an early predictive factor for chemosensitivity (Topo2A) and for survival ( @entity11833 ) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).
