TY - JOUR
T1 - Topoisomerase II-alpha protein expression and histological response following doxorubicin-based induction chemotherapy predict survival of locally advanced soft tissues sarcomas
AU - Rodrigo, Ruiz Soto
AU - Nathalie, Auger
AU - Elodie, Tournay
AU - Gonzalo, Gomez Abuin
AU - Philippe, Terrier
AU - Franoise, Drusch
AU - Julien, Domont
AU - Angela, Cioffi
AU - Bérénice, Boulet
AU - Jean-Yves, Blay
AU - Jean-Michel, Coindre
AU - Jean, Bénard
AU - Sylvie, Bonvalot
AU - Axel, Le Cesne
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Purpose: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas (LASTS), although not standard, represents a promising option for resectable tumours. Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), HER2, excision repair cross-complementing group 1 (ERCC1) protein expression, histological response and clinical outcomes of LASTS patients. Patients and methods: A retrospective study based on clinical data and archival paraffin-embedded tumour tissue at diagnosis from 78 consecutive LASTS patients treated with neo-adjuvant chemotherapy in our institution enabled analysis of ERCC1, HER2 and Topo2A protein expression by immuno-histochemistry. Results: Disease free survival (DFS) and overall survival (OS) 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 ERCC1 status had no impact on histological response while ERCC1 positive tumours correlated with a favourable OS (p ≤ 0.058). Patients with LASTS co-expressing Topo2A and ERCC1 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 OS (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 (ERCC1) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).
AB - Purpose: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas (LASTS), although not standard, represents a promising option for resectable tumours. Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), HER2, excision repair cross-complementing group 1 (ERCC1) protein expression, histological response and clinical outcomes of LASTS patients. Patients and methods: A retrospective study based on clinical data and archival paraffin-embedded tumour tissue at diagnosis from 78 consecutive LASTS patients treated with neo-adjuvant chemotherapy in our institution enabled analysis of ERCC1, HER2 and Topo2A protein expression by immuno-histochemistry. Results: Disease free survival (DFS) and overall survival (OS) 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 ERCC1 status had no impact on histological response while ERCC1 positive tumours correlated with a favourable OS (p ≤ 0.058). Patients with LASTS co-expressing Topo2A and ERCC1 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 OS (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 (ERCC1) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).
KW - Adjuvant chemotherapy
KW - ERCC1
KW - Histological response
KW - Overall survival
KW - Sarcoma
KW - Topoisomerase II-alpha
UR - http://www.scopus.com/inward/record.url?scp=79957579501&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2011.02.010
DO - 10.1016/j.ejca.2011.02.010
M3 - Article
C2 - 21450455
AN - SCOPUS:79957579501
SN - 0959-8049
VL - 47
SP - 1319
EP - 1327
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 9
ER -