Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma
1 Aix Marseille Univ, CRO2, 13284 Marseille, France
2 INSERM, U911, 13005 Marseille, France
3 APHM, Timone Hospital, Department of Medicine, Division of adult oncology, 13005 Marseille, France
4 Integrated Center for Oncology, Biostatistics Unit, Nantes, France
5 APHM, Timone Hospital, Department of Pathology, 13005 Marseille, France
6 Integrated Centre of Oncology, Department of Biology, Nantes, France
7 INSERM U892, IRT-UN, Nantes, France
8 APHM, Timone Hospital, Department of Medicine, Division of Pediatric Oncology, 13005 Marseille, France
BMC Cancer 2014, 14:606 doi:10.1186/1471-2407-14-606Published: 20 August 2014
The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as “poor responders” (PR) and “good responders” (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment.
Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort.
ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy.
Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.