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Open Access Highly Accessed Research article

Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma

Sébastien Salas123*, Carine Jiguet-Jiglaire12, Loic Campion4, Catherine Bartoli12, Frédéric Frassineti12, Jean-Laurent Deville123, André Maues De Paula5, Fabien Forest5, Pascal Jézéquel67, Jean-Claude Gentet8 and Corinne Bouvier125

Author Affiliations

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

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BMC Cancer 2014, 14:606  doi:10.1186/1471-2407-14-606

Published: 20 August 2014

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords:
Conventional osteosarcomas; Predictive factors; Chemotherapy response; STAT3; ERK1