title: Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma.
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.
authors.affiliation: Aix Marseille Univ, CRO2, 13284 Marseille, France. sebastien.salas@ap-hm.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Salas
authors.forename: Carine
authors.initials: C
authors.lastname: Jiguet-Jiglaire
authors.forename: Loic
authors.initials: L
authors.lastname: Campion
authors.forename: Catherine
authors.initials: C
authors.lastname: Bartoli
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frassineti
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Deville
authors.forename: André
authors.initials: A
authors.lastname: Maues De Paula
authors.forename: Fabien
authors.initials: F
authors.lastname: Forest
authors.forename: Pascal
authors.initials: P
authors.lastname: Jézéquel
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Corinne
authors.initials: C
authors.lastname: Bouvier
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics*; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D048052:Mitogen-Activated Protein Kinase 3