Correlation Between Gene Amplification Of ErbB Receptor Family And Clinicobiological Behaviors Of Osteosarcoma

Background: Osteosarcoma is a malignant bone tumor with extremely high invasion,metastasis and mortality.The prognosis of patients with osteosarcoma remains poor.The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis.However,the role of ErbB receptor family in osteosarcoma has not been fully understood.The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma.Methods: Fluorescence in situ hybridization(FISH),Reverse transcription real-time quantitative PCR and Western blot(WB)were used to detect the gene,m RNA and protein expression of ErbB receptors in 60 primary osteosarcoma specimens and 30non-neoplastic bone tissues.Results: FISH analyses showed that 17(28.33%),15(25.00%)and 15(25.00%)osteosarcoma specimens presented with amplification of EGFR,ErbB3 and ErbB4 gene,respectively,which were significantly higher compared with non-neoplastic bone tissues.The RT-q PCR and WB analyses further verified the m RNA and protein expression levels of EGFR,ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues.The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advance surgical stage.The amplification of EGFR,ErbB3,ErbB4 and the co-amplification of EGFR-ErbB3,EGFR-ErbB4,ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis.In addition,the amplification of EGFR,ErbB3,ErbB4 in osteosarcoma and the co-amplification of EGFR-ErbB3,EGFR-ErbB4,ErbB3-ErbB4 were significantly associated with the poor prognosis of patients.Conclusion: The amplification of EGFR,ErbB3 and ErbB4,as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapy targets for osteosarcoma patients in the future.