Preliminary Exploration Of Clinical Pathological Value On HER-2 And E-cadherin In Malignant Mixed Tumor Of Salivary Gland

[PURPOSES]To investigate the potential prognostic and therapeutic target in the treatment of invasive malignant pleomorphic adenoma of salivary gland,in order to improve the survival rate and quality of life.[METHODS]Immunohistochemistry and fluorescence in situ hybridization were used for detecting HER-2 gene amplification and protein expression in pathological samples and cell lines.By targeting HER-2 in MPA cells,detection of protein expression and its downstream pathway,and changes in the proliferation and apoptosis of the corresponding cell cycle were performed via immunofluorescence,western blotting and flow cytometry.For CDH1,methylation status using bisulfite sequencing method and protein expression of pathological samples and cell lines were detected to investigate the correlation between methylation and gene expression.The application of TGF-β1 and 5-Aza-dC treatment SM-AP1 and SM-AP4 cell lines was performed to observe the influence of methylation status on the expression of E-cadherin,CDH1 gene transcription and its corresponding biological behavior influence of tumor cells.[RESULTS] 1.HER-2 amplification and over expression were found mostly in luminal subtype MPA(40.5%)instead of non-luminal subtype MPA(4.9%),and predicted a poor prognosis(P<0.001).2.HER-2 inhibitor Lapatinib could block the HER-2 downstream pathway,therefore inhibited the proliferation and enhanced cell apoptosis.3.CDH1 promoter methylation was closely associated with E-cadherin expression.Compared with non-luminal MPA,luminal MPA exhibited more E-cadherin and lower CDH1 promoter methylation rate.4.Methylation inhibitor 5-Aza-dC could restrain the methylation status of CDH1,therefore enhanced the expression of E-cadherin and inhibited the proliferation and migration of MPA cell lines.[CONSLUSIONS] 1.HER-2 overexpression or amplification is associated with MPA subtype,which predicts a poor prognosis,and could be used as a prognostic indicator.Lapatinib is consider as a potential targeted theraputic drug for MPA.2.The expression of E-cadherin is associated with MPA differentiation subtypes,and has nothing to do with prognosis.CDH1 promoter methylation is one of the important epigenetic regulation mechanism of E-cadherin silencing expression.Methylation inhibitors have potential clinical value for MPA therapy.