A study of RUNX3 protein expression and promoter methylation in different molecular phenotypes of breast cancer

Purpose To examine the RUNX3 gene promoter methylation and protein expression in 4 molecular subtypes of breast cancer. Methods The promoter methylation and protein expression of RUNX3 gene were detected in 88 breast cancers using methylation specific PCR( MSP) and immunohistochemistry method respectively. Results( 1) RUNX3 protein expression was 26. 1%,45. 0%, 76. 2% and 75. 0%,in luminal A( LA),luminal B( LB),HER-2 overexpressing( HER-2 +) and basal-like( BL) phenotype respectively,and the methylation rate was 69. 6%,85. 0%,47. 6% and 29. 2% respectively. The difference of RUNX3 expression and promoter methylation rate were significant between BL and both LA and LB tumors( P 0. 05),the significant difference of RUNX3 expression was showed between HER-2 + and both LA and LB tumors( P 0. 05),and the difference of RUNX3 methylation was significant compared with LB tumors( P 0. 05).( 2) There was statistical difference on RUNX3 methylation between RUNX3 positive and negative tumors( 36. 7% vs 82. 1%,P 0. 05).( 3) All of the 49 RUNX3 positive cases showed cytoplasm positive,no difference was found on RUNX3 protein intracellular localization between different subtypes.( 4) RUNX3 promoter methylation was correlated to clinical stage and histological grade( P 0. 05),but not correlated to lymph node metastasis,tumor size and patients' age. Conclusion Loss of RUNX3 protein expression and promoter methylation are mainly associated with ER positive breast cancers. Cytoplasm localization is common pattern of RUNX3 protein expression in breast cancer,which may related to its dysfunction. RUNX3 methylation is associated with traditional prognostic factors in breast cancer. Loss of RUNX3 protein expression and its promoter methylation may not play important roles in tumorgenesis and progression of BL.