| Objective:To detecte the different expression of thyroid hormone receptor (31 (TRβ1) in the normal tissues and breast carcinoma, then investigating methylation status of CpG island in the promoter region of TRβ1 to explore the relationship between them. Meanwhile, combined with clinicopalhologic features, for example menopause, lymph node metastasis and histological type, to analyze methylation status and biological behaviour in breast cancer.Methods:Using reverse transcriptaseepolymerase chain reaction (RT-PCR) technique,40 cases the breast carcinoma and 10 cases the normal tissues were detected for their expression of the TRβ1 mRNA. Meanwhile, Methylation-specific polymerase chain reaction (MSP) combined with direct sequencing was used to detecte the methylation status of CpG island in the promoter region of TRβ1 in 10 cases the normal tissues,40 cases breast cancer tissues and corresponding paraneoplastic samples which is 5cm part from breast carcinoma.Results:1. The aberrant expression of TRβ1 was 85%(34 cases) out of 40 cases breast cancer samples, including reduction in 20 cases and deletion in 14 cases samples. Only 6 cases tissues was normal expressed (15%). Accordingly, mRNA of 10 cases normal breast tissues were all expressed. The expression of TRβ1 mRNA in breast carcinoma was lower than that in the normal tissues (χ2=22.800, P<0.01). At the same time, the OD value was 0.3076±0.4194 in the 40 breast cancer samples which was lower than that in normal tissues (t=-28.512, P<0.01).2. The frequency of methylation in the promoter region of CpG island of TRβ1 in breast cancer samples and paraneoplastic tissues respectively were 80.0%(32/40) and 72.5%(29/40) while there were no significant between two groups (χ2=0.621, P> 0.05). By contrast, only 10% in the normal tissues which was significantly lower than in breast cancer samples(χ2=14.489, P<0.01)and in paraneoplastic tissues(χ2=10.547, P<0.01). Meanwhile direct sequencing showed aberrant methylation of TRβ1 promoter in three CG site at least. The frequency of methylation was more than 30% But no significant association of abnormal methylation was identified with clinicopalhologic features.3. Methylation in the promoter region of CpG island of TRβ1 was found 31 cases out of the 34 cases breast cancer patients in whom TRβ1 mRNA expression was reduced, but only one case methylation was found the six cases in whom TRβ1 mRNA expression was normal. There was a significant correlation between them (r=-0.415, P=0.015). The expression level of TRβ1 mRNA in which TRβ1 promoter methylation (0.170±0.036)was significant lower than that with unmethylation in the promoter region of CpG island of TRβ1(0.343±0.050), revealing a significant difference between TRβ1 methylation status and mRNA expression (t=13.842, P<0.01). There was a strong correlation between the expression levels and methylation status of CpG island in the promoter region of TRβ1.Conclusion:1. The expression of TRβ1 mRNA in breast carcinoma was lower than that in the normal tissues, revealing the aberrant expression of TRβ1 mRNA playes a role in the development of the breast cancer.2. The high methylation of the promoter region of CpG island of TRβ1 in breast cancer and corresponding paraneoplastic samples was one of the mechanism of aberrant expression of TRβ1 mRNA.3. There is no significant association between TRβ1 methylation status and clinicopalhologic features, for example the menopause, lymph node metastasis and histological type. This observation suggests that TRβ1 methylation in breast cancer occurs in a carcinogenic pathway-dependent, rather than a progression-dependent manner.
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