| [Objective] To detect the methylation status of estrogen receptor beta (ERβ) promotor and its protein expression in intraductal proliferative lesions, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia(ADH) and ductal carcinoma in situ(DCIS) of breast, as well as invasive breast carcinoma. At the same time we investigated the possible correlation between the expression of ERβ protein and methylation status of ERβ gene. The aim of this study is to understand what role of the ERβ plays in the breast cancer genesis, and to find more useful information for endocrine therapy of breast cancer.[Methods] Forty-four cases of intraductal proliferative lesions of breast (including twelve UDH, eight ADH and twenty-four DCIS cases) and fourteen cases of invasive breast carcinoma were collected from Qi Lu Hospital of Shandong University from 2002-2005, as well as six normal breast tissue from plastic operation. The samples were fixed in 10% formalin and paraffin embedded. All archival haematoxylin and eosin-stained sections were reviewed to confirm the diagnosis. The CpG island methylation of ERβ promoter was detected using methylation-specific polymerase chain reaction (MSP) on all cases. And immunohistochemistry was used to determine the expression of ERβ protein on fifty-seven cases of them. All data were analyzed by the SPSS12.0 software for windows.[Results] The CpG island methylation of ERβ promoter were detected in senven of twelve (58.3%) in UDH samples, five of eight (62.5%) in ADH samples, fifteen of twenty-four (62.5%) in DCIS samples and eleven of fourteen (78.6%) in IBC samples. By contrast, the methylation of ERβ gene in normal breast tissue was absent. The rate of methylation was increasing from normal breast tissue to UDH to ADH to DCIS and to IBC. However, a decreased expression of ERβ protein was observed in the process from normal breast tissue to intraductal proliferation and to invasive breast carcinoma. The ERβ protein positive cases were nine of eleven in UDH, three of seven in ADH, ten of twenty-two in DCIS, and three of eleven in IBC. All normal mammary cases were ERβ positive. The rate of ERβ positive cells was 86.4% in normal mammary gland, 64.3% in UDH, 25.0% in ADH, 27.2% in DCIS, and was 9.3% in IBC. The negative correlation was observed between the ERβ protein expression and the methylation of ERβ promoter (P<0.01). Furthermore, no correlation was found between ERβ and ERa, both in methylation status and protein expression, binding the data we obtained before.[Conclusion] There is CpG hypermethylation of ERβ promoter in breast intraductal proliferative lesions as well as in invasive breast cancer, while there is no methylation in normal breast tissure. The ERβ gene hypermethylation is already existed in premaligment lesions. Although the methylation rate in UDH is lower than in ADH or DCIS or IBC, there is no significant difference between them. The methylation rate trends to increase from UDH to ADH to DCIS and to IBC. While the expression of ERβ protein is decreased in the process from normal mammary gland to intraductal proliferation, and to invasive breast carcinoma. The hypermethylation of ERβ promoter region may be an important mechanism for the decreased expression of ERβ protein. Since ERβ is unrelated with ERa, both in methlation status and protein expression, it may play a different role in endocrine therapy of breast carcinoma.
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