Change Of Expression Of Estrogen Receptor Isoforms In Different Breast Tissues And Their Significance

Breast cancer, a great harm to woman's health, is one of the most common malignant tumors in woman, and the incidence of the disease has been on rise in recent 20 yeas. Breast cancer is also one of hormone dependent malignant tumors, estrogen plays an essential role during its oncogenesis and development, mainly with estrogen receptors(ERs). Many researches have been done on the changes of ERαexpression in breast cancer, and on the relationship between ERαand prognosis of breast cancer, and a common understanding has been obtained. Many results from vitro experiments show that ERβcan repress cell proliferation and the role of transcriptional activation of ERα. Among many ERβisoforms, ERβ1/wt and ERβ2/cx proteins have been found to be expressed in breast tissues, and ERβ2 has a specific C terminal. Whereas , the changes of expressions of ERβ1 and ERβ2 in breast cancer and the relationships between ERβs and ERαare unclear so far. Whether the expressions of ERβ1 and ERβ2 and the coexpression of ERβs and ERαchange during breast cancer oncogenesis is unclear and needs further study. This study aimed to investigate the expressions of ERαERβ1 and ERβ2, and their relationship with clinicopathological parameters in normal breast tissue, benign breast diseases, breast cancer in situ and invasive breast cancer tissue , and the reasons of the changes are discussed in this study.Materials and Methods:Samples were obtained from 94 cases, including normal breast tissue, benign breast diseases, breast cancer in situ and invasive breast cancer tissue. All invasive breast caner patients did not accept any endocrine therapy or local radiotherapy. Specimens were obtained using core needle biopsy (CNB) procedures. The specimens of benign breast diseases and breast cancer in situ were obtained via surgery; normal breast tissue were adjacent normal tissues taken from fibroadenoma of breast. All specimens had been proved by pathologic examination. One part of each specimen was taken, fixed with 10% neutral formalin, embedded with paraffin, and 4μm paraffin sections were made. Immunohisto chemistry (IHC) was used to measure the expressions of ERα, ERβ1 and ERβ2 proteins with EnVisionTM system; another part was kept in liquid nitrogen as soon as possible, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expressions of ERα, ERβ1 and ERβ2 mRNA. All the results of IHC were statistically analyzed with clinicopathologic factors.Results:1. ERαwas expressed only in the breast epithelioglandulars, and mostly in the cell nucleus only. On the contrary, ERβ1 was expressed on many cell types, such as epithelioglandulars, stroma cells, myoepithelial cells, endothelial cells and lymphocytes, and expressed more in both cytoplasm and nucleus. Like ERβ1, ERβ2 was expressed in not only epithelioglandulars but also some stroma cells, lymphocytes and macrophage, and mostly in both cytoplasm and nucleus.2. Compared with normal tissue and benign diseases , ERαprotein and mRNA level were down-regulated in invasive cancer significantly (P<0.01); in cancer in situ ERαprotein(P <0.01)and mRNA(P <0.05)were down-regulated significantly.3. Compared with normal tissue and benign diseases, ERβprotein (P<0.01) and mRNA(P <0.05)level were down-regulated in invasive cancer noticeably.4. There was no significantly difference in the expression of ERβ2 protein and mRNA in normal tissue , benign diseases, cancer in situ, and invasive cancer (P﹥0.05).5. Compared with normal tissue and benign diseases , coexpression of ERαand ERβ1, and ERαand ERβ2 protein decreased in cancer in situ and invasive cancer remarkably (P<0.01).6. In invasive breast cancers which ERβ2 positive, positive rate of immunohis- tochemistry staining of P53 protein increased markedly (P <0.05).Conclusion:1. ERβ1 and ERβ2 expressed widely in stroma cells might be related to the modulating role of the breast tissue, but this still need to be studied.2. ERαexpression in invasive breast cancer and breast cancer in situ is down-regulated, and transcripton and translation levels change. This may be due to normal structure loss during atypical hyperplasia[1]. 3. ERβexpression in invasive breast cancer is down-regulated, and transcripton and translation levels change. there is a difference in the changes of expressions of ERβ1 and ERβ2 protein and mRNA during breast caner oncogenesis; coexpressions of ERα, ERβ1 and ERα, ERβ2 in invasive breast cancer are down-regulated, These changes may be correlated to breast cancer oncogenesis, but its mechanism is not known yet.4. In invasive breast cancers which ERβ2 positive, the positive rate of P53 protein is increased remarkably, which may be correlated to the dysregulation of tumor cell apoptosis.