| Breast cancer is the most common female malignant tumor which endangers the life and health of the female. It is about 7%-10% out of all malignant tumors in China. The incidence of the breast cancer is higher year by year. It is changing from the surgery to combined therapy along with we know more about the biology feature of the breast cancer. Now the therapy for the breast cancer includes operation, chemotherapy, radiotherapy, endocrine therapy, molecular targeted therapy and so on. With the using of the new medicine of endocrine therapy, the curative effect is more and more significant through the control of sex steroid level in both circulation and local tissue. And now the endocrine therapy for breast cancer has a more important role in the breast cancer combined therapy. Recently more and more scientists focus on the intracrinology of breast cancer, and the role of the local synthesis of the sex steroid in the endocrine target tissue becomes more important. Otherwise the function of the androgen in breast cancer is still controversial. Androgen therapy has been reported to have response rates of up to 46% in ER-positive patients. About 30% of breast cancer is ER or PR negative, and AR was found in about 49% of them. There is no effective endocrine therapy for them at present, so the using of androgen for them maybe become a method of endocrine therapy. Through the studying of the expression of 17β-hydroxysteroid dehydrogenase type 2 and type 5 in breast cancer and adjacent non-malignant tissue, and the correlations between the results and the clinical factors, we want to analyze the strength of the expression of 17β-HSD 2, 5 and the role of the two enzymes in the metabolism of sex steroid. We also analyze the relationship among the sex steroids by studying the correlation among the sex steroid receptors.Prepare the protein of type2 and type5 17β-HSD, injected sc with 1ml at multiple sites of New-Zealand rabbits. Collect the antiserum of the rabbits and purify it. Positive antiserum was analyzed by immunoblot. The expression of 17β- HSD2, 5 and CDC-47,ERα,ERβ,PRA,PRB,AR in 50 specimens of female human breast carcinoma and adjacent non-malignant tissues were studied by immunocytochemistry. These results were correlated with the clinical parameters.Results: 1,17β-HSD2 was found in the cytoplasm but not nucleus of tumor cells in 10% of cases and the stain was very weak. In adjacent non-malignant tissues, 92% of cases were positive and the enzyme was detected in the cytoplasm of epithelial cells of the acini and ducts. There was also no stain found in the nucleus, and the stain was mainly in the outer layer of the acini. The vessel wall was stained both in breast cancer tissue and adjacent non-malignant tissue. 17β-HSD5 was found in the cytoplasm of tumor cells in 44% of cases. In adjacent non-malignant tissues, 74% of cases were positive and the enzyme was detected in the cytoplasm of epithelial cells of the acini and ducts. No matter 17β-HSD2 or 17β-HSD5, there was no stain found in the nucleus and occasionally we found the stroma cell was positive. The control group was negative.There was a significant difference between the malignant tissue and the adjacent non-malignant tissues in the percentage of positive cells in both enzyme(x2=41.0000,P<.0001; x2=7.7586,P=0.0053). 2,All kinds of the receptors were found in the nuclei of tumor cells and epithelial cells of the acini and ducts except PRA and PRB. They also expressed in the cytoplasma and the stain was weak. The reason was not clear now. The percentage of the positive cells are 98%,74%,100%,42%,42%,84% in the malignant tissue and 48%,94%,100%,52%,36%,94% in the adjacent non-malignant tissues respectively. There was a significant difference between the malignant tissue and the adjacent non-malignant tissues in the percentage of positive cells in CDC-47 and ERα.(χ2= 25.0000, P<.0001;χ2= 8.3333, P=0.0039). 3,In malignant tissue, the expression of 17β-HSD2 was significantly correlated with the expression of 17β-HSD5 in adjacent non-malignant tissues (r=-0.29624,P=0.0367), the expression of PRA in adjacent non-malignant tissues(X2=5.1282,P=0.0235) and the menopause(X2=4.9257,P=0.0265). In adjacent non-malignant tissues, the expression of 17β-HSD2 was significantly correlated with the stage of the breast cancer (r=-0.28745 ,P=0.0430)and the expression of the CDC-47 in the adjacent non-malignant tissues(r=0.28873,P=0.0420). In adjacent non-malignant tissues, the expression of 17β-HSD5 was significantly correlated with the age of patients(r=0.34763,P=0.0134), menopause(r=0.39859,P=0.0046), the expression of ERβ(r=-0.31095,P=0.0280)in malignant tissue, the expression of PRA (X2=7.4871,P=0.0062)and ERα(X2=9.0835,P=0.0026) in adjacent non-malignant tissues. 4,In malignant tissue: the expression of AR was significantly correlated with the expression of ERα(r=0.28424,P=0.0454), the expression of PRA and PRB were significantly correlated with the expression of CDC-47(r=-0.42281,P=0.0025,r=-0.52952,P=<.0001), the expression of ERαwas significantly correlated with the expression of PRA , PRB and CDC-47(r=0.40318,P=0.0041; r=0.37860,P=0.0067; r=-0.46091,P=0.0008). In adjacent non-malignant tissues: the expression of PRA was significantly correlated with the age of patient(r=-0.31681,P=0.0282), the expression of ERβwas significantly correlated with the expression of CDC-47(r=0.39960,P=0.0044). No matter in malignant tissue or in adjacent non-malignant tissues the expression of PRA was significantly correlated with the expression of PRB (r=0.84010,P=<.0001,r=0.42457,P=0.0026). Conclusion: 1,In adjacent non-malignant tissues the expression of 17β-HSD5 was significantly higher than in cancer tissue, moreover AR was the same as 17β-HSD5. It indicated the important role of 17β-HSD5 in the development and/or progression of breast cancer, and it also suggested the androgen may suppress the breast cancer proliferation through AR.2,The expression of 17β-HSD5 of menopause women was significantly higher than premenopause ones in adjacent non-malignant tissues, this indicated the changing of the androgen local synthesized in the menopause women. 3,17β-HSD5 was able to regulate the metabolism of the progestogen by it's 20a-HSD activity. 4,The significantly different expression of 17β-HSD 2 between the cancer tissue and the adjacent non-malignant tissues indicated it's protective function in breast tissue. As the expression of 17β-HSD 2 in adjacent non-malignant tissues was significantly correlated with tumor stage, it indicated 17β-HSD 2 play an important role in the development and/or progression of breast cancer.5,because the tumor cells expressing ERαhad lower proliferative activity, ERαwas a good prognostic indicator. |
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