On breast cancer in ER PR and HER expression and its significance（在乳腺癌ER公关和HER的表达及其意义）

1、 On breast cancer in ER PR and HER2 expression and its significance Abstract Objective To investigate HER2, ER, PR protein region in the north, the expression of breast cancer patients, and HER2 and ER, PR expression between the correlation method of the north, areas of breast cancer surgical specim

2、ens were 10% neutral formalin-fixed, two-step method using SP combined immune staining results of HER2 protein expression was negatively correlated with ER and PR expression also showed a negative correlation. Keywords ER PR HER2 breast cancer Breast cancer is harmful to womens health first, the inc

3、idence rate showed a gradual upward trend. Breast cancer is a systemic disease, the exact cause has not yet fully understood. Tumor invasion and metastasis is a multi-gene regulation, multi-step, multi- stage of evolution, which is the abnormal proliferation of tumor cells in tumor invasion and meta

4、stasis based on changes in adhesion and enhanced exercise capacity, and loss of contact inhibition is the extracellular conditions of invasion and metastasis in breast cancer-related proteins associated with prognosis and treatment mainly for ER, PR and HER2, understanding the expression of these th

5、ree proteins is the key to breast cancer treatment. 1 Materials and methods 1.1 Research material collected in January 2006 - December 2009 Peoples Hospital during the Beiliu pathological diagnosis of breast cancer surgical specimens of 84 cases, 37-year-old minimum age, maximum 71 years, mean age 5

6、1 years, median age 53 years All specimens were 10% neutral formalin-fixed, paraffin-embedded sections, all specimens were re-production and re-read the piece in order to further clarify the diagnosis. 1.2 Research Methods All immunohistochemistry reagents were purchased from Fujian step the new com

7、pany, ready to use. Two-step method using SP immunohistochemical staining, concentrated DAB chromogenic kit, steps in accordance with instructions. 1.3 Detection After all specimens were fixed in 10% neutral formalin, conventional dehydrated, embedded in paraffin, sliced ?thickness of 4m, using conv

8、entional immunohistochemistry SP staining method specific method is as follows: All slides were confirmed by APES-treated film, 4m serial sections, dewaxing to hydration, 3% hydrogen peroxide at room temperature for 10 minutes to block endogenous peroxidase activation, soaked in distilled water for

9、2 minutes, microwave repair of high fire for 15 minutes, drops plus an anti, 4 refrigerator overnight, PBS wash 5 minutes * 3, dropping A reagent at room temperature for 30 minutes, PBS washed 3 minutes * 3, dropping solution B, incubated at room temperature 20 minutes, PBS washed 3 minutes * 3, DAB

10、 solution, the color, tap water to terminate color, hematoxylin-stained nuclei, dehydrated, and transparent, were mounted. With known positive film as a positive control to 0.01mol / L phosphate buffered saline (PBS instead of primary antibody as negative control. 1.4 The results to determine the ce

11、ll-free coloring of (-, light yellow or 25% positive cells for the (+, yellow or brown positive cells in 25% -50% for the (2 +, tan, or the number of positive cells> 50% is (3 +, each slice randomly selected 10 high-power fields, each field observation of 100 tumor cells, calculate the average pe

12、rcentage of positive cells in the percentage of positive cells for the tumor in which the interpretation of HER2 reference 2007 CAP / ASCO criteria, that any proportion of invasive cancer cells with weak, incomplete capsule stain (1 +),>= 10% of invasive cancer cells showed an uneven or weak but

13、significant staining or membrane surrounding the distribution of 30% invasive cancer cells show strong, complete capsule color is (2 +,> 30% of invasive cancer cells showed homogeneous, strong coloring of the envelope (3 +. ER, PR coloring parts of cancer cells the nucleus. 2 results HER2 and ER,

14、 PR expression in breast cancer in the table below As shown above, this paper 84 cases of breast cancer patients, HER2 and ER, PR expression was negatively correlated, and its expression were significantly statistically significant (P <0.01. 3 Discussion Breast cancer is a common malignancy of wo

15、men, the incidence rate showed an increasing trend, according to World Health Organization, the International Cancer Center, the latest statistics show that about 1.2 million worldwide each year with breast cancer. Breast is a sex hormone dependent organs, their growth and development of value-added

16、 and cells are subject to estrogen and progesterone effects 1. HER2 (human epithelial growth fator receptor-2, HER2, including a variety of epithelial origin, including breast cancer overexpressed in tumors 2, and tumor occurrence, development, transfer and decreased sensitivity to chemotherapy and

17、close, is a very promising target for gene therapy 1. Links to free download HER2 is a growth factor receptor family member, is located on chromosome 17q21, a molecular weight of 185KD transmembrane protein encoded by the intracellular tyrosine kinase domain, cross- membrane area and the extracellul

18、ar domain composed of three parts, is a transmembrane protein tyrosine kinase activity of protein, epidermal factor receptor family members belonging to 3 and so far has not found a direct combination with the HER2 ligand, with other receptor heterodimers into play after the signal transduction, com

19、pared with non-HER2 dimer a stronger signal. HER2 receptor cells district PTK activity itself also has a number of tyrosine residues phosphorylation sites. HER2 protein can promote DNA synthesis, cell division, increased secretion of proteolytic enzymes, growth of cancer cells to speed up, increase

20、exercise capacity, enhanced tumor invasion and metastasis, the degree of malignancy increased 4. Hussein et al 5 found that HER2 proto-oncogene expression in breast cancer 10-34%, its expression and poor prognosis. HER2 expression in this study was 20.24% (2 + or more were judged to be positive, mor

21、e consistent with the relevant reports , but patients also need 2 + detected by FISH to determine HER2 gene amplification. and the research group of HER2 protein expression and ER, PR expression was negatively correlated, indicating that the gene activation in the ER, PR is more common in hard tumor

22、s. Breast cancer patients after CMF chemotherapy for classical program (cyclophosphamide, methotrexate, fluorouracil and CMF scheme (cyclophosphamide, doxorubicin, fluorouracil, respectively, typical of alkylating agent and anthracycline , mainly through the signal conditioning and control of cell c

23、ycle and inhibition of tumor cells, but HER2 overexpression increased cell hyperplasia, the cells quickly from the cytotoxicity of chemotherapeutic drugs to recover, causing drug resistance. Herceptin (Trastuzumab is a kinds of new high efficiency, low toxicity, highly selective targeted therapy dru

24、gs, over-expression of HER2 breast cancer can overcome chemotherapy, radiotherapy, endocrine therapy resistance, increase the efficacy of the latter. Herceptin is not only adverse reactions, and for in combination with other chemotherapy drugs for patients with HER2-overexpressing breast cancer prov

25、ides a new therapeutic approach has brought new hope. Breast tissue in the presence of estrogen and progesterone (ER, PR expression, transcripts for the hormonal regulation, cytokine-mediated responses in breast cancer cells retained on the ER, PR expression. ER protein deposition by a factor of 2 4

26、S, molecular mass of 65000 hormone binding protein molecules form dimers, PR is the end product of estrogen action, PR estrogen synthesis must have as a start, that the presence of ER and PR does a dynamic 6. estrogen to its receptor, can promote the synthesis of new proteins, including progesterone

27、 receptor synthesis, both regulating breast cell growth, differentiation, when the cancerous mammary epithelial cells, ER, PR will be some or all of the missing. Studies have shown that breast cancer cells of ER, PR mRNA levels decreased. It is reported that estrogen and progesterone receptor expres

28、sion and HER2 protein expression was negatively correlated, in this study, the same result has also been there Studies have shown a high degree of breast cancer cells, low degree of malignancy, the ER, PR expression rate, endocrine treatment and prognosis. Chu et al 7 studies have shown that in brea

29、st cancer cells, ER, PR positive rate of about 50-70%, in this study of ER, PR expression were 73.81% and 71.43%, consistent with the literature. ER, PR-positive breast cancer patients for endocrine drugs tamoxifen (tamoxifen, TAM sensitivity higher individual ER-positive breast cancer response to e

30、ndocrine therapy, 55%, while the ER, PR positive, compared with 75% while 80%, and negative for endocrine therapy are less sensitive. So ER, PR has become the observed detection breast cancer treatment and prognosis of. The incidence of malignant tumors with a variety of genes related to the change,

31、 multi-gene hypothesis in a synergistic constant attention, that the incidence of cancer, all stages of development and transfer, at least two or more different functions of their abnormal activation of genes play a different role, and in time and space co-ordination, synergy to promote cancer. ER,

32、PR is a specific function of proteins, detection of their prognosis, guiding endocrine treatment has some significance. research has shown, ER , PR positive breast cancer after 5-year survival rate was significantly higher than ER, PR-negative breast cancer, and less recurrence and distant metastasi

33、s 8. HER2 is and tumor growth, invasion and metastasis of important molecules, molecules to target HER2 gene therapy, can also inhibit the malignant phenotype of various tumors, especially breast cancer with HER2 overexpression, and thus the effective tumor the control with the development of medica

34、l science and molecular studies of the HER2 protein and in-depth, HER2 overexpressing breast cancer chemotherapy program with the choice of endocrine therapy and targeted therapy will be a thorough understanding of the relevance, so as to effectively control breast cancer, HER2-positive breast cancer in particular provide new ideas and methods. References 1 Liu Yao, Liu Chao, Tao Yurong. Her2 overexpressing breast cancer treatment and related research J. Modern Oncology, 2010 (1:182-184. 2 HARARI D, YARDEN Y. Molecular mechanisms unde