Expression And Clinical Significance Of HMAM-mRNA And Survivin Protein In Breast Cancer Patient And The Study Of Their Correlation

ObjectiveBreast cancer is high incidence malignant tumors of women, which incidence rate showed an increasing trend [1]. The treatment of breast cancer are more, but the prognosis is not very satisfactory; The main factors of it are local recurrence and distant metastasis, which is difficult to get a diagnosis timely [2] At present, breast cancer has been recognized as a systemic disease. One of the main reasons of postoperative local recurrence or metastasis is not detected the micrometastases preoperatively or cancer cells sliping into the blood among the operation. With the development of imaging mammography as the main means of check, especially accompanied by breast MRI becoming more sophisticated, the detection rate of breast cancer before surgery is increasingly high. So, to look for a specific marker signing of breast cancer and its early metastasis has a very important clinical value detection of micrometastasis at a sub-clinical stage of cancer.Mammaglobin gene (humanmammaglobin.hMAM) is a tissue-specific gene which was amplified by the American scholar,located in chromosome11q12-13, a member of the globin gene family, which compiled the glycoprotein contains23amino acids.Typically, hMAM gives a low expression in normal breast epithelial cells, but a higher expression in breast cancer cells, and it concerns with breast cancer histology,tumor stage or hormone receptor status. It proves that hMAMmRNA gives a low level of expression in normal mammary epithelial cells, does not express in normal blood and bone marrow, and are upregulated in breast cancer and tend to be higher. hMAMmRNA is one of the judgment and monitoring of breast cancer and blood micro-metastasis of the most important markers.Survivin is a apoptosis suppressor gene discovered, a new member of inhibitor of a poptosis family, which has a powerful inhibitor of a poptosis functions. Survivin protein is an inhibitor of a poptosis protein, involved in the regulation of cell division. It is to control the cycle of apoptosis checkpoint, and it was recently discovered closely to link with tumor angiogenesis. And the expression of Survivin protein seems to be a specific tumor, depth of tumor invasion, lymph node metastasis, TNM stage, vascular invasion or overall survival and other potentially relevant. Some recent data indicate that some early local recurrence or distant metastasis or poor prognosis of breast cancer tissue give a high expression of Survivin protein.The study aimed to observing the dynamic expression of hMAM mRNA in the peripheral blood of breast cancer by nested N-RT-PCR and detecting expression of survivin protein in breast cancer tissue byimmunohistochemistry S-P (streptomycin avidin. peroxidase).To analyze the expression of hMAMmRNA and Survivin protein and the correlation with clinical pathology factors, such as TNM stage, lymph node metastasis, Her-2and the correlation with breast cancer prognosis, and to Provide a theoretical basis for the diagnosis and prognosis of breast cancer patient. At the same time, to research and analyze function of hMAMmRNA in breast cancer blood micro-metastasis, and to explore the impact of postoperative adjuvant chemotherapy for the control of breast cancer blood micro-metastases.Methods70cases of breast cancer with pathologically confirmed were collected as the experimental group, from breast surgery of First Affiliated Hospital of ZhengZhou University between Sep2009and Sep2010;70cases of benign breast tumor with pathologically confirmed were collected as the experimental group, from breast surgery of First Affiliated Hospital of ZhengZhou University between Sep2009and Sep2010as control group. Experimental group and control group were completely female which between the ages of32-70(average58.36±8.97). By N-RT-PCR to detect hMAMmRNA in the peripheral blood of experimental group and control group; By N-RT-PCR, the experimental group70cases of breast cancer patient were detected hMAMmRNA in the peripheral blood preoperatively,and detection of peripheral blood hMAMmRNA expression after receiving three cycles of postope-rative adjuvant chemotherapy, once again detect the expression of hMAMmRNA in peripheral blood of patient; All70cases of breast cancer patient with postoperative tissue were detected the expression of Survivin by immunohistoch emistry chemical S-P (streptomycin avidin peroxidase); Combined with preoperative patient history, physical examination, laboratory examinations, intraoperative findings, postoperative routine pathology results,to analyse the relationship of hMAMmRNA, Survivin and axillary lymph node metastasis, tumor size. TNM stage, patient age, menopausal status.and5-year survival, as well as the correlation between Survivin and hMAMmRNA. All statistical calculations were carried out using the statistical software named Statistical Product and Services Solutions (SPSS)17.0.ResultsThe hMAMmRNA microprobe analysis byN-RT-PCR technique,70cases of breast cancer patient in the peripheral blood sPecimens,58cases of201bp specific amPlified bands, the positive expression rate of58/70(82.86%); and70casesone cases of breast fibroadenoma patient201bp sPecific amplification bands only in the peripheral blood of the control group, the Positive expression rate of1/70(1.41%)70cases of expression hMAMmRNA in the peripheral blood of breast cancer patient connected with axillary lymph node status, clinical TNM stage,and as lymPh node metastasis the expression rate of hMAMmRNA increased (X2=7.261, P=0.021).Ⅰ, Ⅱ, Ⅲ and IV of breast cancer patient hMAM mRNA positive expression rates were12.1%,29.3%,57.6%and82.3%. No connection with age, menopausal situation, age of onset, tumor size (divided into T≤2cm and T>2cm two groups) histological tyPe, Ki67, P53and ER, PR; Her-2(P>0.05)Among70cases of breast cancer patient,58cases of peripheral blood hMAMmRNA positive breast cancer tissue of patient with Survivin staining was positive in47cases.12cases of hMAM mRNA-negative patient with breast cancer organization Survivin staining was positive in3cases. hMAMmRNA in peripheral blood had correlation with Survivin in breast cancer tissue (X2=7.113, P=0.014)58cases hMAMmRNA positive patient were detected before adjuvant chemotherapy. After three cycles chemotherapy,41cases hMAMmRNA positive patient became negative,70.69%(13/17).12cases hMAMmRNA expressed negative patient became no positive after chemotherapy, suggesting that adjuvant chemotherapy can reduce the blood hMAMmRNA positive rate. There was significant difference before and after chemotheraPy (P=0.001)70cases of invasive breast cancer tissue, Survivin expressed53cases of positive staining, the positive rate of75.71%(53/70).25cases of breast fibroadenoma’s Survivin positive rate was28.0%(7/25),which significantly less than the expression of Survivin in breast cancer tissue. The X2test confirmed statistically significant (X2=10.324, P=0.006)Expression level of survivin in breast cancer had no correlaion with age, the age of onset, tumor size (divided into T≤2cm and>2cm two groups), pathological type, Ki67, P53, and ER, PR, Her-2(P>0.05), but axillary lymph node metastases and tumor TNM stage. Survivin in the Positive rate of lymph node metastasis was89.12%(45/51), were significantly higher than the21.53%(4/19) without lymph node metastasis,and thy were significant difference (P＜0.05). Accompanied by lymph node metastasis,Survivin positive expression rate increase (x2=8.227, P=0.017). II, III, IV of Survivin expression rate of breast cancer patient were42.3%,69.8%and85.3%, and III, IV Survivin positive expression rate was higher than I, II (x2=6.723, P=0.010).Regarding Survivin positive expression rate, there were significant differences between early breast cancer patient with advanced breast cancer Patient (p＜0.05)Conclusions hMAMmRNA can be as one of particular markers of hematogenous micrometastasis in breast cancer micrometastases; Survivin protein can be used as an important indicator to determine breast cancer treatment; The expression of hMAMmRNA is relevant with Survivin protein’s expression, and, they promote tumor angiogenesis and hematogenous micrometastasis together,;thy can be used as a reference to judge the prognosis of breast cancer together; hMAMmRNA is an important indicator to determine the efficacy of breast cancer after chemotherapy dynamicly.