EXPRESSION OF E-CADHERIN/CATENIN COMPLEX IN BREAST CANCER

Objective： To detect the expressions of E-cadherin, α-catenin and β-catenin and analyze the relationship between Ecadherin-catenin adhesion complex and clinicopathological features in breast cancer. Methods： The expressions of E-cadherin, α-cadherin and β-catenin in specimens of 54 breast cancer, 21 normal breast tissues around tumor, 15 breast hyperplasia of usual type and 15 breast atypical hyperplasia were detected by immunohistochemical method. Results： In 21 normal breast tissues, E-cadherin and α-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The staining character of the three proteins in breast hyperplasia of usual type was the same as that in normal breast tissue. In breast atypical hyperplasia, the abnormal expression rates of E-cadherin, α-catenin and β-catenin were 6.7%, 13.3% and 26.7%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 33.3%. In breast cancer, the abnormal expression rates of E-cadherin, α＋catenin and β-catenin were 51.9%, 63.0% and 61.1%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 88.9%. Abnormal expression of E-cadherin and α-catenin were significantly correlated with histological grade. Abnormal expressions of α-catenin and β-catenin were significantly correlated with TNM staging, axillary lymph nodes metastasis and postoperative distant metastasis. Abnormal expression of E-cadherin-catenin complex was correlated with TNM staging, histological grade and axillary lymph nodes. Abnormal expression of β-catenin was negatively correlated with expression of HER-2. COX multiple factor analysis showed that E-cadherin or α-catenin or β-catenin was not independent prognostic indicator. Conclusion： Abnormal expressions of E-cadherin, α-catenin and β-catenin frequently occur in breast cancer. Abnormal expression of E-cadherin-catenin complex is correlated with differentiation disturbance and metastasis. Combined measurement of E-caherin, α-catenin and β-catenin may improve accuracy and sensitivity of predicting metastasis and prognosis of breast cancer.     

Pin1、β-连接素和细胞周期素D1在老年肺癌组织中的表达及临床意义

Objective:To investigate the expressions and correlations of Pin1,β-catenin and cyclin D1 in elderly lung carcinomas.Methods:The expressions of Pin1,β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors.Results:(1) The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 (50%)cases and 60 (65.22%) cases respectively and 56 (60.82%) cases showed positive immunoreactivity for β-catenin in the nuclear and (or) cytoplasmic fraction in tumor tissues,In normal tissue,the expressions of Pin1 and cyclin D1 were negative,the expression of β-catenin was lied in cell membrane.(2) In lung carcinomas the expressions of Pin1,β-catenin and cyclin D1 correlated with tumor differentiation (P＜0.05).The pesitive expression rate and intensity of Pin1 correlated with tumor stage (P=0.032) and lymph node positive disease (P=0.041).The expression of β-catenin correlated with lymph node positive disease (P=0.012).(3) High expression levels of Pin1 correlated with aberrant β-catenin expression (P=0.000) but did not show a correlation with cyclin D1 (P=0.157).Conclusion:In elderly lung carcinomas,the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene,however,this target gene was not cyclin DI.The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.     

Expression and clinical significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions简

Objective： The aim of our study was to observe the expressions and clinical Significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： Immunhistochemical UltraSensitiveTM S-P method was employed to detect the expression of E-cadherin, β-catenin and E-cadherin-catenins complex in 128 cases of invasive ductal carcinomas, 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia, 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The express of E-cadherin, β-catenin and their relationship with mult biological parameters including histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： （1） The staining patterns character of E-cadherin, β-catenin and E-cadherin-catenins complex： In UDH breast tissues, E-cadherin and a-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The abnormal expression of the three proteins occurred in breast invasive ductal carcinomas, ductal carcinoma in situ and atypical ductal hyperplasia tissues, showing cytoplasmic or nuclear staining, decrease and loss of cytomembrane staining. （2） The abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex in invasive ductal carcinomas were 53.91%, 65.63% and 81.25%, which were significantly higher than that in ductal carcinoma in situ, atypical ductal hyperplasia, usual ductal hyperplasia tissues （P 〈 0.01）. Compared with usual ductal hyperplasia breast tissues group, the abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex were significantly decreased （P 〈 0.01） in the breast cancer group. However, there was no significance of the abnormal expression rate between ductal carcinoma in situ and atypical ductal hyperplasia tissues groups （X2 = 0.76, P = 0.38; x2 = 0.14, P = 0.70; x2 = 0.81, P = 0.37; X2 = 2.19, P = 0.14） （P 〉 0.05）. （3） There was a significantly difference in the mean E-cadherin, β-catenin and E- cadherin-catenins complex frequency between estrogen receptor ＆ progesterone receptor positive IDC group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was no difference in the mean E-cadherin, β-catenin and E-cadherin-catenins complex frequency between age （_〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm） （P 〉 0.05）. Conclusion： In breast cancer, the expressions of E-cadherin, β-catenin and E-cadherin-catenins complex are abnormally decreased and are correlated with pathology grade, differentiation disturbance and metastasis. E- cadherin and β-catenin may be as the predictors for prognosis. Combined detection may improve accuracy and sensitivity of predicting metastasis and prognosis of breast Cancer.     

Caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous tissues and chronic non-atrophic gastritis

Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.     

Clinical significance of XRCC1 gene expression in human breast cancer and its cell and molecular mechanisms北大核心CSCD

Objective: To investigate the expression of X-ray repair cross complementing 1 (XRCC1) in human breast cancer and its relationship with the clinical characteristics, and to analyze the effects of XRCC1 over-expression on the proliferation and migration of breast cancer MB-231 cells and the molecular mechanism. Methods: The expression level of XRCC1 mRNA in breast cancer cell lines and human breast cancer tissues was detected by real-time fluorescent quantitative PCR. The expression of XRCC1 protein in human breast cancer tissues was detected by immunohistochemistry. The relationship between the expression of XRCC1 protein and the clinicopathological characteristics of breast cancer patients was analyzed. The pcDNA3.1(+)-Flag-XRCC1 plasmids were transfected into breast cancer MB-231 cells for the overexpression of XRCC 1 gene. Then the proliferation activity was detected by CCK-8 and soft agar plate clone formation assay. The cell cycle and apoptosis were detected by FCM method. The cell migration and invasion were detected by Transwell chamber assay. The expressions of cell cycle-, apoptosis- and migration-related proteins were detected by Western blotting. Results: The expression level of XRCC1 mRNA was significantly decreased in most breast cancer cell lines (all P < 0.001). As compared with the normal mammary epithelium and the paired adjacent breast tissues, the expression levels of XRCC1 mRNA and protein were downregulated in human breast cancer tissues (all P < 0.001). The expression level of XRCC1 mRNA was positively correlated with the prognosis of breast cancer patients (γ 2 =0.052, P =0.046), and XRCC1 protein expression was correlated with tumor diameter, lymph node metastasis, histological grade and TNM stage (all P < 0.05). After the overexpression of XRCC 1 gene, the proliferation, colony formation, invasion and migration of breast cancer MB-231 cells were significantly inhibited (all P < 0.01), the cell cycle was significantly blocked in G1 phase (P < 0.001), and the apoptosis rate was significantly increased (P < 0.001). Furthermore, the expressions of p21, p27, Bax, cleaved caspase-3 and E-cadherin were significantly upregulated (all P < 0.001), while the expressions of cyclin-dependent kinase 4/6 (CDK4/6), cyclin D1, Bcl-2, N-cadherin and vimentin were down-regulated (all P < 0.001) in MB-231 cells with XRCC1 overexpression. Conclusion: XRCC1 expression is down-regulated in breast cancer cell lines and tissues, and its expression level is positively correlated with the prognosis of breast cancer patients. Restoring XRCC 1 gene expression can inhibit cell growth, migration and invasion, and can induce apoptosis. So XRCC1 may be a potential tumor suppressor regulating the occurrence and development of human breast cancer. © 2019 by TUMOR.     

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast,and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast(ADH and Peri-PM with ADH),50 specimens of breast in situ ductal carcinomas(DCIS),and 50 specimens of invasive ductal carcinomas(IDC).Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that:the differences among the 4 groups(normal breast tissues,breast premalignant lesions,DCIS and IDC,P<0.05)were significant, and there were also statistically significant differences between any 2 groups(P<0.05)except for the β-tubulin positive expression comparing DCIS versus IDC(P>0.05).In addition,β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH(P<0.05).Following the degree of breast epithelial hyperplasia involved,and its development into carcinoma,the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis(P<0.05),but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression.Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.     

血管内皮生长因子-D在胃癌中表达的意义

Objective： To investigate the expression of vascular endothelial growth factor D （VEGF-D） in gastric cancer and its relationship with lymph node metastasis. Methods： 100 cases of gastric carcinoma tissues （50 cases with lymph node metastasis, 50 cases negative） and 30 cases of normal gastric tissues were gathered to detect the expressions of VEGF-C and D proteins by immunohistochemistry. Results： VEGF-C and D were revealed in cytoplasm of gastric carcinoma tissues and normal gastric tissues. The positive rates of VEGF-C and D expressions were significantly higher in gastric cancer tissues than those in the normal ones （51%, 60% vs 10%, 20% respectively; both P 〈 0.05）. There were significant correlations between the positive expression of VEGF-D and lymph node metastasis, lymphatic invasion, positive expression of VEG F-C, but not with tumour size, tissue differentiation, and venous invasion. Conclusion： The expression of VEGF-D is closely related to lymph node metastasis in gastric carcinoma.     

RELATIONSHIP BETWEEN EXPRESSIONS OF P38 PROTEIN IN HUMAN BREAST CARCINOMA AND LYMPH NODES METASTASIS

Objective： To detect the change of p38 protein expression and investigate the relationship of p38 and lymph nodes metastasis in human breast carcinomas. Methods： Sixty breast cancer cases were checked by S-P immunohistochemistry technique and 30 breast cancer cases were examined by Western Blot. Results： Immunohistochemical results showed that p38 protein was observed in breast cancer and normal cytoplasm. P-p38 was positive in nucleus in breast cancer. P38 protein expressed positively in 29 out of 38 patients who had lymph nodes metastasis （positive rate 76.3%） and in 9 out of 22 patients who had no lymph nodes metastasis （positive rate 40.9%）. There was a significant difference between these two groups （P〈0.01）. The positive rate of p-p38 in patients who had lymph nodes metastasis was 68.4%, and the positive rate in patients who had no metastasis was 36.4%, and there was a significant difference between these two groups （P〈0.05）. The result of western blot showed that the protein contents of p38 and p-p38 in patients with metastasis was higher than those in patients without metastasis （P〈0.05）. P38 and p-p38 protein expressions had relation with clinical pathological grades in breast cancer, higher in grade Ⅲ than in grade Ⅰ, Ⅱ （P〈0.05）, while had no relation with patients＇ age and tumor size （P〉0.05）. Conclusion： p38 and p-p38 protein expressions had relationship with lymph nodes metastasis and the levels of p38 and p-p38 protein expression in groups with lymph nodes metastasis were higher than in groups without lymph nodes metastasis. P38 and p-p38 protein expressions had relationship with clinical grades and had no relationship with patients＇ age and tumor size.     

Overexpression of Gli1 in cancer interstitial tissues predicts early relapse after radical operation of breast cancer

Objective:To investigate whether Gli1 expression is important in relapse after radical operation of breast cancer.Methods:Using immunohistochemistry,Gli1 expression was analyzed in human primary breast cancer(n=284) and paracancerous tissues(n=20),and also in local lymph nodes(n=28) and metastatic lymph nodes(n=28).Results:Initial analysis of Gli1 expression in a small cohort of 20 breast tumors and their paracancerous tissues showed a tendency towards Gli1 overexpression in breast cancer tissues(P<0.001).Further,Gli1 expression in 284 breast cancer tissue samples was analyzed and a significant correlation was found between increased expression of nuclear Gli1 and unfavorable recurrence-free survival(RFS)(P<0.05).The nuclear expression of Gli1 in metastatic lymph nodes following relapse after radical operation was much higher than that in the local lymph nodes of primary carcinoma(P<0.05).Most interestingly,the expression of Gli1 was much higher in the interstitial tissues of the relapsed group than of the non-relapsed group(P<0.001).Conclusions:Breast cancer shows a high prevalence of Gli1 expression,which is significantly correlated with aggressive features and unfavorable RFS.Nuclear Gli1 overexpression,especially in the interstitial tissues,signified early relapse after radical operation of breast cancer.     

Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.     

Survivin基因在乳腺癌组织中的表达及其与HER2、p53基因表达的关系

Objective： To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods： The expression of survivin, mutant p53, and C-erbB-2 was detected in 62 specimens of breast carcinoma by using streptavidin-peroxidase （SP） immunocytochemical assay. Results： Among the 62 cases of breast carcinoma, the positive rate of survivin was 67.7%; 35.5% of the tumors were positive for p53; and 37.1% for C-erbB-2 overexpression. Survivin expression was independent on patient＇s menopausal status, tumor histology, clinical stage, tumor size, lymph node metastasis, and estrogen receptor level. Although survivin expression was not correlated with p53 mutations, the positive expression of survivin was associated with C-erbB-2 overexpression （87.0% vs 56.4%, P〈0.05）. Conclusion： The positive expression of survivin was independent on p53 mutation, but dependent on the overexpression of C-erbB-2. C-erbB-2 might up-regulate the expression of survivin.     

Relationship between Expression of Cell Adhesion Molecules and the Metastatic Mechanism in Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To explore the expression and the function of cell adhesion molecules in invasive micropapillary carcinoma (IMPC) of the breast, and to investigate the metastatic mechanism of IMPC. METHODS The expression of E-cadherin, α-catenin and β-catenin was detected by imrnunohistochemical staining in 64 cases of IMPC, and compared with that of invasive ductal carcinoma (IDC). RESULTS E-cadherin and β-catenin were mainly expressed on the cell membrane of tumors, and cc-catenin was expressed in the cytoplasm and/or on the cell membrane. The expression of E-cadherin in IMPC was significantly higher than that in IDC. Furthermore, the expression of E-cadherin was mainly on the intercellular contact surface of the tumor cell clusters in IMPC, while that on the outer surface of the tumor cell clusters decreased or could not be detected. The degree of lymph nodes metastases in IMPC was significantly higher than that in IDC. The co-expressions of α-catenin and β-catenin in cases of lymph nodes metastases along with the expression of E-cadherin in IMPC were significantly higher than that in IDC. CONCLUSIONS These findings indicated that the adhesiveness of the intercellular contact surfaces of tumor clusters in IMPC was strong, while that of the outer surface of tumor clusters was decreased or lost. It is suggested that the adhesive characteristic of the cells in IMPC might play an important role in its higher metastatic potential.     

Correlation between Expression of P38 MAPK-Signaling and uPA in Breast Cancer

OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase(p-p38)and uPA and the correlation of their expression with breast cancer clinicopathological characteristics,and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells. METHODS Immunohistochemistry(S-P) was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues.Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells,and uPA expression a er treatment with SB203580,a specific inhibitor of p38 MAPK. RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively.The expression of p-p38 was positively related to the expression of uPA(r=0.316,P<0.05).The expression of p-p38 and uPA was related to lymph node metastas is and the TNM stage(P<0.05),but it was not related to the patient’s age or tumor size(P>0.05).The expression of p-p38 and uPA in MDA-MB-231 cells was higher than that in MCF-7 cells.SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression. CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression,and it may be an important process in breast cancer invasion and metastasis.     

The Significance of CXCR4 Expression for the Prediction of Lymph Node Metastasis in Breast Cancer Patients

OBJECTIVE The chemokine receptor(CXCR4)CXC chemokine receptor 4)plays an important role in cancer metastasis.We therefore studied differential expression of the CXCR4,as well as that of the biomarker HER2,so as to evaluate whether these biomarkers can be used to predict axillary lymph node metastasis in breast cancer patients. METHODS Immunohistochemistry was used to evaluate the CXCR4 and HER2 expressions and to examine the paraffin sections of the breast cancers at various stages.Positive lymph node expression was found in 80 of the cases,and in 7 there was negative expression. RESULTS Compared to the cases with negative lymph nodes, there was a high expression of CXCR4(26.3% vs.14.3%,P=0.013), and an over-expression of HER2(28.8% vs.14.3%,P=0.011). Moreover,there was a direct correlation between the CXCR4 and HER2 expressions and the tumor staging(P=0.000)and lymph node metastasis(P=0.032).When the two biomarkers,i.e.CXCR4 and HER2,were concurrently labeled,a high expression of one of the biomarkers could be seen in the cases with positive lymph nodes(51.3% vs.28.6%,P<0.003). CONCLUSION The chemokine receptor,CXCR4,is a new-type biomarker in predicting axillary lymph-node metastasis in breast cancers.Compared with the other markers,such as HER2 etc., assessment of CXCR4 can improve the prediction of the presence and extent of lymph node involvement.     

HIF-1α和VEGF-C在乳腺癌淋巴管生成中的作用机制

Objective To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-C (VEGF-C) and the correlations with clinic parameters, and to make sure the effect of DOI:10.3760/cma.j.issn.1673-422X.2013.10. 基金项目：安徽省卫生厅自然科学基金（09C230）作者单位：241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜）,病理科（李勇）通信作者：赵迎春,E-mail: lcy0508@hotmail.com 联系人: 赵迎春 lcy0508@hotmail.com 电话：05533909558 手机：18155317401 the two genes in the lymphangiogenesis and lymph node metastasis of breast cancer. Methods The expressions of HIF-1α and VEGF-C were investigated by means of immunohistochemistry in samples from 78 cases of breast cancer and 20 cases of breast benign lesions. The density of the lymphatic microvessels immunohistochemically stained by D2-40 antibody was calculated. The relationships between HIF-1α, VEGF-C, LVD and clinicopathological parameters were analyzed statistically. Results HIF-1α expression occurred in 52 out of the 78 tumor samples (66.67%), while VEGF-C expression was observed in 41 out of the 78 tumor samples (52.56%). HIF-1α and VEGF-C expressions in breast cancer were significantly higher than those in beingn disease (15% and 10%; χ²=17.26, P=0.000; χ²=11.71, P=0.001). The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (χ²=5.80, P=0.016; χ²=7.26, P=0.007) as well as late TNM classification (χ²=8.51, P=0.004; χ²=6.02, P=0.014), disregarding the patient’s age, tumor diameter, histological grade and pathologic type (P＞0.05). In addition, HIF-1α expression was positively correlated with VEGF-C expression (r=0.254, P=0.025). Higher LVD was found in both high HIF-1α and high VEGF-C expression cases (t=2.19, P=0.017; t=3.25, P=0.001). Conclusion HIF-1α may play a crucial role in the lymphangiogenesis and lymph node metastasis by regulating the expression of VEGF-C in breast cancer. Therefore, HIF-1α may become a particularly promising target for controlling lymph node metastasis in breast cancer.     

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features.METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast (ADH and Peri-PM with ADH), 50 specimens of breast in situ ductal carcinomas (DCIS), and 50 specimens of invasive ductal carcinomas (IDC). Thirty specimens of normal breast tissues served as a control group.RESULTS Immunohistochemical analysis showed that: the differences among the 4 groups (normal breast tissues, breast premalignant lesions, DCIS and IDC, P ＜ 0.05) were significant,and there were also statistically significant differences between any 2 groups (P ＜ 0.05) except for the β-tubulin positive expression comparing DCIS versus IDC (P ＞ 0.05). In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH (P ＜ 0.05). Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency.We also found a significant positive relationship of β-tubulin expression with lymph node metastasis (P ＜ 0.05), but no significant correlation with histological grading and nuclear grade.CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.     

Expression of Cyclin E and Its Relationship with the Prognosis of Patients with Breast Cancer

Objective： To investigate the expression of cyclin E in breast cancer tissues and its relationship with prognosis of the patients with breast cancer. Methods： The expression of cyclin E, HER-2/neu, nm23-H1 and actin was detected in 80 breast cancer tissues and 18 benign breast tumor tissues by immunohistochemical methods. The relationship between cyclin E and the remaining genes or the clinical data of the patients with breast cancer was analyzed. Results： The over expression rate of cyclin E in malignant tissues was obviously higher than that in benign tumor tissues （P〈0.01）. The over expression of cyclin E in later stage of disease was higher than that in early stage of disease （P〈0.05）. The expression of cyclin E in ER positive tissues was lower than that in ER negative tissues （P〈0.05）. The expression of cyclin E in PR positive tissues and PR negative tissues had no significant difference （P〉0.05）. The expression of cyclin E in HER-2/neu positive tissues was higher than that in HER-2/neu negative tissues （P〈0.05）. And the expression of cyclin E in ER, PR and HER-2/neu all positive tissues was much higher （P〈0.01）. There was no significant difference in the expression of cyclin E between nm23-H1 positive tissues and nm23-H1 negative tissues （P〉0.05）. The expression of cyclin E in actin positive and continuous distribution tissues was lower than that in actin negative or discontinuous distribution tissues （P〈0.05）. Conclusion： The expression of cyclin E has a strong correlation to the prognosis of the patients with breast cancer.     

Over-expression of EGFR in Breast Cancer

Objective： To explore the relationship of overexpression of epidermal growth factor receptor （EGFR） in occurrence, development and treatment of breast cancer. Methods： Samples of 46 breast adenoma tissues and 86 breast cancer tissues were regularly dehydrate-fixed, embedded in paraffin, sliced in to 5μm thick, stained with SABC immunohistochemistry and coloured with DAB. Results： The positive staining of EGFR was shown as brown- yellow and distributed in cytoplasm. The positive rates in the tissues of breast adenosis and breast cancer were 17.04% （6/46） and 56.98% （49/86） respectively. The positive rates of EGFR in the tissue of invasive ductal carcinoma was 64.49% （41/59）, which was significantly higher than that in in situ carcinoma （P〈0.05）. The positive rate of lymph metastasis group was higher than that in non-lymph metastasis group （P〈0.05）. Conclusion： The overexpression of EGFR was related with occurrence, lymph metastasis and pathologic types of breast cancer. The examination of EGFR in the breast cancer can serve as a guidance for target chemotherapy.