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Objective To explore the expression of matrix metalloproteinase-9 (MMP-9) in breast carcinoma and the relationship between the expression and clinical pathological characterization.Methods Specimens taken from 50 fresh resected breast carcinoma tissue and 16 normal breast tissue were selected.Tissue sections were stained by EnVisionTM imnunohistochemistry with MMP-9 as monoclonal antibody.The expression of MMP-9 in breast carcinoma and the relationship between the expression and clinical pathological characterization were studied.Results The positive rate of MMP-9 breast cancer carcinoma was 59.32％,which was significantly higher than that of normal breast tissue 9.62％,with statistical significance (P ＜ 0.01).The average rank and score of MMP-9 in the metastatic tissue of breast carcinoma were higher than that of no metastatic breast cancer tissue (P ＜ 0.01).Conclusions MMP-9 may be related to the destruction of extracellular matrix and basement membrane near the surface of breast cancer cells,thereby promoting the invasion and metastasis of breast cancer.
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Objective To explore the expression and correlation of Fascin-1 and epidermal growth factor receptor (EGFR) in hormone receptor-positive breast cancer.Methods The immunohistochemical technique,EnVision method,was used to evaluate the expression of Fascin-1 and EGFR in 294 cases of hormone receptor-positive breast cancer,which contains 290 cases of estrogen receptor (ER) positive and 244 cases of progestrone receptor (PR) positive.According to ER,PR,Epidermal growth factor receptor 2 (HER2),and Ki-67 status,all cases of hormone receptor-positive breast cancer were categorized into 2 subtypes:160 cases of luminal A and 134 cases of luminal B.Results Fascin-1 and EGFR protein positive rates in hormone receptor-positive breast cancer was 13.9％ (41/294) and 30.6％ (90/294),respectively.Fascin-1 positive rate was significantly higher in EGFR positive cases (30.0％,27/90) than in EGFR negative cases (6.9％,14/204) (x2 =27.857,P =0.000).In the ER positive and PR positive cases,Fascin-1 positive rates were both significantly higher in EGFR positive cases than in EGFR negative cases (x2 =29.23,P =0.000;x2 =27.596,P =0.000,respectively).In the Luminal A and Luminal B subtype,Fascin-1 positive rates were also both significantly higher in EGFR positive cases than in EGFR negative cases (x2 =23.247,P=0.000;x2 =5.325,P=0.021,respectively).Conclusions EGFR signal pathway may positive regulate Fascin-1 expression in hormone receptor-positive breast cancer.
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The breast cancer is the most common malignant tumor of women, and its treatments were widely explored.A lot of studies have confirmed that the abnormal activation of WNT/ beta-catenin signaling pathway and the abnormal expression of miRNA are closely related to the occurrence and development of breast cancer.miRNA could target the regulation of WNT/beta-catenin signaling pathway and affect the occurrence and development of many human tumors as an endogenous non-coding small molecule RNA.Therefore, the mechanism of WNT/beta-catenin signaling pathway in breast cancer and its interaction with miRNA may provide new ideas for the treatment of breast cancer.The article reviewed the composition of the WNT/beta-catenin signaling pathway and the role of this signaling pathway and its interaction with miRNA in the pathogenesis and progression of breast cancer.
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Objective To investigate the relationship between miR-411 and breast cancer,and the expression of miR-411 and its effects and mechanism research on proliferation and metastasis in breast cancer.Methods Real-time polymerase chain reaction (RT-PCR) was used to detect the expression of miR411 in breast cancer cells and tissues.Methyl thiazolyl tetrazolium (MTT),clone formation assay and Transwell assay were used to detect the effect of miR-411 expression on the proliferation,migration and invasion in breast cancer cells.The effect of miR-411 on growth factor receptor-bound protein 2 (GRB2) expression in breast cancer cells was detected by RT-PCR and Western blot.The direct effect of miR-411 target on GRB2 was detected by dual luciferase reporter assay.MTT,clone formation assay and Transwell assay detect the effect of GRB2 expression on the proliferation and invasion in breast cancer cells.Detection the effect high expression of miR-411 on GRB2 downstream signaling pathway related molecules expression in breast cancer cell with Western blot.Results The expression of miR-411 in breast cancer tissues was significantly lower than that in adjacent non-cancerous tissues (P ＜ 0.05).The expression of miR-411 in breast cancer cells SK-BR-3,BT-549 and MDA-MB-231 was significantly lower (P ＜ 0.05).Compared to the negative control group,the transfection of miR-411 mimic inhibited the proliferation,migration and invasion of MDA-MB-231 breast cancer cells (P ＜ 0.05).Targetscan showed that miR-411 could bind to GRB2 3'UTR at position 741-747.Compared with the negative control group,GRB2 3'UTR wild-type plasmid and miR-411 co-transfection reduced the fluorescence activity (P ＜ 0.05).Transfection of siGRB2 significantly reduced the expression of GRB2 protein in MDA-MB-231 breast cancer cells (P ＜ 0.05).Compared to the negative control group,the inhibition of GRB2 expression reduced the proliferation and the number of colony formation of MDA-MB-231 breast cancer cells (P ＜ 0.05).Transwell assay showed that transfection of siGRB2 significantly reduced the number of invasive cells in MDA-MB-231 breast cancer cells (P ＜ 0.05).Conclusions miR-411 is related closely to the occurrence and development of breast cancer,miR-411-GRB2-Ras axis is expected to become a new target for biological treatment of breast cancer.
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Objective To investigate the expression and clinical significance of lactate dehydrogenase A (LDHA) in breast cancer.Methods Tissue samples of 76 breast cancers and corresponding paired adjacent normal tissues were collected and made into tissue micrcarrays (TMAs).Immunohistochemistry (IHC) analysis was performed to detect the expression of LDHA and further analyzed the correlation of LDHA expression and clinicopathological variables and prognosis of breast cancers.Results LDHA was frequently upregulated in breast cancer tissues compared to the normal breast tissues (P ＜ 0.05).High LDHA expression was associated with distant metastasis (P ＜ 0.05) and worse patient prognosis (P ＜ 0.05).Conclusions LDHA is closely related to the occurrence and clinical progress of breast cancers.LDHA might be a potential novel molecular marker for diagnosis,prognosis and therapy in breast cancers.
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Objective To investigate the expression of microRNA-451 (miR-451) in female invasive ductal carcinoma (IDC) and its roles in tumor cell invasion.Methods Forty five IDC tissues and matched tumor adjacent tissues were collected between January and December in 2014.The expressions of miR-451 in tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR).The relationship between long noncoding RNA taurine regulated genes 1 (lncRNA-TUG1) and clinical features was analyzed by student-t test.miR-451 mimics was transfected into MDA-MB-231 cells.Transwell assay was used to measure cell invasion ability.The expression of c-myc,a potential target of miR-451,and its downstream genes,matrix metalloproteinase (MMP)-2 and MMP-9 were detected by qRT-PCR and Western-blot.Resuts The expression of miR-451 was significantly lower in IDC tissues than in matched tumor adjacent tissues (P ＜ 0.05).Low expression of miR-451 was positively associated with lymphatic metastasis (P ＜ 0.05) and advanced tumor node metastasis (TNM) stage (P ＜ 0.05).Up-regulation of miR-451 in MDA-MB-231 cells could significantly suppress cell invasion ability (P ＜0.05).c-myc expression was down-regulatedwhen miR-451 was transfected (P ＜0.05).As downstream genes of c-myc,the expressions of MMP-2 and MMP-9 were suppressed.Conclusions miR-451 is down-regulated in IDC tissues and associated with cell invasion.miR-451 might inhibit IDC progression by inhibiting c-myc/MMP axis.
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Objective To explore the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in anthracycline-based chemotherapy-related cardiotoxicity of breast cancers.Methods A total of 135 breast cancer patients was analyzed if NT-proBNP was associated with chemotherapy-related cardiotoxicity.The level of NT-proBNP in the diagnosis of cardiotoxicity was assessed.Results A total of 22 patients (16.29％) had subsequent claims for cardiotoxicity events.NT-proBNP in cardiotoxicity group was significantly higher than that non-cardiotoxicity group (P ＜ 0.05).According to receiver operating characteristic (ROC) curve, the cut-off value of NT-proBNP was set at 350 pg/ml, specificity and sensitivity were 70.32％ and 82.58％ , respectively.Positive and negative predictive values were 78.12％ and 65.45％, respectively.Conclusions The present study is to confirm excellent clinical value of NTproBNP on cardiotoxicity.The level of NT-proBNP for early detection of cardiotoxicity has good prospects for high risk patients.
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Objective To investigate the expression of matrix metalloproteinase 2 (MMP2) and MMP9 in the breast cancer and its relationship with tumor invasive potentiality,node metastasis and prognostic significance.Methods 130 cases of breast cancer and 10 cases of breast benign disease were studied by immunohistochemical staining with MMP2,MMP9 monoclonal antibodies.Results The positive expression rate of MMP2 and MMP9 were 83.08％ (108/130) and 71.54％ (93/130) in the breast cancers,which was significantly higher than those in breast benign disease ( P ＜0.01 ).The expressions of MMP2 and MMP9 obviously increased with tumor sizes and clinical staging( P ＜0.05,P ＜ 0.01 ).Over expression of MMP2 and MMP9 in the breast cancers with axillary lymph node metastases were significantly higher than those without lymph node metastases ( P ＜ 0.01 ).Conclusions The expression of MMP2 and MMP9was closely correlated to lymph node metastasis,and may act as markers for lymph node metastasis and prognostic in breast cancer.
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Objective To research the expression change and the sense of histone acetylation and p21WAF1 protein in breast cancer. Methods Pathological morphologic changes of breast cancer were identified by H. E. staining. Immunohistochemical study for p21WAF1 protein expression was performed on 80 breast cancers and 80 normal breast tissues. The expressions of acetylated histone H3, H4 and p21WAF1 protein in 80 breast cancers and 80 normal breast tissues were analyzed by Western blot. Results H.E. staining discovered that the tissue structure and cell morphous of breast cancer had visible atypia, compared with normal breast tissues. The immunohistochemical results displayed that the positive expression of p21 WAF1 in 80 breast cancers and 80 normal breast tissues was 49 cases(61.25 %) or 3 cases (3.75%), respectively. There was significantly difference in the expression level between the 80 breast cancers and 80 normal breast tissues (P ＜ 0. 05). The expression levels of p21WAF1 protein in breast cancer tissues were higher than that in normal breast tissues, 0. 78 ± 0. 095 or 0. 65 ± 0. 055, respectively. The expression levels of acetylated histone H3, H4 protein in normal breast tissues were higher than those in breast cancer tissues. H3 was 2. 35 ± 0. 340 or 1.07 ± 0. 067, respectively, H4 was 3.44 ± 0. 202 or 1.11 ± 0. 086, respectively. There was significantly difference in the expression levels between the 80 breast cancers and 80 normal breast tissues (P ＜0. 01). Conclusions The occurrence and development of breast cancers may be related to the expression change of histone acetylation and p21WAF1 protein.
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Objective To investigate the expressions of Snail mRNA and E-cad mRNA in invasive ductal carcinoma and their clinical significance. Methods The expression of Snail mRNA and E-cad mRNA were detected on mammary gland hyperplasia (30cases), intraductal breast carcinoma(30cases) and invasive ductal carcinoma (70cases)by in situ hybridization. Results The positive expression rate of Snail mRNA and E-cad mRNA in mammary gland hyperplasia, intraductal breast carcinoma and invasive ductal carcinoma were 23. 3% ,46. 7% ,81.4% and 96. 7% ,66. 7% ,35.7% ,respectively. There was significant difference among them(P ＜ 0. 01). There was difference between Snail mRNA and E-cad mRNA in the same group(P ＜0. 05). Snail mRNA was not related to age, tumor size or histopathological grade (P ＞0. 05) ,but it was related to lymphatic metastasis (P ＜0. 01). E-cad mRNA was not related to age, tumor size(P ＞0. 05),but it was related to lymphatic metastasis and histopathological grade(P ＜0. 01). There were positive relationship between Snail mRNA and E-cad mRNA(r = -0. 56, P =0. 00). Conclusions The overexpression of Snail mRNA and low expression of E-cad mRNA were involved in the infiltration and metastasis of breast carcinoma, and they were related to lymphatic metastasis. Therefore, the test of the expression of them were valuable in predicting the prognostic and metastasis of breast carcinoma.
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Objective To investigate the expression and clinical significance of CXCR3/CXCL10in human cancer.Methods CXCR3 and CXCL10 were detected in 60 paraffinic tissues of patients with primary breast cancer,20 of mammary fibroma and 20 of mastopathy by immunohistochemistry S-P method and two stage method.Results The expression of CXCR3 (40/60,66.7％ ) and CXCL10 (45/60,75％)in breast cancer was higher than that in mastopathy [CXCR3(8/20,40％ )x2 =4.44,P =0.035 ;CXCL10( 10/20,50％ )x2 =4.36,P =0.037)].The expression of CXCR3 was related to status of axillary lymph node metastasis,clinical stage and the expression of HER-2 (x2 =4.15,P =0.042; x2 =7.74,P =0.021 ;x2 =4.27,P =0.039).The expression of CXCR3 had positive relationship to the number axillary lymph node metastasis( rs =0.375,P =0.003 ),clinical stage ( rs =0.451,P =0.000).Conclusions CXCR3 may be related to the progression and metastasis of breast cancer,and it may be used as a marker of breast cancer prognosis.
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Objective To investigate the'expression of Survivin in breast cancer tissue microarray, and its implication to clinic pathology and prognosis. Methods The expression of Survivin was studied in 80 cases of breast disease tissues ( 18 cases of hyperplasia of mammary glands and 62 cases of breast canc-er) and 20 cases of adjacent normal tissues by S-P immunohistochemisty to analysis the relationships be-tween its expression and history grade, clinic stage and lymphaden metastasis. Results The positive rates of Survivin were 0(0/20) in normal mammary glands, 33. 3% (6/18) in hyperplasia of mammary glands and 72. 5% (45/62) in breast cancer. There were significant difference between them (X~2= 34. 62, P <0. 01 ). The expression of Survivin was closely correlated to the stage and lymphaden metatasis and survival time ( P <0.05 or P <0.01), and it was negatively correlated to the histological grade ( P >0.05).Conclusions The expression of Survivin shows an ascending tendency in the carcinogenesis and progres-sion of breast cancer. The Survivin can promote the invasion and the metastasis of the cancer cell, and it is closely correlated to the prognosis.
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Objective To study the correlation of EMMPRIN and VEGF-C expression with invasion and metastasis of breast carcinoma. Method The expression of EMMPRIN and VEGF-C was detected by immunohistochemical technique in 21 cases hyperplasia of mammary glands, 10 cases of in-tubule carcinoma and 68 cases invasive carcinoma. Results The positive rate of EMMPRIN expression in hyperplasia of mammary glands, in-tubule carcinoma and invasive carcinoma were 4. 76% (1/21), 40. 00% (4/10)73.53% (50/68), respectively;Significant difference was found among three groups ( P < 0.01 ). The positive rate of VEGF-C expression in hyperplasia, in-tubule carcinoma and invasive carcinoma were14. 29% (3/21) ,60. 00 (6/10) ,77.94% (53/68), respectively. The positive rates of VEGF-C expression in situ and invasive ductal carcinoma were remarkably higher than that of hyperplasia of mammary glands ( P <0. 01 ). The expression of EMMPRIN significantly correlated with the expression of VEGF-C in breast tubule carcinoma ( rs =0. 390, P <0. 01 ), Lymph nod metastasis and the number axillary Lymph nod metastasis were related to EMMPRIN and VEGF-C ( P < 0. 01 ). Conclusion The over-expression of EMMPRIN and VEGF-C were important elements to promote the invasiveness and metastasis of breast carcinoma. Synergistic effect between EMMPRIN and VEGF-C may take place in lymph node metastasis of breast carcinoma.
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Objective To analyze the pathologic and biology features and prognosis of HER-2,ER and PR negative breast cancer(TNBC).Methods Clinic pathologic data of 329 breast cancer patients was retrospectively analyzed. The expression of HER-2, ER, PR and P53 was determined by immunohistochemistry. The patients were divided into three groups, including TN group [ HER-2 (-), ER (-), PR (-)], HER-2 group [HER-2(+),ER(-),PR(-)] and HR group [ER(+),PR(-) or (+),HER-2(-) or (+) ].The pathology and biology features and P53 masculine expression of the three groups were compared.The 5-year overall survival and disease free survival were analyzed by Kaplan-Meier method.Results Of the 329 patients, 20.97% (69/329) was TN group, 34.04% (112/329)was HER-2 group, and 44.98% (148/329) was HR group.The percentage of with lymph node metastasis in TN group 55.07% (38/69) was higher than that in HER-2 group 42.86% (48/112) and HR group 43.24% (64/148) (χ2 = 12.57, P ＜ 0.05).The rates of P53 positive, operation recurrence and metastasis in TN group were 44.93%, 27.54% and 20.29%, which were higher than that in HER-2 group (20.54% ,16.07%,16.96%) and HR group (18.24%, 12.84%, 10.81%) (χ2=12.23, 8.36, P ＜0.05).The ratio of tumor ≥5cm, Ⅲ stages, Ⅲ grade and soakage canula cancer among three groups had statistical difference (χ2 = 7.25,8.79,9.23,8.48, P ＜ 0.05).The 5-year overall survival in three groups were 75.36%,82.14% ,85.14% and disease free survival were 68.12% ,78.57% ,82.43% (χ2 =8.52, P ＜0.05).Conclusion The pathology and biology traits of TNBC were high rate of P53 (+) and recurrence and lymph node metastasis.The most important factor for poor prognosis of TNBC was the low rate of disease free survival for 5 years.
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Objective To study the expression of VEGF, MMP-2 and MMP-9 in benign and malignant lesions of breast and their effects on breast carcinoma's invasiveness and metastasis. Methods VEGF,MMP-2 and MMP-9 expression was detected by SP method in 20 breast fibroadenoma and 12 normal breast specimens taken from non-cancerous regions adjacent to breast cancer tissue and 38 breast carcinomas. Results The expression rate of VEGF, MMP-2 and MMP-9 in breast carcinoma was remarkably higher than those in normal breast tissue and breast fibrogdenoma (63.2% vs 25.0% and 30. 0% ,78. 95% vs 33.3% and 35.0% and 71.1% vs 41.7% and 45.0% ,respectively; P ＜0.05). There was a correlation between VEGF, MMP-2 and MMP-9 expression and nodal metastasis ( P ＜0.05). High expression of VEGF, MMP-2 and MMP-9 was correlated with pathological grade ( P ＜ 0.05, respectively). The overexpression of VEGF was related with those of MMP-2 and MMP-9 in breast cancer( VEGF and MMP-2:rs =0.541, P ＜0.01 ;VEGF and M M P-9: rs = 0.11, P ＜ 0.01; MMP-2and M MP-9: rs= 0P ＜ 0.01 ). Conclusion VEGF,MMP-2 and MMP-9 overexpression is strongly related to the invasiveness and metastasis of breast carcinoma, which might be valuable in evaluating tumor invasion and metastasis.