转化生长因子β1在乳腺癌中的表达及其预后意义

目的研究转化生长因子β1(TGFβ1)在乳腺癌中的表达及其与乳腺癌预后的关系.方法对84例随访5年以上乳腺癌用免疫组化法检测TGFβ1蛋白表达.结果TGFβ1表达与乳腺癌肿瘤大小、组织学分级、腋淋巴结转移等无显著相关性.与乳腺癌预后呈负相关,TGFβ1阴性患者的术后五年生存率为74.19%,明显高于TGFβ1阳性患者的50.91%(P＜0.05).将TGFβ1与腋淋巴结转移状况合并,可增大预后判断价值.Cox多因素分析表明TGFβ1是相对独立的预后因素.结论TGFβ1是乳腺癌的预后不良因素之一,临床检测乳腺癌TGFβ1蛋白表达可作为乳腺癌生物学行为和预后判断的新指标.     

转录因子Sp1在乳腺癌组织中的表达及其预后意义

背景与目的:已知转录因子Sp1参与几乎所有的细胞功能,包括细胞增殖、凋亡、分化和新生物的转化,在恶性肿瘤侵袭与转移中发挥重要作用,但不同来源肿瘤的Sp1表达也不尽相同.本研究旨在探讨Sp1在乳腺癌组织中的表达及其与乳腺癌侵袭、转移及预后的关系.方法:用免疫组化EnVision法检测60例乳腺癌及12例癌旁乳腺组织中Sp1的表达情况.结果:Sp1在乳腺癌组织中的阳性率为71.67%(43/60),在癌旁乳腺组织中的阳性率为33.33%(4/12).乳腺癌组织中Sp1表达与乳腺癌患者TNM分期呈正相关(r=0.349,P＜0.05),与癌组织浸润呈正相关(r=0.407,P＜0.01),与淋巴结转移呈正相关(r=0.314,P＜0.05).单因素生存分析显示乳腺癌组织Sp1阳性组的总生存率低于阴性组(分别为41.86%和82.35%,P＜0.05).Cox模型多因素分析显示乳腺癌组织Sp1表达、TNM分期、癌组织浸润及淋巴结转移是影响乳腺癌患者预后的独立因素.结论:Sp1可能参与了乳腺癌的侵袭与转移,是乳腺癌预后不良因素之一;检测Sp1的表达并结合肿瘤浸润和临床分期分析能提高对乳腺癌患者预后判断的准确性.     

Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer

Background  

The putative tumor metastasis suppressor 1(MTSS1) is an actin-binding scaffold protein that has been implicated to play an important role in carcinogenesis and cancer metastasis, yet its role in the development of gastric cancer has not been well illustrated. In this study, we detected MTSS1 expression and explored its clinical significance in gastric cancer.     

The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer

There is a need for new biomarkers to more correctly identify node-negative breast cancer patients with a good or bad prognosis. Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) is a membrane-bound protein that is associated with cell spreading, integrin activation and exocytosis. Three hundred and five operable T(1,2)N(0)M(0) lymph node-negative breast cancer patients (median follow-up time 121?months, range 10-178?months) were evaluated for MARCKSL1 expression by immunohistochemistry and quantitative real-time PCR. The results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation), using single (Kaplan-Meier) and multivariate survival analysis (Cox model). Forty-seven patients (15?%) developed distant metastases. With single and multivariate analysis of all features, MARCKSL1 protein expression was the strongest prognosticator (P?相似文献   

Correlation and prognostic value of SIRT1 and Notch1 signaling in breast cancer

Background

SIRT1 expression and Notch1 signaling have been implicated in tumorigenesis in many cancers, but their association with survival in breast cancer has not been determined. The purpose of this study was to assess the possible prognostic value of SIRT1, N1IC, and Snail expression in breast cancer patients.

Methods

Immunohistochemistry was performed to examine the expression of SIRT1, N1IC, and Snail, and the combined expression of SIRT1 and N1IC, using tissue microarrays containing breast cancer tissue and matched adjacent normal breast tissue from 150 breast cancer patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of SIRT1, N1IC, Snail and combined SIRT1/N1IC expression, in addition to other clinicopathological factors, including grade, lymph node status, disease stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 receptor status in breast carcinoma patients.

Results

SIRT1, N1IC, and Snail were all found to be highly expressed and an inverse correlation between SIRT1 and N1IC in breast cancer tissue. The three markers significantly correlated with lymph node status. Patients with low SIRT1 expression exhibited shorter overall survival (OS) and disease-free survival (DFS), and patients with combined low expression of SIRT1 and high expression of N1IC had the worse OS and DFS. Univariate and multivariate survival analysis revealed that low expression of SIRT1 and SIRT1-low/N1IC-high expression were independent prognostic factors for poor survival.

Conclusions

These results suggest that low expression of SIRT1 or the combined low expression of SIRT1 and high expression of N1IC could be used as indicators of poor prognosis, and may represent novel therapeutic targets in breast cancer.

     

Testin is a tumor suppressor and prognostic marker in breast cancer

The testin (TES) gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. In the present study, we aimed to investigate the candidate tumor suppressor function of TES and explore its correlations to clinicopathologic features and prognosis in breast cancer. In clinical samples, we showed that the expression of TES decreased gradually from normal through ductal hyperplasia without atypia, atypical ductal hyperplasia, and ductal carcinoma in situ, to invasive ductal carcinoma. To explore the possible tumor suppressing function of TES, the expression of TES in breast cancer cells was manipulated by ectopic expression or by RNAi. We revealed that ectopic TES expression significantly inhibited cell proliferation, invasive ability, and angiogenesis, whereas knockdown of TES by RNAi enhanced cell proliferation, invasive ability, and angiogenesis. In an animal model, TES markedly inhibited breast cancer cell xenograft formation in athymic nude mice and reduced breast cancer cell metastasis to lung. Moreover, we revealed that TES inhibited the invasion and angiogenesis of breast cancer partially through miR‐29b‐mediated MMP‐2 inhibition. Using the tissue microarray of breast cancer from Yale University, we found that lower TES expression was an independent prognostic factor for shorter overall survival and disease‐free survival with univariate and multivariate analyses. Taken together, these data suggest that TES, as a valuable marker of breast cancer prognosis, plays an important role in the development and progression of breast cancer. TES may be an effective novel target in breast cancer prevention and treatment.     

Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer

Introduction  

Bcl-2 antanogene-1 (Bag-1) binds the anti-apoptotic mediator Bcl-2, and enhances its activity. Bcl-2 and Bag-1 are associated with chemotherapy resistance in cancer cells. Drugs that target Bcl-2 are currently in clinical development. The purpose of the present study was to examine expression patterns of Bag-1 in a large cohort of breast tumors and to assess the association with Bcl-2, estrogen receptor, progesterone receptor and Her2/neu, and other clinical/pathological variables.     

Metastasis suppression by breast cancer metastasis suppressor 1 involves reduction of phosphoinositide signaling in MDA-MB-435 breast carcinoma cells

Several molecules that suppress metastasis without suppressing tumorigenicity have been identified, but their mechanisms of action have not yet been determined. Many block growth at the secondary site, suggesting involvement in how cells respond to signals from the extracellular milieu. Breast cancer metastasis suppressor 1 (BRMS1)-transfected MDA-MB-435 cells were examined for modifications of phosphoinositide signaling as a potential mechanism for metastasis suppression. 435/BRMS1 cells expressed <10% of phosphatidylinositol-4, 5-bisphosphate compared with parental cells, whereas levels of the PtdIns(4)P and phosphatidylinositol-3-phosphate were unchanged. Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] were decreased in 435/BRMS1 cells by approximately 50%. Phosphatidylinositol-3,4,5-trisphosphate levels were undetectable in 435/BRMS1 cells, even when stimulated by exogenous insulin or platelet-derived growth factor. Immunofluorescence microscopy to examine cellular distribution confirmed that phosphatidylinositol-4,5-bisphosphate distribution with cells was unchanged but was uniformly decreased throughout the cell. Although the gross morphology of 435/BRMS1 cells is similar to the parent, filamentous actin was more readily apparent in 435/BRMS1. Intracellular calcium, measured using Fluo-3 and Fura-2 fluorescent calcium indicator dyes, was somewhat lower, but not statistically different in 435/BRMS1 compared with parental cell. However, when stimulated with platelet-derived growth factor, MDA-MB-435 cells, but not 435/BRMS1 cells mobilized intracellular calcium. Taken together, these results implicate signaling through phosphoinositides in the regulation of breast cancer metastasis, specifically metastasis that can be suppressed by BRMS1.     

淋巴结阴性乳腺癌PAI-Ⅰ表达及预后价值

Objective:To investigate the expressions of plasminogen activator inhibitor type 1(PAI-1),C-erbB-2,VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAJ-1 in node-negative breast cancer,Methods:The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cencer.Expressions of PAI-1,C-erbB-2,VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months(range 22-117 months).Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed.Results:High PAI-1 level was positively associated with high histologic grade of the tumors.Disease-free survival(DFS)was significantly shorter for the patients with moderate to intensive expression of PAI-1 lban for those with negative(X2=25.46,P＜0.001:X2=23.07,P＜0.001)to mild expression(X2=19.75,P＜0.001:X2=17.40.P＜0.001).Although on univariate analysis of the prognostic factors,tumor size,location of primary tumor and age as well as expressions of PAI-1,VEGF and Ki-67 were all significantly prognostic factors for DFS(P＜0.05),PAI-1 was the only independent prognostic factor on multivariate analysis(P＜0.0001;hazard ratio[HR].4.041:95% confidence intewal[CI],1.928-8.468).Conclusion:These results of the current study indicate that intermediate or high expression of PAI-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.     

Expression and prognostic value of EGFR in invasive breast cancer

Epidermal growth factor receptor (EGFR) is a membrane receptor expressed in a variety of solid human cancers and directly related with poor prognosis. The objective of this work was to evaluate the EGFR content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value. EGFR levels were examined by radioligand binding assays in 846 patients with invasive breast cancer. The median follow-up period was 50 months. There was a wide variability of EGFR levels among the studied tumors (0.01-403 fmol/mg protein). Statistical analysis showed that EGFR levels were significantly higher in younger patients (p=0.0001). EGFR were also notably higher in ER-negative or PgR-negative tumors than in ER-positive (p=0.0001) or PgR-positive tumors (p=0.001). In addition, the presence of high intratumoral EGFR levels (cut-off: 6 fmol/mg protein) was associated with both shorter relapse-free survival (p=0.04) and overall survival (p=0.01) in the group of patients as a whole, as well as with overall survival in the subgroup of patients without any type of systemic adjuvant treatment (p=0.02). However, EGFR levels did not achieve significance as independent prognostic factor in the multivariate analysis. There is a wide variability of intratumoral EGFR levels in breast carcinomas, and these protein levels correlated positively with a poor prognosis in the t univariate analysis. However, further studies are necessary in order to assess the possible clinical value of EGFR in combination with other essential components of the EGFR family network.     

JAG1和Notch3在乳腺癌组织中的表达及预后价值

目的探讨JAG1和Notch3在乳腺癌组织中的表达水平及预后意义。方法通过在线Oncomine数据库和Kaplan-Meier Plotter数据库分析JAG1和Notch3在乳腺癌组织中的表达情况及对预后的影响。收集2008年1月至2013年12月乳腺浸润性导管癌组织及配对癌旁组织各80例,采用实时荧光定量PCR(QPCR)和免疫组织化学SP法分别检测JAG1和Notch3的mRNA和蛋白水平,分析JAG1和Notch3蛋白表达与乳腺癌临床病理特征和总生存时间(OS)的关系。多因素分析采用Cox比例风险回归模型。结果 Oncomine数据库分析显示,乳腺癌组织中JAG1和Notch3的mRNA水平均高于癌旁组织(P<0.05)。80例乳腺浸润性导管癌组织中JAG1 mRNA水平为1.58±0.56,高于癌旁组织的1.23±0.48(P=0.0039);乳腺浸润性导管癌组织中Notch3 mRNA水平为2.39±0.83,高于癌旁组织的1.95±0.64(P=0.0036)。JAG1和Notch3蛋白在乳腺癌组织中的高表达率为71.3%(57/80)和80.0%(64/80),分别高于癌旁组织的8.8%(7/80)和11.2%(9/80),差异均有统计学意义(P=0.005,P=0.003). JAG1和Notch3蛋白表达在乳腺癌组织中呈正相关(r=0.267,P=0.017)。JAG1和Notch3表达与乳腺癌淋巴结转移、TNM分期和组织学分级有关(P<0.05)。Kaplan-Meier Plotter在线分析显示, JAG1或Notch3高表达的乳腺癌患者的OS短于低表达者(P>0.05)。80例乳腺浸润性导管癌患者中,JAG1高表达者的中位OS为38.3个月,低于JAG1低表达者的80.4个月(P=0.0394);Notch3高表达者的中位OS为39.3个月,低于Notch3低表达者的80.2个月(P=0.0334),且JAG1和Notch3均高表达者的中位OS最短,为27.3个月。Cox多因素分析显示,淋巴结转移、JAG1表达和Notch3表达是影响乳腺癌患者OS的独立因素(P<0.05)。结论 JAG1和Notch3在乳腺癌组织中高表达,且与预后不良有关,有望成为临床评估乳腺癌预后的潜在生物标志物。     

The prognostic value of the human kallikrein gene 9 (KLK9) in breast cancer

Background. Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some of them are useful diagnostic/prognostic markers. KLK9 is a newly discovered human kallikrein gene that is expressed in several tissues including thymus, spinal cord, testis, prostate, breast, and ovary. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones, mainly estrogens and progestins, in cancer cell lines. Experimental design. We studied the expression of KLK9 by quantitative RT-PCR in 169 breast cancer patients of different stages, grades and histological types. We also compared the relation between KLK9 expression and other clinicopathological variables and patient survival. Results. KLK9 expression is significantly higher in patients with early stage cancers (p = 0.039) and in patients with small tumor size (<2 cm) (p = 0.028). Kaplan-Meier survival curves demonstrated that KLK9-positive patients have longer disease-free and overall survival (p = 0.015 and 0.036, respectively). Univariate and multivariate analysis also indicates that KLK9 expression is associated with increased disease-free and overall survival. When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of disease-free survival in the estrogen receptor (ER) and progesterone receptor (PR) negative subgroups of patients (Hazard Ratio 'HR' = 0.28, and 0.38, respectively, and p = 0.011 and 0.028, respectively). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in these subgroups of patients. Similar results were obtained for overall survival. Conclusions. KLK9 is a new potential independent marker of favorable prognosis in breast cancer.     

The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer

The monoclonal antibodies HMFG1 and HMFG2 identify antigens of the milk fat globule membrane which are also found on breast epithelial cells. Immunohistochemical staining was performed using both antibodies on formalin fixed, paraffin embedded sections of 93 breast carcinoma, 36 histologically benign lesions and 29 histologically normal breast tissue blocks. In both normal and benign breast disease the staining was largely extracellular whilst in malignant tissue the staining was variable and often intracellular. Nine carcinomas did not stain with either antibody. The staining patterns of malignant tissues were graded and no correlation was found between the grades and survival or indices of prognosis, (the oestrogen receptor status, Bloom's grade and the presence or absence of metastases to the axillary nodes.) This study indicates that with the present methods available for grading staining patterns, although of diagnostic value, these monoclonal antibodies are unlikely to assist in determining either the degree of tumour differentiation or prognosis in breast carcinoma.     

乳腺癌转移抑制基因作用机制

乳腺癌转移抑制基因（BRMS1）在人乳腺癌、黑色素瘤、膀胱癌、卵巢癌、嗜铬细胞瘤中具有抑制肿瘤细胞转移的能力，可明显减少转移灶的发生，作用机制复杂多样而又非典型，成为研究抑制肿瘤转移的新靶点。     

乳腺癌转移抑制基因作用机制

乳腺癌转移抑制基因(BRMS1)在人乳腺癌、黑色素瘤、膀胱癌、卵巢癌、嗜铬细胞瘤中具有抑制肿瘤细胞转移的能力,可明显减少转移灶的发生,作用机制复杂多样而又非典型,成为研究抑制肿瘤转移的新靶点。     

New factors of possible prognostic value in breast cancer]

Over the past 10 years, we have witnessed a variety of potential prognostic factors of breast cancer including proliferative rate, ploidy, growth factor receptors, oncogenes and cathepsin D production. Some of these variables seem to predict the prognosis of the patients but the available data are conflicting and call for carefully conducted quality-control studies to analyze intra- and interlaboratory variations. In this review, we provided a framework from which prognostic factor information can be used directly to make treatment decisions.