The prognostic value of immunoperoxidase staining with monoclonal antibodies NCRC-11 and 3E1.2 in breast cancer

The variation in survival of women with clinically similar breast cancers may lead to difficulty in clinical management so it is important to recognise factors which indicate the prognosis. Immunoperoxidase staining patterns of primary breast tumours using monoclonal antibody NCRC-11 have been shown to relate to overall survival (Ellis et al., 1985) but the results have not been reproducible in other centres. In this study paraffin sections of 483 primary breast cancers were stained with NCRC-11 and 3E1.2 using an immunoperoxidase system. The tumour staining patterns were compared with overall survival using life tables and tested for relative prognostic significance by Cox's multivariate analysis. NCRC-11 related to survival in all 483 cases (chi 2 5.8, P = 0.02) but both antibodies achieved maximum prognostic significance in lymph node negative patients (chi 2 9.4, P less than 0.002 and chi 2 10.7, P less than 0.001) in whom no other factor was more significant. Immunoperoxidase staining patterns produced by monoclonal antibodies NCRC-11 and 3E1.2 are important prognostic factors in breast cancer.     

A new immunoassay using monoclonal antibodies HMFG1 and HMFG2 together with an existing marker CA125 for the serological detection and management of epithelial ovarian cancer

A new method with a low pH step to dissociate serum complexes has been developed to measure serum levels of antigens associated with ovarian cancer. The antigens are detected by monoclonal antibodies HMFG1 and HMFG2 and have been compared to an existing ovarian cancer associated antigen detected by the antibody CA125. Elevated HMFG1 was found in 56%, and elevated HMFG2 in 65% of 924 sera from 85 patients with ovarian cancer. CA125 was elevated in 85% of these sera. When the three markers were used in conjunction, 95% of sera from patients with ovarian cancer were positive--compared with 7% in sera from healthy control subjects. Therefore, the combination of HMFG1, HMFG2 and CA125 increases the diagnostic accuracy. If all three markers are normal in a patient previously treated for ovarian cancer then no further positive information regarding disease status can be obtained by ultrasound and CT scanning.     

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   

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.     

Evaluating the expression and prognostic value of TRAIL-R1 and TRAIL-R2 in breast cancer.

PURPOSE: The cell surface receptors tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 transmit apoptotic signals, and agents that activate these receptors are in clinical development. We sought to determine the expression and prognostic value of TRAIL-R1 and TRAIL-R2 in early-stage breast cancer. EXPERIMENTAL DESIGN: Tissue microarrays containing specimens from 655 breast cancer patients with 20-year follow-up were employed and evaluated with our automated quantitative analysis (AQUA) system. The system uses cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and measures intensity of TRAIL receptor expression using Cy5 conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathologic variables. TRAIL-R1 and TRAIL-R2 expression were similarly studied on 95 unmatched normal breast specimens. RESULTS: TRAIL-R1 expression was not associated with survival. High TRAIL-R2 expression strongly correlated with decreased survival (P = 0.0005). On multivariate analysis, high TRAIL-R2 expression remained an independent prognostic marker, as did nodal status and tumor size. High TRAIL-R2 expression correlated strongly with lymph node involvement (P = 0.0003). TRAIL-R2 expression was stronger in malignant specimens than in normal breast epithelium (P < 0.0001). CONCLUSIONS: High TRAIL-R2 expression was independently associated with decreased survival in breast cancer. The biological basis and the sensitivity of high TRAIL-R2 expressing cells to TRAIL agonists and/or chemotherapy are subject to further investigation. Evaluation of TRAIL-R2 expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted adjuvant treatment. Clinical trials involving TRAIL-R2 agonists should stratify patients based on TRAIL-R2 expression.     

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.     

Favorable prognostic value of SOCS2 and IGF-I in breast cancer

Background  

Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer.     

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.     

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.

     

The prognostic value of apoptotic and proliferative markers in breast cancer

Increasing ability of early breast cancer (BC) diagnosis leading to more early stage detection, better survival, and low relapse marks one of the milestones achieved over the decades. Foregoing poses a challenge for clinicians regarding optimal treatment, in which over- and under-treatment should be avoided. Classical prognostic and predictive factors fall short for individualized adjuvant therapy selection in this patient group. The key to better characterization may be found in the biology underlying individual tumors. We hypothesized that markers related to cellular proliferation and apoptosis and the balance between these two processes in tumor development will be predictive for clinical outcome. Our study population (N = 822) consisted of all early stage BC patients primarily treated with surgery in our center between 1985 and 1996. Sections of available tumor tissue (87 %, 714/822) were immunohistochemically stained for expression of p53, active-caspase-3, and Ki67. In 43 % (304/714) and 18 % (126/714) of this cohort, respectively, a biochemical C2P^® risk prediction and caspase-3 assay were performed. Expression data of the mentioned markers, single, or combined, were analyzed. Results showed that both the single and combined markers, whether of apoptotic or proliferative origin had associations with clinical outcome. An additive effect was seen for the hazard ratios when data on p53, active caspase-3, and Ki67 status were combined. The assembled prognostic apoptotic–proliferative subtype showed significant association for both the overall survival (p = 0.024) and relapse-free period (p = 0.001) in the multivariate analyses of grade I breast tumors. Combined markers of tumor cell apoptosis and proliferation represent tumor aggressiveness. The apoptotic–proliferative subtypes that we present in this study represent a clinical prognostic profile with solid underlying biological rationale and pose a promising method for accurate identification of grade I BC patients in need of an aggressive therapeutic approach, thus contributing to precision medicine in BC disease.     

The prognostic value of androgen receptors in breast cancer subtypes

Introduction

We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype.

Materials and methods

Normal breast parenchyma?≥?5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44⁺CD49f⁺CD133/2⁺ mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples.

Results

8 of 8 IBC samples expressed isolated CD44⁺CD49f⁺CD133/2⁺ stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p?=?0.001). Similarly, the median number of CD44⁺CD49f⁺CD133/2⁺ cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p?=?0.007). 7 of 8 IBC samples expressed CD68?+?histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p?=?0.001). In the validation cohort, the median number of CD68?+?cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p?=?0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p?=?0.02) and with a 79-gene IBC signature (p?<?0.001).

Conclusions

Normal tissue from IBC patients is enriched for both mammary stem cells and macrophages and has higher association with both a tumorigenic stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

     

The prognostic value of tumour-stroma ratio in triple-negative breast cancer

Background

Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression.

Objective

To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer.

Methods

One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥50% stroma were classified as stroma-high.

Results

Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07–5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08–8.32; 0.034).

Conclusion

TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies.     

Bmi-1与乳腺癌发生、发展及预后的相关性研究

目的 研究Bmi-1在乳腺癌发生、发展中的作用及其预后价值.方法 采用免疫组化En Vision法检测38例正常和普通增生乳腺组织、41例不典型增生乳腺组织、33例乳腺原位癌及129例乳腺癌组织中Bmi-1的表达情况,对Bmi-1与乳腺癌的临床分期、腋窝淋巴结转移、激素受体、HER-2、月经、病理类型、无病生存时间以及...     

Circulating tumor-associated antigen detected by the monoclonal antibody HMFG2 in human epithelial ovarian cancer

A radioimmunometric sandwich assay for the tumour-associated antigen defined by the monoclonal antibody (MAb) HMFG2, has been used to measure serum levels of the antigen in 76 healthy controls, 38 ovarian carcinoma patients pre-operatively, 98 patients 2 to 6 weeks after surgery and 36 patients at relapse or in complete remission at 12 months. HMFG2 antigen levels were elevated in 33% of stage-I and 62% of II-IV patients pre-operatively; they reflected bulk of disease post-surgically and were significantly higher in patients in relapse than in those who were in complete remission. HMFG2 antigen levels predicted the clinical course of disease in the majority of patients.     

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.     

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.