Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer

BACKGROUND: Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are reliable ways to identify overexpression or amplification of the HER-2/neu (HER2, symbol ERBB2) gene, but each technique requires a high-quality tissue sample, which may not be available. We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to tissue HER2 status in metastatic breast cancer, and we defined an optimal decision-level concentration of serum HER2 for prediction of tissue HER2 status. METHODS: In 195 patients with metastatic breast cancer, we determined HER2 expression by IHC and performed FISH analysis on tumors for which IHC staining was graded as 2+. We measured serum HER2 by immunoassay and used ROC curve analysis to determine optimal serum HER2 ECD concentrations for differentiation between positive and negative HER2 status. RESULTS: IHC results were 0/1+ for 30 (15%) of the patients, 2+ for 89 (46%), and 3+ for 76 (39%). FISH revealed HER2 amplification in 19 (21%) of the IHC 2+ tumors. Mean (SE) serum HER2 ECD was 22.2 (5.1) microg/L in the tissue HER2-negative group, significantly lower than the concentration of 363 (96) microg/L in the tissue HER2-positive group (P<0.0001). ROC curve analysis showed 95% specificity and 62% sensitivity for tissue HER2 positivity at 37 microg/L of serum HER2. CONCLUSION: To use serum HER2 concentration as an alternative to direct determination of tissue HER2 status, we suggest 37 microg/L as a cutoff for predicting positive tissue HER2 with 95% specificity. Sensitivity, however, is low.     

Serum HER2/ECD value in stage I and II early breast cancer �C need of a lower cut-off?

BACKGROUND: HER2 overexpression is well-established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there are no consistent data for patients with early breast cancer. METHODS AND RESULTS: 41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p = 0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. CONCLUSION. Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.     

ELISA方法检测乳腺癌患者血清HER2的临床价值

目的：HER2基因扩增和HER2蛋白过表达是乳腺癌患者预后不良的分子标志,是临床指导靶向HER2治疗的标准。肿瘤细胞中HER2蛋白胞外域经蛋白酶裂解脱落入血,血清中HER2水平改变可以用于监测乳腺癌的进展和治疗疗效。本研究旨在分析血清HER2水平与乳腺癌组织HER2表达状态的相关性,并探讨血清HER2水平与临床病理因素的关系,以评价其潜在的临床应用价值。方法：分别采用ELISA和免疫组化方法检测70例乳腺癌患者血清HER2水平和肿瘤组织HER2表达状态,Spearmen秩相关分析二者的相关性,χ2检验分析血清HER2与临床病理因素的关系。结果：乳腺癌患者血清HER2水平和组织HER2表达呈正相关（r=0．686,P〈0．001）;肿瘤直径大于2cm患者血清HER2水平高于小于等于2cm患者（χ2=9．071,P=0．030）;临床II-III期患者血清HER2水平高于I期患者（χ2=9．001,P=0．030）;ER阴性患者血清HER2水平高于ER阳性患者（χ2=16．307,P〈0．0.001）：PR阴性患者血清HER2水平高于PR阳性患者（χ2=16．164,P〈0．001）,而血清HER2水平在不同患者年龄、组织学分级和淋巴结状态等临床病理因素各组间无统计学差异。结论：乳腺癌患者血清HER2水平可以反应肿瘤组织HER2表达状态,其水平升高提示乳腺癌恶性程度高、预后差,是潜在的乳腺癌预后预测和疗效监测的血清学标志,     

复发转移乳腺癌患者血清HER2水平与组织表达状态的相关性

目的探讨复发转移乳腺癌患者血清HER2水平与组织表达状态间的联系,分析血清HER2检测是否可作为组织HER2检测的补充手段。方法采用酶联免疫吸附试验(ELISA)对72例女性复发转移乳腺癌(组织HER2阳性组30例,组织HER2阴性组42例)和30例健康体检女性(健康对照组)进行血清HER2水平检测,将各组的血清HER2水平进行比较,并与组织HER2表达状态进行对比分析。结果组织HER2阳性组的血清HER2水平显著高于组织HER2阴性组和健康对照组,差异有统计学意义(P<0.0001);组织HER2阴性组血清HER2水平与健康对照组比较差异无统计学意义(P=0.163);组织HER2阳性组有22例血清HER2阳性,阳性符合率为73.4%(22/30),组织HER2阴性组有32例血清HER2阴性,阴性符合率为78.6%(32/42)。血清HER2水平与组织HER2表达状态呈正相关(χ2=21.626,r=0.547)。结论血清HER2水平与组织HER2表达状态呈正相关,且血清HER2可以作为组织HER2检测的补充手段。     

血清肿瘤标记物与HER2阳性乳腺癌骨转移的相关性研究

目的观察人类表皮生长因子受体2(HER2)阳性乳腺癌的肿瘤标记物水平与骨转移的相关性。方法收集确诊为HER2阳性浸润性乳腺癌的100例患者,根据有无骨转移分为2组:骨转移组(n=40),未骨转移组(n=60)。采用ELISA法监测患者入院时、随访发生骨转移时血清糖类抗原(CA153)和癌胚抗原(CEA)水平,观察2组患者年龄、病理分型、血清肿瘤标记物和赫赛汀的应用情况等,比较2组患者上述指标的差异。采用受试者工作特征(ROC)曲线预测血清CA153、CEA对HER2阳性乳腺癌骨转移的价值。结果 HER2阳性乳腺癌患者中,骨转移组和未骨转移组入院时血清CEA、CA153水平差异无统计学意义(P0.05),ROC曲线发现血清CEA水平(AUC 0.72,95%CI0.63~0.81,P=0.01)和CA153水平(AUC 0.67,95%CI 0.60~0.77,P=0.03)为预测预测骨转移的因素。其中CA15317.2U/mL预测HER2阳性乳腺癌患者骨转移的敏感度为78.8%,特异度为45.0%;CEA2.64μg/L预测骨转移的敏感度为75.8%,特异度为43.3%。结论血清CA153和CEA水平对HER2阳性乳腺癌的骨转移有一定的预测价值。     

HER2 Ile655Val polymorphism is negatively associated with breast cancer susceptibility

Background

The HER2 (human epidermal growth factor receptor‐2) Ile655Val (rs1136201) genetic polymorphism can alter the receptor structure and its auto‐activation, which can modify the signal transduction and, consequently, the cell cycle regulation. For this reason, this polymorphism has been extensively investigated as a candidate marker for breast cancer (BC). In this context, the aim of this study was to evaluate the possible influence of HER2 Ile655Val in BC susceptibility and prognostic factors in a Brazilian population.

Methods

Polymorphism genotype was assessed through RFLP‐PCR in 107 BC patients with clinicopathological data available and in 150 women with no evidence of neoplasia and with no familial history of BC as control group. Association between this polymorphism and BC susceptibility and clinical parameters was evaluated through odds ratio (OR) and chi‐squared or Fisher's exact test, respectively.

Results

A significant negative association between valine allele and BC susceptibility in dominant model was found (OR 0.5; 95% CI 0.27‐0.93, P = .036). No significant association was found in relation to BC clinicopathological features (tumor size, lymph nodes commitment, histological grade, HER2 overexpression, hormonal receptors, p53, and Ki‐67).

Conclusion

Although this polymorphism did not demonstrate potential as a prognostic marker, it may be a suitable susceptibility marker for BC.

     

人类表皮生长因子受体2在乳腺癌表达与临床的相关病理特征分析

目的 评估人类表皮生长因子受体2(HER2)预测价值,并分析其与常见的组织病理学参数的相关性。方法 收集陕西省人民医院2011年～2014年之间160例接受手术治疗的乳腺癌患者组织标本,通过免疫组织化学方法(IHC)和荧光原位杂交(FISH)检测 HER2水平,通过χ²检验用来评估HER2基因扩增状况及不同临床病理特性的相关性,临床参数包括:肿瘤大小、组织学分级、雌激素受体(ER)和孕激素受体(PR)表达,年龄、绝经情况和Ki-67指数。结果 HER-2表达与组织学分级、淋巴结转移、ER水平、PR,Ki-67指数差异存在统计学意义(均P<0.05)。相对于HER-2⁺组患者,HER-2^-病变多表现为雌激素ER阴性、孕激素阴性、ER阴性、淋巴结阴性、ki-67≥20%。结论 HER-2表达与多种临床病理因素存在相关性。     

Quantitative analysis of diagnostic guidelines for HER2-status assessment

Human epidermal growth factor receptor 2 (HER2, alias ERBB2)-targeted therapy in breast and gastric cancers depends on the reliable assessment of HER2 protein expression and (in equivocal cases) the quantitative evaluation of HER2 gene amplification. Typically, HER2 and centromere 17 gene copy numbers are evaluated using in situ hybridization (ISH) to calculate ratios for which cutoff values dividing nonamplified and amplified cases have been proposed. Although several studies have investigated how laboratory procedures affect diagnostics, a rigorous quantitative assessment of the diagnostic guidelines for data analysis is still missing. Here, we analyze the dependence of the diagnosed HER2/chromosome 17 ratios on i) sample size (evaluated cells), ii) gene/chromosome signal distributions, and iii) the approach used for quotient calculation using Monte Carlo simulations. Our data show that the current recommendation may lead to statistical HER2/CHR17 ratio variations of up to 0.94 and may therefore lead to incorrect HER2 status diagnoses, given the ratio threshold of 2.0 defined by the Food and Drug Administration. Moreover, borderline cases may receive different amplification diagnoses, depending on the ratio calculation approach: Brightfield-silver ISH with aggregated signal counts may underestimate the HER2/CHR17 ratio compared with two-color fluorescence ISH. Our results provide a basis for quantitative rationales behind HER2 diagnostic guidelines that call for increased numbers of evaluated cells and emphasize the importance of well-designed data analysis methods in diagnostic pathology, especially for predictive clinical application.     

肺癌病人血清MMP-2和MMP-9的检测

目的 :探索肺癌病人循环MMP - 2和MMP - 9的临床意义。方法 :采用ELISA方法 ,检测 6 5例肺癌、4 5例肺炎和 5 0例正常人血清MMP - 2和MMP - 9。结果 :在上述 3种血清样品中 ,MMP - 2平均水平分别为 91.4 5ng/ml,6 8.98ng/ml和10 2 .4 6ng/ml;MMP - 9平均水平分别为 2 5 7.0 1ng/ml,14 9.2 2ng/ml和 110 .6 9ng/ml。正常人和肺癌病人相比较 ,血清MMP - 2平均水平无显著差异 ,MMP - 9的平均水平具有极显著差异 (P <0 .0 1)。正常人和肺炎病人相比较 ,血清MMP - 2的平均水平具有显著差异 ,MMP - 9的平均水平则无显著差异 (P >0 .0 5 )。结论 :循环MMP - 9是诊断肺癌的一个候选标记物。     

The molecular basis for apoptotic defects in patients with CD95 (Fas/Apo-1) mutations

Heterozygous mutations of the receptor CD95 (Fas/Apo-1) are associated with defective lymphocyte apoptosis and a clinical disease characterized by lymphadenopathy, splenomegaly, and systemic autoimmunity. From our cohort of 11 families, we studied eight patients to define the mechanisms responsible for defective CD95-mediated apoptosis. Mutations in and around the death domain of CD95 had a dominant–negative effect that was explained by interference with the recruitment of the signal adapter protein, FADD, to the death domain. The intracellular domain (ICD) mutations were associated with a highly penetrant Canale-Smith syndrome (CSS) phenotype and an autosomal dominant inheritance pattern. In contrast, mutations affecting the CD95 extracellular domain (ECD) resulted in failure of extracellular expression of the mutant protein or impaired binding to CD95 ligand. They did not have a dominant–negative effect. In each of the families with an ECD mutation, only a single individual was affected. These observations were consistent with differing mechanisms of action and modes of inheritance of ICD and ECD mutations, suggesting that individuals with an ECD mutation may require additional defect(s) for expression of CSS.     

Single-chain antibody/activated BID chimeric protein effectively suppresses HER2-positive tumor growth

BH3-interacting domain death agonist (BID) is a crucial element in death signaling pathways and is recognized as an intracellular link connecting the intrinsic mitochondrial apoptotic and extrinsic death receptor-mediated apoptotic pathways. Herein, we describe experiments conducted with a fusion protein, which was generated by fusing a human epidermal growth factor receptor-2 (HER2)-specific single-chain antibody with domain II of Pseudomonas exotoxin A and the truncated active BID (tBID). These experiments extend our previous work on several other immuno-proapoptotic proteins. Specifically, by excluding cells with undetectable HER2, we showed that the secreted immuno-tBID molecule selectively recognized and killed HER2-overexpressing tumor cells in vitro by attacking their mitochondria and inducing their apoptotic death. This apoptosis could only be inhibited partially by caspase pan-inhibitor zVAD and mitochondrial protector TAT-BH4. Subsequently, we transferred the immuno-tbid gene into BALB/c athymic mice bearing HER2-positive tumors together with other immuno-proapoptotic proteins using i.m. injections of liposome-encapsulated vectors. The expression of the immuno-tbid gene suppressed tumor growth and prolonged animal survival significantly. We also shortened the translocation domain of Pseudomonas exotoxin A II to only 10-amino acid sequence, which were crucial for furin cleavage. The new recombinant molecule retained the translocation efficiency and the ability of specific killing HER2-positive tumor cells. Our data showed that, compared with the toxins employed before, the chimeric immuno-tBID molecule can not only specifically recognize HER2-positive tumor cells but also certainly induce apoptosis even in the presence of zVAD and TAT-BH4, thereby suggesting an alternative approach to treating HER2/neu-positive tumors.     

Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis

The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury while its value in lupus nephritis is uncertain. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis.This study included 70 systemic lupus erythematosus (SLE) patients; 50 with active lupus nephritis (LN) and 20 without as well as 20 matched controls. The neutrophil gelatinase-associated lipocalin (NGAL) in both serum and urine samples was measured by enzyme-linked immunosorbent assay (ELISA). Patients with active LN received standard treatment then assessed for response as well as the value of urinary NGAL (uNGAL). Our results revealed that, The SLE patients with or without LN had an elevated urinary NGAL as compared to controls (p?相似文献   

GP和PathVysion HER2试剂盒检测乳腺癌患者HER2基因状态的比较

目的 通过与进口PathVysion HER2试剂盒比较,评价国产金菩嘉GP HER2试剂盒检测乳腺癌患者HER2基因状态的临床应用价值.方法 收集108例乳腺浸润性导管癌(简称"乳腺癌")肿瘤组织标本,分别采用FISH技术与GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者HER2基因表达水平,比较2种试剂盒检测乳腺癌患者HER2基因表达差异,并评价GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性.结果 GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增率分别为25.0%(27/108)和26.9%(29/108).与PathVysion HER2试剂盒相比,GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性分别为89.7%(26/29)、98.7%(78/79)和96.3%(104/108),PPV和NPV均为96.3%(26/27,78/81).GP HER2试剂盒检出第17号染色体多倍体的敏感度、特异度和准确性分别为93.3%(14/15)、100%(93/93)和99.1%(107/108).结论 GPHER2试剂盒在检测乳腺癌患者组织标本中HER2基因状态的敏感度和特异度及准确性高,在临床评价乳腺癌HER2基因状态中具有广泛应用价值.     

GP和PathVysion HER2试剂盒检测乳腺癌患者HER2基因状态的比较

目的 通过与进口PathVysion HER2试剂盒比较,评价国产金菩嘉GP HER2试剂盒检测乳腺癌患者HER2基因状态的临床应用价值.方法 收集108例乳腺浸润性导管癌(简称"乳腺癌")肿瘤组织标本,分别采用FISH技术与GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者HER2基因表达水平,比较2种试剂盒检测乳腺癌患者HER2基因表达差异,并评价GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性.结果 GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增率分别为25.0%(27/108)和26.9%(29/108).与PathVysion HER2试剂盒相比,GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性分别为89.7%(26/29)、98.7%(78/79)和96.3%(104/108),PPV和NPV均为96.3%(26/27,78/81).GP HER2试剂盒检出第17号染色体多倍体的敏感度、特异度和准确性分别为93.3%(14/15)、100%(93/93)和99.1%(107/108).结论 GPHER2试剂盒在检测乳腺癌患者组织标本中HER2基因状态的敏感度和特异度及准确性高,在临床评价乳腺癌HER2基因状态中具有广泛应用价值.

Abstract：

Objective To evaluate clinical application of Jin Pujia GP HER2 probe kit in testing HER2 gene status of breast cancer through comparing it with PathVysion HER2 probe kit. Methods HER2 gene status were detected from 108 cases with invasive ductal breast cancer using GP and PathVysion HER2 probe kits by FISH. HER2 gene expression levels were measured by GP and PathVysion HER2 probe kits, and the sensitivity, the specificity and the accuracy of GP HER2 probe kit were evaluated. Results HER2 gene amplification positive rates detected by GP HER2 probe kit and PathVysion HER2 probe kit were 25.0%(27/108) and 26.9% (29/108), respectively. As compared with PathVysion HER2 probe kit, the sensitivity, the specificity and the accuracy of the GP HER2 kit were 89. 7% (26/29), 98.7% (78/79)and 96. 3% ( 104/108), respectively, whereas the PPV and NPV were 96. 3% (26/27) and 96. 3% (78/81), respectively. The GP HER2 probe kit had a sensitivity of 93.3% ( 14/15), a specificity of 100%(93/93) and an accuracy of 99. 1% (107/108) for detecting polysomy 17. Conclusion GP HER2 probe kit has high sensitivity and specificity for detecting HER2 gene status in breast cancer patients, and it has clinical application value.     

肝病患者外周血血管生成素-2定量检测的临床价值分析

目的 观察肝病患者外周血中血管生成素-2(Ang-2)的表达水平,探讨与肝癌(HCC)发展关系及临床价值.方法 收集不同肝病患者外周血标本,以酶联免疫吸附法(ELISA)检测Ang-2浓度,并分析与血管内皮生长因子(VEGF)相互关系.结果 肝病患者血Ang-2水平,正常对照组为(17.4±2.6)ng/ml、急性肝炎组为(23.5±6.5)ng/ml、慢性肝炎组为(20.9±7.1)ng/ml,肝硬化组为(25.5±5.8)ng/ml和肝癌组为(40.8±3.5)ng/ml;Ang-2水平随肝病进展呈进行性增加,肝癌组明显高于对照组和良性肝病组(P<0.001),且Ang-2与VEGF改变呈显著正相关(r=0.769,P=0.026);如以血Ang-2>35ng/ml为界,肝癌组95%异常,肝硬化组1例异常(2.9%),其他组未见异常,与AFP联检对肝癌具有互补诊断价值.结论 Ang-2过表达与肝癌发展密切相关,且有助于肝癌的诊断与鉴别.     

GP和PathVysion HER2试剂盒检测乳腺癌患者HER2基因状态的比较

目的 通过与进口PathVysion HER2试剂盒比较,评价国产金菩嘉GP HER2试剂盒检测乳腺癌患者HER2基因状态的临床应用价值.方法 收集108例乳腺浸润性导管癌(简称"乳腺癌")肿瘤组织标本,分别采用FISH技术与GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者HER2基因表达水平,比较2种试剂盒检测乳腺癌患者HER2基因表达差异,并评价GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性.结果 GP HER2试剂盒和PathVysion HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增率分别为25.0%(27/108)和26.9%(29/108).与PathVysion HER2试剂盒相比,GP HER2试剂盒检测乳腺癌患者组织标本中HER2基因扩增的敏感度、特异度和准确性分别为89.7%(26/29)、98.7%(78/79)和96.3%(104/108),PPV和NPV均为96.3%(26/27,78/81).GP HER2试剂盒检出第17号染色体多倍体的敏感度、特异度和准确性分别为93.3%(14/15)、100%(93/93)和99.1%(107/108).结论 GPHER2试剂盒在检测乳腺癌患者组织标本中HER2基因状态的敏感度和特异度及准确性高,在临床评价乳腺癌HER2基因状态中具有广泛应用价值.     

中国人群胰腺癌与胃癌HER2/neu基因表达

  目的  探讨胰腺癌与胃癌组织中HER2/neu基因表达状态及其在治疗与评估临床结局中的作用。  方法  应用免疫组织化学和多色荧光原位杂交技术, 检测北京协和医院手术切除的81例胰腺导管癌及癌旁胰腺组织和100例胃癌及癌旁胃组织标本中HER2/neu蛋白表达及基因状态的变化, 分析HER2/neu蛋白表达与基因状态间的关系及其与胰腺癌和胃癌临床病理改变间的关系。  结果  免疫组织化学显示, 81例胰腺癌组织中9例(11.1%)HER2/neu蛋白表达阳性(2+及3+), 100例胃癌组织中13例(13%)HER2/neu蛋白表达阳性(2+及3+); 荧光原位杂交结果显示, 81例胰腺癌组织中15例(18.5%)HER2/neu基因扩增, 100例胃癌组织中11例(11%)HER2/neu基因扩增。胰腺癌HER2/neu基因扩增与淋巴结转移有显著相关性(P=0.001)。胃癌组织中6例HER2/neu蛋白3+病例均显示HER2/neu基因扩增, 且胃癌组织HER2/neu蛋白表达与其基因扩增有显著相关性(P < 0.0001)。无论是癌旁胰腺组织还是癌旁胃组织均未检测到HER2/neu蛋白表达及基因扩增。  结论  胰腺癌组织HER2/neu蛋白表达与基因扩增不一致, 而胃癌组织HER2/neu蛋白表达与基因扩增有显著相关性。HER2/neu基因异常可能在胰腺癌及胃癌的发生发展中起着重要作用, 对胰腺癌及胃癌患者进行HER2/neu基因状态检测可能对其靶向治疗具有一定的指导意义。     

Usefulness of procalcitonin serum level for the discrimination of severe sepsis from sepsis: a multicenter prospective study

Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis.     

Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic breast cancer patients

BACKGROUND: The role of circulating TGF-beta(1) in prognosis of breast cancer (BC) was investigated with an intention to define TGF-beta(1)-dependent high risk and low risk subsets of patients. METHODS: Fifty three BC patients of all clinical stages and 37 healthy donors (HD) were analyzed for plasma TGF-beta(1) by the TbetaRII receptor-based Quantikine TGF-beta(1) ELISA kit. RESULTS: The plasma TGF-beta(1) level of Stage I/II disease (median: 0.94 ng/ml; n=10)) remained close to HD (median: 1.30 ng/ml; n=37; p>0.1). In contrast, Stage III/IV disease (median: 2.34 ng/ml; n=43) exhibited highly significant TGF-beta(1) elevation (p<0.001) relative to HD. Further analysis revealed that TGF-beta(1) increase was predominantly attributed to Stage IV, metastatic disease patients (Q3=4.23 ng/ml) rather than to the group Stage III/IV (Q3=3.58 ng/ml). Using the plasma TGF-beta(1) concentration of 3.00 ng/ml as the cut-off value, two subgroups of patients were formed. Overall 2-year survival of the first subgroup, having elevated plasma TGF-beta(1) (>3.00 ng/ml; n=10), was 10%. This was significantly decreased (p<0.05) compared to 52% survival observed for the second subgroup of patients with plasma TGFbeta(1) values close to HD (<3.00 ng/ml, n=19). CONCLUSION: We have performed a pilot study to determine the relationship between overall survival and TGF-beta(1) concentration in the blood of metastatic breast cancer patients. The survival was significantly reduced in the patients with elevated plasma TGF-beta(1) levels compared to that of the patients with plasma TGF-beta(1) levels close to normal. We propose that plasma TGF-beta(1) concentration may be a new tumour marker attributed to the presence of metastatic BC cells that may be used in selection of metastatic BC patients with poor prognosis.     

人表皮生长因子受体3在乳腺癌组织中的表达及临床意义

目的探讨人表皮生长因子受体(HER)3基因在乳腺癌组织中的表达及其与临床病理学特征和预后的相关性。方法采用免疫组织化学法检测126例乳腺癌组织中HER3的表达,分析其表达与患者年龄、月经情况、TNM分期、肿瘤大小、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)、HER2及预后的关系。结果 (1)乳腺癌组织中HER3的阳性表达率为30.2%。HER3阳性表达在乳腺癌绝经患者中占43.3%,高于未绝经者的18.2%(P0.05);淋巴结转移阳性的乳腺癌患者HER3阳性表达率为40.0%,高于无淋巴结转移患者的21.2%,差异有统计学意义(P0.05);HER2阳性的乳腺癌患者HER3阳性表达率为42.5%,高于HER2阴性者的24.4%,差异有统计学意义(P0.05)。(2)HER3阳性患者的五年无病生存率更低(P0.05)。(3)HER3与HER2均阳性的乳腺癌患者淋巴结转移率较高(P0.05)。结论 HER3的表达可能在乳腺癌的发生和发展过程中起重要作用,并影响其预后,HER3可能成为判断乳腺癌预后的指标及临床治疗的靶点。