Relationship between plasma D-dimer levels and clinicopathologic parameters in resectable colorectal cancer patients

AIM: To assess the clinical significance of the D-dimer levels and the relationship between plasma D-dimer levels and clinicopathologic parameters in operable colorectal cancer patients. METHODS: The plasma levels of D-dimer were measured pre- and postoperatively in 35 patients with colorectal cancer, and 30 healthy subjects served as controls by the method of quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean preoperative plasma levels of D-dimer in the patients with colorectal cancer (1.06+/-0.24 mg/L) were significantly higher than those of controls (0.33+/-0.12 mg/L,P<0.01). The D-dimer levels were remarkably elevated on the 1st day after operation (1.22+/-0.55 mg/L, P<0.01). On the 3rd day the level of D-dimer began to stepwise descend and on the 14(th) day nearly returned to control level. The preoperative levels of D-dimer were significantly correlated with the lymph node metastasis and Dukes stage but had no association with tumor location and the degree of differentiation. A stepwise increase in the mean D-dimer levels was found with increase of the tumor stage. CONCLUSION: Hypercoagulation and higher fibrinolytic activities occur in patients with colorectal cancer. The operative trauma could enhance the fibrinolysis in the patients with colorectal cancer. The measurement of preoperative D-dimer levels is considered to be useful for predicting lymph node metastasis and stage of colorectal cancer.     

非小细胞肺癌患者血浆Cripto-1的水平及临床意义

目的探讨非小细胞肺癌患者(NSCLC)血浆中CR-1的表达水平与患者临床病理特征之间的关系,及其对肺癌预后的判断价值。方法收集35例正常人血浆,40例良性肺部疾病患者和102例NSCLC患者血浆,用酶联免疫吸附法(ELISA)检测血浆CR-1表达水平。结果NSCLC患者血浆CR-1水平远高于健康对照组(P<0.05),良性肺部疾病患者血浆CR-1浓度虽也有一定的升高,但较之肺癌组低,二者间差异有显著性(P<0.05)。肺癌患者血浆CR-1水平与淋巴结转移状态和临床分期有关(P<0.01)。血浆CR-1与患者生存期密切相关,生存>12个月患者血浆CR-1明显低于<12个月者(P<0.01)。结论血浆CR-1与NSCLC的病程进展及生存期相关,是一种有价值的预后判断指标。     

Measurement of thrombus precursor protein in septic patients with disseminated intravascular coagulation and liver disease

BACKGROUND AND OBJECTIVES: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to the widespread deposition of fibrin in the circulation. Therefore, the determination of soluble fibrin is crucial for the diagnosis of DIC. Thrombus precursor protein (TpP) levels can be determined as a measure of soluble polymers, which are the immediate precursors of insoluble fibrin. In this study, the potential diagnostic usefulness of this TpP test was investigated in septic patients with DIC and liver diseases. DESIGN AND METHODS: TpP analysis was performed on 155 plasma samples from 95 septic patients, including 72 patients without liver disease and 23 patients with liver diseases, and on 42 plasma samples from normal healthy subjects. The study population was subdivided according to three phases of DIC described as compensated, decompensated and full-blown DIC. Plasma TpP level was determined using a new assay, the TpPTM (American Biogenetic Sciences, USA), which is based on an ELISA method. RESULTS. Septic patients with decompensated (16.1 9.1 mg/mL) or full- blown (20.9 12.4 mg/mL) phases of DIC had significantly higher TpP levels than those with the compensated (5.6 6.2 mg/mL) phase of DIC or healthy controls (2.9 1.6 mg/mL). In septic patients with liver disease, a significant difference was found between the TpP levels of patients with full- blown DIC (21.6 10.6 mg/mL) and those of patients with the decompensated phase (13.4 6.5 mg/mL). Plasma TpP levels correlated significantly with other DIC parameters including platelet count, fibrinogen, antithrombin and TAT, and correlated weakly with D-dimer. INTERPRETATION AND CONCLUSIONS: Our findings indicate that septic patients who developed decompensated or full-blown DIC or organ dysfunction have significantly higher plasma levels of TpP, and suggest the potential usefulness of the TpP assay as an aid to the diagnosis of DIC in cases of sepsis and liver disease complicated by sepsis.     

结肠癌患者外周血VEGF-C和CK20 mRNA的表达与淋巴转移的关系

目的探讨结肠癌患者外周血VEGF-C mRNA和CK20 mRNA的表达与淋巴转移的关系。方法应用RT-PCR检测80例结肠癌患者、30例结肠良性肿瘤患者、30例健康人外周血VEGF-C mRNA和CK20 mRNA的表达。结果 VEGF-C mRNA在结肠癌患者外周血的阳性表达率为52.5%,在结肠良性肿瘤、健康人的表达率分别为10.0%、0,其中有淋巴结转移的结肠癌患者的阳性表达明显高于无淋巴结转移的阳性表达(P<0.05)。CK20 mRNA在结肠癌患者外周血的阳性表达率为60.0%,在结肠良性肿瘤、健康人的表达率均为0,其中有淋巴结转移的结肠癌患者的阳性表达明显高于无淋巴结转移的阳性表达(P<0.05)。结论结肠癌患者外周血VEGF-C mRNA和CK20 mRNA的表达与淋巴转移相关。     

血浆长链非编码RNA H 19在肺癌中的表达及临床意义

目的：探讨长链非编码 RNA (lncRNA) H 19在肺癌患者血浆中的表达水平及其在肺癌诊断中的应用价值。方法收集2015年1月至2015年12月淮安市第一人民医院呼吸内科、放疗科收治的137例肺癌患者,90例肺良性病变,60例健康体检人群作为研究人群。通过荧光定量 PCR 检测 lncRNA H 19在上述人群血浆中的表达水平,统计分析肺癌血浆 lncRNA H 19表达水平与临床病理资料之间的关系,受试者特征(ROC)曲线和曲线下面积(AUC)评估血浆 lncRNA H19单独或与癌胚抗原(CEA)、鳞状细胞癌抗原(SCCA)和神经特异性烯醇化酶(NSE)联合诊断肺癌效能。结果肿瘤组患者血浆 lncRNA H19表达水平显著高于良性病变组(U =1525,P <0.001)及健康对照组(U=570,P<0.001),差异均有统计学意义,血浆lncRNA H19的表达水平与肿瘤大小(χ2=6.177,P=0.017)、淋巴结转移(χ2=5.579,P=0.024)密切相关。lncRNA H19、CEA、SCCA、NSE诊断肺癌的 AUC 分别为0.895、0.818、0.759、0.703。lncRNA H19与 CEA 联合,诊断肺癌AUC增加至0.949,敏感性为82.48%,特异性为94.67%,较CEA单独诊断有显著提高。结论肺癌患者血浆 lncRNA H 19水平显著高于肺良性病变患者及健康对照人群,与临床病理学特征相关,在肺癌诊断中具有一定价值,可辅助传统肿瘤标志物用于肺癌诊断及病情评估。     

Increased soluble CD44 concentrations are associated with larger tumor size and lymph node metastasis in breast cancer patients

Purpose  CD44 is a cell surface glycoprotein involved in cell–cell and cell–substrate interactions, which may be shed or released into circulation by proteolytic enzymatic mechanisms. Alternative splicing of CD44 and aberrant levels of soluble CD44 variants in the serum of cancer patients have been correlated to tumor progression and metastasis in different tumors including breast cancer. In this study we evaluated the clinical value of CD44 serum levels (sCD44) in patients with primary breast cancer. Methods  Concentrations of soluble isoforms sCD44std, sCD44v5 and sCD44v6 were determined with a sensitive ELISA and normalized against the total protein concentration (TP). Pre-operative serum samples from 82 patients and 67 age-matched healthy blood donors were analyzed. The results were correlated to clinico-pathological parameters (tumor size, grading, lymph node metastasis, etc.). Results  In sera of breast cancer patients, we detected elevated concentrations of sCD44v6 (P = 0.0001) and total protein TP (P = 0.0001) in comparison to healthy controls, whereas overall sCD44 (sCD44std) and sCD44v5 did not differ. Patients with sCD44v6-concentrations above the 75%-percentile showed an increased T stage (2.9 cm vs. 1.8 cm) as well as a higher risk for lymph node metastasis (55% vs. 35%). In breast cancer patients with lymph node metastasis the median value of sCD44v6 was significantly higher (P = 0.025) in comparison to patients without lymph node metastasis and healthy controls. Conclusions  Our data suggest an upregulated expression of alternatively spliced soluble CD44 isoforms in breast cancer patients. The specific alterations of certain CD44 isoform concentrations (especially sCD44v6) may reflect disturbances of the nuclear splicing machinery in tumor cells. The clinical significance of our findings are underlined by the positive correlation of elevated sCD44v6 concentrations and lymph node metastases (r _s = 0.25).     

血浆D-二聚体和纤维蛋白原改变在肺癌中的临床意义

目的探讨肺癌患者血浆D-二聚体和纤维蛋白原水平的变化及临床意义。方法测定80例肺癌患者（肺癌组）及46例健康体验者（对照组）血浆D-二聚体、纤维蛋白原水平并进行对比分析。结果肺癌组血浆D-二聚体、纤维蛋白原水平高于对照组（P〈0.05）。肺癌组血浆D-二聚体、纤维蛋白原与病理类型、TNM分期之间无明显关系。治疗缓解组较初治组和复发难治组纤维蛋白原和D-二聚体水平均有下降（P〈0.05）。结论检测肺癌患者血浆D-二聚体及纤维蛋白原水平,可用作判断其体内高凝和纤溶状态,预测其血栓发生的危险程度,估计病情发展状况的依据。     

Clinical significance of plasma D-dimer levels and serum VEGF levels in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Angiogenesis and coagulation system activation are associated with tumor growth and metastasis. Vascular endothelial growth factor (VEGF) has been reported to play a major role in tumor angiogenesis. The elevation of plasma D-dimer level indicates the activation of coagulation and fibrinolysis. The purpose of this study was to: (a) evaluate the correlation between serum VEGF and plasma D-dimer level; (b) analyze the clinical features that might affect the VEGF and D-dimer levels in patients with hepatocellular carcinoma. METHODOLOGY: Twenty patients with hepatocellular carcinoma were included prior to treatment. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma D-dimer levels were measured by quantitative latex microparticle enhanced turbidimetric immunoassay. RESULTS: The presence of a high plasma D-dimer level was found to be correlated with the presence of central necrosis, higher Child's grade, advanced TNM stage, and the presence of portal vein thrombosis when plasma D-dimer levels were compared between different clinicopathologic groups. Tumors larger than 2 cm in diameter had higher median serum VEGF levels than tumors less than 2cm in diameter. No correlation was found between plasma D-dimer level and serum VEGF level in hepatocellular carcinoma patients (r=0.126, p=0.598). CONCLUSIONS: No correlation was found between the plasma D-dimer level and the serum VEGF level in hepatocellular carcinoma patients. The plasma D-dimer level appeared to reflect the tumor stage and vascular invasion of hepatocellular carcinoma. Serum VEGF level in hepatocellular carcinoma patients showed a positive correlation with tumor size.     

Alterations to the fibrinolytic enzyme system in patients with non-small cell lung carcinoma.

Although fibrinolysis has been implicated in the progression and metastasis of lung cancer, no detailed study has been carried out on components measured in samples from both plasma and tumour. This study thus provides the first comprehensive data obtained from 166 patients diagnosed with non-small cell lung carcinoma. Plasma samples were obtained at diagnosis and tumour samples during surgical resection. Appropriate control samples were obtained from normal subjects and patients with chronic obstructive airways disease (plasma) and from organ donors (normal lung tissue). Assays were performed on plasma and tissue extracts for tissue plasminogen activator, urokinase-like activator and plasminogen activator inhibitor (activity and antigen in all cases), together with plasmin-antiplasmin complex, soluble fibrin, D-dimer and thrombin-antithrombin complex. Levels of D-dimer, thrombin-antithrombin complex and plasmin-antiplasmin complex were all significantly higher in plasma from patients, whereas urokinase-like activator activity was reduced. Only two parameters were significantly altered in both the core and periphery of tumour tissue: levels of D-dimer were increased and tissue-type plasminogen activator activity was reduced. Interestingly, significant differences in levels of other fibrinolytic parameters were detected in the core and periphery of tumours. Significant activation of fibrinolysis was indicated in patients, although the origin of this could not be related consistently to changes in levels of plasminogen activator and inhibitor.     

D-二聚体、纤维蛋白原与肺癌的分期及预后的关系研究

目的分析血浆D-二聚体、纤维蛋白原（fibrinogen,FIB）与肺癌的分期、体力状况评分及预后的关系。方法按分期、有无胸水及远处转移、卡氏及ECOG评分、死亡与否对肺癌患者进行分组,分别测定血浆D-二聚体、FIB水平,分析其在不同分组间的差异。结果 D-二聚体水平在以上不同分组间比较均差异显著。FIB水平在死亡组、存活组及不同卡氏及ECOG评分组间比较差异显著,而在其他分组间比较差异均无统计学意义。结论肺癌患者血浆D-二聚体、FIB水平均与预后相关。D-二聚体是比FIB更敏感的反映肺癌高凝状态的指标。     

Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor.

Abnormal platelet activation and an increased risk of thrombosis are frequent findings in cancer. As soluble adhesion molecule P-selectin is being increasingly recognized as reflecting increased platelet activation, we hypothesized raised levels in patients with cancer, obtaining plasma from 24 patients with a cross-section of haematological cancers, 41 with breast cancer, and from an equal number of healthy controls for each patient group. Levels of soluble P-selectin were compared with those of von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity, fibrinolysis and coagulation, respectively). We found raised soluble P-selectin, fibrinogen and vWf in both patient groups compared with their controls (P < 0.01). vWf and soluble P-selectin were higher in the haematological cancers than in breast cancer patients (by 30 and 74%, respectively; both P < 0.01). There was no significant difference in levels of PAI-1 between any group. There were no differences in soluble P-selectin or vWf when the data from the women with breast cancer were classified according to tumour size, lymph node involvement or presence of vascular invasion. We conclude that the platelet marker soluble P-selectin is raised in both haematological and breast cancer, and is higher in the former, but is unrelated to the type or stage of breast cancer.     

Serum and tissue expression of activin a in postmenopausal women with breast cancer

Activins are growth factors involved in the control of cell proliferation and differentiation. Human breast tissues express immunoreactive activin subunits, and activin A is able to inhibit the replication of mammary cells in vitro. The aim of the present study was to evaluate 1) whether breast cancer expresses activin betaA subunit mRNA, 2) whether serum activin A levels are altered in postmenopausal women with breast cancer, and 3) how circulating activin A levels change after tumor removal. Four groups of women (n = 158) were enrolled for the present prospective study: two groups were composed of postmenopausal women with breast cancer (n = 74) or benign lesions (n = 15); the third was a control group composed of healthy postmenopausal women (n = 62); and the fourth group included healthy fertile women (n = 7) undergoing plastic surgery with removal of non-neoplastic mammary tissue. RT-PCR showed that betaA subunit mRNA was expressed in breast carcinoma, fibroadenoma, and normal mammary tissue, and the level of expression was higher in carcinoma than in normal tissue (P < 0.05). Dimeric activin A was detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic tissue (P < 0.01). In women with breast cancer, median serum activin A levels were significantly higher than in controls (P < 0.001). The high serum activin A levels in patients with breast cancer were not correlated with the presence of lymph node metastasis, tumor grade, or tumor diameter. After tumor excision, a significant decrease of activin A in the first and second postoperative days was observed (P < 0.01; Friedman's ANOVA). Conversely, activin A levels remained unchanged after plastic surgery in healthy women. The present results suggest that activin A is expressed and secreted in postmenopausal women with breast cancer. The pathophysiological and possible clinical implications of this finding remain to be investigated.     

乳腺癌组织中nm23、PS2蛋白的表达及临床意义

目的探讨乳腺癌组织中的nm23蛋白、PS2蛋白表达及其临床意义。方法采用免疫组化SP法检测63例乳腺癌组织与56例乳腺良性疾病组织中的nm23蛋白、PS2蛋白,分析nm23蛋白与PS2蛋白表达与患者年龄、组织学分级、临床分期、腋窝淋巴结转移、ER表达及预后的关系。结果nm23蛋白在乳腺癌组织中表达阳性率为76．19％（48／63）,与患者年龄无相关性（P〉0．05）,与组织学分级、临床分期、淋巴结转移及ER相关（P均〈0．05）。PS2蛋白在乳腺癌组织中表达阳性率为66．67％（42／63）,与临床分期无相关性（P〉0．05）,与年龄、组织学分级、淋巴结转移及ER表达相关。nm23蛋白和PS2蛋白在乳腺良性疾病中的表达均高于在乳腺癌组织中的表达水平。nm23蛋白与PS2蛋白均阳性的乳腺癌患者预后明显优于均阴性的乳腺癌患者（P〈0．05）。结论nm23蛋白、PS2蛋白可以作为预测乳腺癌预后的指标。     

非小细胞肺癌患者血清Dickkopf-1水平及其临床意义

目的探讨非小细胞肺癌(NSCLC)患者血清Dickkopf-1(DKK-1)水平及其临床意义。方法采用夹心酶联免疫吸附法(ELISA)法测定102例NSCLC患者和40例肺部良性肺部疾病患者血清DKK-1水平,并以35例正常人血清作为对照,分析DKK-1与肺癌临床特征及预后的关系。结果 NSCLC患者血清DKK-1水平明显高于良性肺部疾病患者和正常对照组(P<0.01),以19.8 ng/ml为临界值,DKK-1对NSCLC诊断灵敏度为84.3%,特异度为80.3%。TNM分期Ⅲ-Ⅳ期患者血清DKK-1水平明显高于Ⅰ-Ⅱ期患者(P<0.01);有淋巴结转移患者高于无淋巴结转移的患者(P<0.01);手术前患者高于手术后患者(P<0.01);复发后病人明显高于复发前患者(P<0.01);存活期3年以上病人明显低于存活期3年以内病人(P<0.01)。结论血清DKK-1水平能够反映疾病的严重程度,可用于判定手术效果、监测复发和评估预后。     

乳腺癌患者血清VEGF含量测定及临床意义

血管内皮生长因子 (VEGF)在肿瘤血管的形成中起到非常重要的作用。本研究采用 EL ISA法检测 36例乳腺癌患者术前血清血管内皮生长因子 (VEGF)含量 ,与良性对照组及正常对照组比较 ,并观察 VEGF与临床病理指标的关系。认为乳腺癌组与良性对照组和正常对照组比较有非常显著差异 ,并与临床分期及淋巴结转移有相关性。     

Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer

OBJECTIVE: Vascular endothelial growth factor (VEGF), a potent angiogenic peptide, and matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme, are found to be abundantly expressed in several types of cancer and correlate with tumour progression. In this study, we investigated the relationship between preoperative plasma VEGF, MMP-9 levels and disease stages in papillary thyroid cancer. DESIGN: Plasma samples were consecutively collected from 30 patients with papillary thyroid cancer preoperatively (seven males and 23 females with a mean age of 45 +/- 16 years) and control plasmas obtained from 30 patients with benign goitre (seven males and 23 females with a mean age of 44 +/- 18 years) and 23 healthy persons (four males and 19 females with a mean age 44 +/- 15 years). Plasma VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay. Cancer progression was staged by the TNM classification of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). RESULTS: In thyroid cancer patients, the plasma VEGF and MMP-9 values were higher than those in controls (51.8 +/- 11.5 ng/l vs. 27.0 +/- 0.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 22.1 +/- 3.0 micro g/l, respectively; P < 0.05), and those in benign goitre (51.8 +/- 11.5 ng/l vs. 39.7 +/- 8.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 23.0 +/- 2.2 micro g/l, respectively; P < 0.05). But, there was no difference of plasma VEGF and MMP-9 between patients with goitre and normal subjects. A comparison of VEGF and MMP-9 levels in patients at each cancer stage and in patients with benign nodule found that plasma VEGF and MMP-9 values in TNM stages III and IV, but not stage I or II, were significantly elevated (P < 0.05). When cancer patients were grouped according to clinopathological features, the plasma VEGF and MMP-9 concentrations were both significantly elevated in patients with large tumour size (P < 0.01), lymph node involvement (P < 0.01), extrathyroidal invasion (P < 0.05), distant metastasis (P < 0.05) or advanced stages (P < 0.01). CONCLUSION: Our study demonstrated that circulating VEGF and MMP-9 levels correlated with progression of papillary thyroid cancer, suggesting plasma VEGF and MMP-9 may serve as preoperative adjuvant markers for assessing disease activity in papillary thyroid cancer. However, they should not be used as a diagnostic tool for differentiating malignant from benign thyroid disorders.     

急性胰腺炎病人血浆血栓调节蛋白、D-二聚体变化的研究

目的探讨急性胰腺炎不同阶段血浆血栓调节蛋白（TM）、D-二聚体的变化及其临床意义。方法采用酶联免疫吸附测定法,分析轻症急性胰腺炎患者（20例）、重症急性胰腺炎患者（16例）、正常对照组（15例）的TM、D-二聚体指标,并做APACHEⅡ评分。结果重症急性胰腺炎患者TM、D-二聚体含量升高,与轻症和正常对照组比较差异有显著性（P〈0．05）。伴随APACHEⅡ评分升高,TM、D-二聚体的含量升高。结论急性胰腺炎病人均存在不同程度的血管内皮细胞损伤及凝血和纤溶系统的激活,血浆TM、D-二聚体含量可作为急性胰腺炎病情进展、预后判定的指标之一。     

Coagulation indicators in chronic stable effort angina and unstable angina: relationship with acute phase reactants and clinical outcome.

The aim of the study was to evaluate which pattern of coagulation indicators characterizes unstable angina and, particularly, its relationship with short-term prognosis. Forty patients with unstable angina (UA Group) at admission in the intensive care unit, 40 patients with chronic stable effort angina (SEA Group), and 20 age- and sex-matched healthy controls were studied. Blood coagulation indicators were fibrinogen, prothrombin fragment F1 + 2 (F1 + 2), thrombus precursor protein (TpP), and D-dimer. C reactive protein (CRP) and cardiac Troponin I (cTnI) have also been determined and compared. Patients in the UA Group were followed for in-hospital adverse events (sudden death, acute myocardial infarction and angina refractory to medical therapy). CRP, D-dimer and cTnI plasma levels were significantly lower in the SEA Group than in the UA Group; the same trend was found for fibrinogen and F1 + 2 plasma levels, although not statistically significant. The TpP was similar in all groups. The control group showed the lowest levels for all indicators. Within the UA Group, 17 patients developed adverse events during hospitalization; F1 + 2, D-dimer, cTnI and CRP plasma levels were higher in these patients than in those with good outcome. Relative risks for adverse events associated with the highest tertile of D-dimer, cTnI, and CRP plasma levels were 8.4 (95% confidence interval, 1.5-48.9), 6.7 (95% confidence interval, 1.1-38.6) and 5.2 (95% confidence interval, 1.1-25.2), respectively. D-Dimer is significantly increased in patients with unstable angina and, in particular, in those who develop an adverse event.     

Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism

The present study was conducted to clarify the predictive and prognostic significance of serum TGF-I(2)1 in breast cancer in relation to Ile655Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2). In a case-control study, 56 consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of TGF-I(2)1 were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using PCR-RFLP method. Serum levels of TGF-I(2)1 were significantly increased in breast cancer patients compared to healthy controls (p<0.001). For the evaluation of the diagnostic significance of serum TGF-I(2)1 the area under the receiver operating characteristic (ROC) curve (AUC) was 0.804, while the optimal cut-off point of 30.86 ng/ml was determined to classify breast cancer patients, which yielded sensitivity of 77%, specificity of 78% and accuracy of 77%. Significantly elevated serum TGF-I(2)1 levels were associated with advanced stages (p=0.023), positive lymph nodes (p=0.019) and postmenopausal status (p=0.031). A marginal trend towards higher TGF-I(2)1 levels was found among patients with Val-containing genotypes compared to homozygous Ile-Ile (p=0.094). In multivariate analysis lymph node metastases (p=0.009) remained the only significant independent determinant of high TGF-I(2)1 levels. With regard to prognostic significance for advanced stages (AUC, 0.704) and lymph node metastasis (AUC, 0.683), when the optimal cut-off value was set at 65.15 pg/ml, the sensitivity was 86% and 67%, the specificity was 60% and 62% and accuracy was 66% and 64%, respectively. Survival was shorter in patients with increased serum TGF-I(2)1 (36 months vs 46 months, p=0.022). Multivariate analysis demonstrated a marginal prognostic significance of serum TGF-I(2)1 for survival (p=0.072). The combination of high TGF-I(2)1 and Val-Val genotype predicts a worse prognosis than high serum TGF-I(2)1 alone. Our findings suggest that serum TGF-I(2)1 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for evaluation, the extension and the outcome of the disease. They also provide clinical evidence for a significant association between HER-2 Ile655Val SNP and serum TGF-I(2)1, resulting to more aggressive phenotype of the tumor and poor prognosis.