Efficiency of composite laboratory tests in the diagnosis of liver malignancies

The utility of the markers CEA, beta-HCG, CA-50, alpha-fetoprotein (APF), ferritin, alkaline phosphatase (AP), its isoenzyme liver-1 (APL1), gamma-glutamyltransferase (gGT), its fast migrating isoenzyme (gGT1) and 5'nucleotidase (5'N) in differentiating liver malignancies and benign involvement was evaluated in the sera of 85 patients with hepatocellular carcinoma (HCC), 157 with chronic liver disease (CLD) and 91 with liver metastases (LM) derived from different tumors. The mean concentrations of all the parameters except CEA and GGT1 were significantly different in HCC and CLD, but a broad overlap existed in the two groups, so different cut-offs were considered to assess the positive and negative predictive values and test efficiency (Eff). The best results were observed considering AFP greater than 100 IU/m (Eff0.86), ferritin greater than 800 ng/ml (Eff0.69), CA-50 greater than 100 U/ml (Eff 0.63), beta-HCG greater than 10 mU/ml (Eff 0.61), AP greater than 300 IU/ml (Eff 0.66), the presence of APL1 (Eff 0.78), 5'N greater than 25 mU/ml (Eff 0.70), gGT greater than 100 mIU/ml (Eff 0.63). Among HCC patients 17% did not secrete AFP; in 26% the protein was less than 100 IU/ml and in 36% less than 400 IU/ml. Apart from AFP the most effective marker was APL1. At the above cut-offs more than three parameters were simultaneously positive in 71% of HCC and 9.9% of CLD. CEA, CA50, AFP were the only parameters that distinguished the HCC from the LM group; in the latter, APL1 was also a very sensitive marker (87%) for neoplastic involvement of the liver.     

Pattern analysis of serum alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma in liver cirrhosis

In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.     

Improvement of liver cancer detection with simultaneous assessment of circulating levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes

We assessed the presence of alpha-fetoprotein (AFP) complexed with IgM (AFP-IgM IC) in serum of patients affected by hepatocellular carcinoma (HCC), cirrhosis and chronic hepatitis as well as in healthy subjects by means of a dedicated ELISA assay. The amount of AFP-IgM IC was expressed in arbitrary units (AU) on a reference standard curve. Free AFP (FAFP) levels were determined in parallel in each sample by means of an automated immunoassay system. The mean serum concentration of AFP-IgM IC was significantly higher in HCC patients (mean +/- SD: 1378.3 +/- 2935.7 AU/mL) than in cirrhotic patients (129.8 +/- 261.4 AU/mL) and in patients with chronic hepatitis (80.9 +/- 168.9 AU/mL) (p < 0.01). HCC patients had FAFP values above the 20 ng/mL cutoff in 44% of cases (22/50) and AFP-IgM IC values above the 120 AU/mL cutoff in 60% of cases (30/50). The occurrence of the free and IgM-complexed form of circulating AFP did not overlap, and 82% of patients (41/50) were positive for at least one marker. The results indicate that AFP-IgM IC is a complementary serological marker to FAFP and that the combination of these biomarkers may be useful in the diagnosis of liver cancer.     

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.     

Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma

In this study we assessed the usefulness of serum Transforming Growth Factor-beta1 (TGF-beta1) and soluble Fas (sFas) in distinguishing liver cirrhosis (LC) with and without hepatocellular carcinoma (HCC) as compared with alpha-fetoprotein (AFP). Serum TGF-beta1 and sFas levels were measured by ELISA in 51 LC patients, 54 patients with HCC and 30 healthy donors. Considering as a cut-off limit (mean+1SD of controls) 74 pg/ml and 637 pg/ml for TGF-beta1 and sFas, respectively, we computed serum concentrations of TGF-beta1 and sFas as a score (mean+/-SD). The positive frequency of serum TGF-beta1 levels in HCC patients (54%) was greater than in LC patients (26%) and healthy donors (3%). TGF-beta1 levels were higher in HCC (1.6+/-0.5) than in LC (1.1+/-0.2) (P<0.0001) and healthy donors (0.6+/-0.2). Using a cut-off limit of 82 pg/ml (mean+2SD), the positive frequency of TGF-beta1 was 20% in HCC patients. None of the controls and LC patients had TGF-beta1 levels higher than 82 pg/ml. The positive frequency of serum sFas levels was 100% in HCC patients, 98% in LC patients and 3% in healthy controls. Serum sFas levels were higher in HCC (2.5+/-0.7) than in LC (1.9+/-0.5) (P<0. 001) and healthy donors (0.6+/-0.3). No significant change of positive frequency was obtained by setting sFas cut-off at higher levels. sFas values did not correlate with TGF-beta1 levels. No relationship was found between TGF-beta1 amounts and AFP levels. However, in the 23% of HCC patients, with normal AFP values TGF-beta1 levels were higher than the cut off. These findings suggest the potential usefulness for TGF-beta1 assay in AFP-negative HCC.     

多肽抗体检测原发性肝癌血清标志物ELISA方法的建立及应用

血清多肽是癌症诊断信息的重要来源,建立、优化了检测多肽标志物的直接ELISA法,并应用于肝癌血清中的多肽标志物的检测。制备及纯化针对多肽标志物Pep5的单克隆抗体并进行辣根过氧化物酶标记,用其建立检测相应抗原的直接ELISA法。方法线性范围为1.5-20 ng/mL,检测限为1.24 ng/mL;标准品批内及批间CV分别小于3.66%及4.89%,血清样本批内及批间CV分别小于11.69%及18.18%;线性范围内(9、12和15 ng/mL)的回收率分别为98.98%,99.61%和101.58%。应用该方法共检测160例正常血清、104例肝硬化及156例肝癌患者血清,正常组与肝硬化组及肝癌组间差异显著(P<0.001),Pep5诊断肝癌的敏感性和特异性分别为80.8%和96.2%。同时检测94例HCC血清中的AFP和Pep5,AFP检出率为63.8%,Pep5检出率为90.4%,AFP联合Pep5检测时,能将HCC的检出率提高至94.7%。     

人肝癌裸小鼠常位移植实验研究

采用硫贲妥钠（３０ｍｇ／ｋｇ、３０％乙醇配制）麻醉和蘸上立止血（２５０ｋＩＵ／ｍｌ）的明胶海棉止血措施确保了人肝癌裸小鼠常位移植术能安全、可靠地进行。本中心建立的两株人肝癌裸小鼠移植瘤株（ＨＨＣ４、ＨＨＣ１５）已成功地移植于裸小鼠（ＳＰＦ级）肝脏内,移植瘤生长良好、传代稳定和持续分泌ＡＦＰ。荷瘤（ＨＨＣ１５）３～６周裸小鼠血清ＡＦＰ含量与瘤体积的增加呈正相关。常位移植前（７ｄ）裸小鼠皮下注射０．１ｍｌ０．５％ＣＣ１（Ｖ／Ｖ。橄榄油配制）能明显提高ＨＨＣ４常位移植的成功率（Ｘ２检验、Ｐ＜０．０１）;在微量ＣＣｌ４作用下,裸小鼠肝细胞受损伤,发生肝硬化,在此基础上所移植和生长的人肝癌常位移植瘤与大多数人肝癌病变发生的肝脏病理生理学特点相似,本模型的建立更适用于抗肝癌药物的模拟治疗和筛选。     

Using Serum α-Fetoprotein for Prognostic Prediction in Patients with Hepatocellular Carcinoma: What is the Most Optimal Cutoff?

Background and Aims

The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear.

Methods

A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model.

Results

Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively.

Conclusions

This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients.     

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.     

AFP、AFU、β_2-MG、CA199联合检测对原发性肝癌的早期诊断价值

目的：探讨原发性肝癌患者血清甲胎蛋白（AFP）、а-L岩藻糖苷酶（AFU）、β2-微球蛋白（β2-MG）、糖类抗原-199（CA199）的含量及其联合检测对原发性肝癌的早期诊断价值。方法：选择56例原发性肝癌患者、60名肝炎肝硬化患者和60名健康对照作为研究对象,分别应用比值法和化学发光法、生化法检测其血清AFP、AFU、β2-MG、CA199的含量。结果：原发性肝癌患者血清AFP、AFU、β2-MG、CA199含量均显着高于肝炎肝硬化组及健康对照组,差异均有统计学意义（P均〈0.05）;联合检测AFP、AFU、β2-MG、CA199四种肿瘤标志物,其阳性率达（85.7%）明显高于AFP（53.6%）、AFU（55.4%）、β2-MG（48.2%）和CA199（42.9%）单项检测组（P均〈0.05）;且AFP、AFU、β2-MG、CA199四种肿瘤标志物联合检测的敏感性均高于单一检测指标,差异有统计学意义（P〈0.05）,但其特异性显著低于AFU、β2-MG单项检测（P〈0.05）。结论：联合检测血清AFP、AFU、β2-MG、CA199含量可以提高对原发性肝癌的阳性诊断率,对诊断及鉴别诊断原发性肝癌具有重要意义。     

Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma

INTRODUCTION: Serum alpha-fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), although the serum AFP concentration is also increased in patients with chronic liver diseases (CLD). The analysis of AFP glycoforms has been known to be of diagnostic value. We applied the lectin-affinity electrophoresis and antibody-affinity blotting techniques to HCC patients in Vietnam in order to better understand the role of lentil lectin-affinity AFP-L3 in the diagnosis and differential diagnosis of HCC, and its relationship with the biological characteristics of HCC. METHODS: Lens culinaris agglutinin-reactive AFP (AFP-L3) was measured in 65 patients with histologically proven HCC and 25 patients with CLD. All patients had serum AFP levels above 54 ng/mL. AFP-L3 levels were determined by lectin affinity electrophoresis coupled with antibody-affinity blotting. The diagnosis of HCC was confirmed histologically by ultrasound-guided biopsy. RESULTS: The mean value of AFP-L3 in the HCC patients was 49.6 +/- 21.6%, which was significantly higher (p<0.001) than that in the 25 CLD patients (10.7 +/- 4.3%). When the cutoff level for AFP-L3 was set at 15% (mean +/- SD), the sensitivity was 96.9%, the specificity 92.0% and the accuracy 95.5% in the 65 HCC patients. There was no clear correlation between serum AFP level and AFP-L3 percentage (r=0.16). There was no correlation between AFP-L3 and the maximum diameter of HCC nodules (r=0.05). However, the mean AFP-L3 value was higher in moderately or poorly differentiated HCC than in well differentiated tumors (p<0.001). CONCLUSIONS: AFP-L3 is potentially a clinically useful marker for the differentiation of increased AFP levels in hepatocellular carcinoma and chronic liver diseases. The AFP-L3 percentage is closely related to HCC differentiation. We consider the analysis of AFP-L3 a useful adjunct in the diagnosis of HCC.     

The Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection and Cirrhosis

Background

A precise predictive survival model of liver transplantation (LT) with antiviral prophylaxis for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and cirrhosis has not been established. The aim of our study was to identify predictors of outcome after LT in these patients based on tumor staging systems, antitumor therapy pre-LT, and antiviral prophylaxis in patients considered to be unfit by Milan or UCSF criteria.

Methods

From 2002 to 2008, 917 LTs with antiviral prophylaxis were performed on patients with HBV-cirrhosis, and 313 had concurrent HCC.

Results

Stratified univariate and multivariate analyses demonstrated that independent predictors for poor survival were tumor size >7.5 cm (P = 0.001), tumor number >1 (P = 0.005), vascular invasion (P = 0.001), pre-LT serum alpha-fetoprotein (AFP) level ≥1000 ng/ml (P = 0.009), and pre-LT aspartate aminotransferase (AST) level ≥120 IU/L (P = 0.044). Pre-LT therapy for HCC was an independent predictor of better survival (P = 0.028). Based on CLIP and TNM tumor staging systems, HCC patients with HBV-cirrhosis who met the following criteria: solitary tumor ≤7.5 cm, or ≤4 multifocal nodules, the largest lesion ≤5 cm and total tumor diameter ≤10 cm, or more nodules with the largest lesion ≤3 cm, and pre-LT serum AFP level <1000 µg/L and AST level <120 IU/L without vascular invasion and lymph node metastasis who were unfit for UCSF, had survival rates of 89% at 5 years. There was a 47% 5-year survival rate for patients with HCC exceeding the revised criteria.

Conclusions

The current criteria for LT based on tumor size, number and levels of AFP and AST may be modestly expanded while still preserving excellent survival after LT. The expanded criteria combined with antiviral prophylaxis and pre-LT adjuvant therapy for HCC may be a rational strategy to prolong survival after LT for HCC patients with HBV-associated cirrhosis.     

Comparative diagnostic efficacy of serum squamous cell carcinoma antigen in hepatocellular carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) is a common liver malignancy in Nigeria. Hepatitis B and C viruses, alcohol and Aflatoxin B are among the various aetiology. More work needs to be done in the search for markers that will aid early detection of this condition as it is uniformly fatal once advanced. Alphafetoprotein (AFP) remains the most widely used tumour marker of HCC detection in spite of its known shortcomings. The objective of this study was to determine the efficacy of serum squamous cell carcinoma antigen (SCCA) , in comparison to alphafetoprotein in the detection of HCC. METHOD: Sixty patients with HCC and thirty apparently healthy controls attending the Medical Outpatient Department(MOPD) of the University College Hospital Ibadan(UCH) Nigeria were selected for the study. Questionnaire was used to collect clinical data while AFP, SCCA levels,serum HBsAg and anti-HCV were determined using ELISA method- ( Diagnostic Automation Inc. Canada),Abdominal ultrasound scan was also done. Result:Thirty one(51.7%) out of 60 selected cases were positive for HBsAg while six(20%) out of 30 controls were positive for HBsAg(p= 0.004) .Out of the 60 cases selected for this study only 2 (3.3.%) cases were positive for hepatitis C virus, while only 1(3.3%) out of 30 control was positive for hepatitis C virus(p= 0.74). The mean AFP value for cases with HCC was 393.21ng/ml +/-386.97 compared to the control group which was 5.60 +/- 13.03 ng/ml (P value 0.001).The mean SCCA level was 0.64 +/- 0.56ng/ml and 0.71+/-0.65ng/ml for cases and controls respectively (p=0.631) CONCLUSION: Alphafetoprotein remains a good tumour marker for the diagnosis of HCC. Serum squamous cell carcinoma antigen(SCCA) has no discriminatory power and may not be useful as a tumour marker for Nigerians with hepatocellular carcinoma.     

Association of Serum Level of Growth Differentiation Factor 15 with Liver Cirrhosis and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.     

DC-CIK治疗对晚期肝细胞癌患者免疫功能及循环肿瘤细胞的影响

目的:研究DC-CIK细胞治疗对晚期肝细胞癌患者甲胎蛋白、免疫功能及循环肿瘤细胞数的影响。方法:选取2013年至2015年我院收治的26例肝细胞癌并伴有复发或转移的患者,对其治疗前后甲胎蛋白、免疫功能及循环肿瘤细胞数的数据进行分析,比较DC-CIK细胞治疗前后甲胎蛋白、循环肿瘤细胞、免疫功能的变化。根据细胞治疗次数分为1次组及1次组,比较两组免疫功能的变化。结果:DC-CIK细胞治疗前甲胎蛋白为(603.32±155.78)ng/mL细胞回输后为(571.24±147.49)ng/mL差异无统计学意义(P0.05)。DC-CIK细胞治疗前及细胞回输后CTC检测阳性率分别为81.8%、36.4%治疗前及回输后循环肿瘤细胞数量分别为(8.36±10.642)、(1.55±2.464),细胞治疗前后比较差异均有统计学意义(P0.05)。细胞治疗前1天T细胞亚群CD3+、CD3~+CD4~+、CD3~+CD8~+、CD4/CD8分别为(66.05±15.31)%、(41.89±12.33)%、(23.15±8.05)%、(2.10±0.77),回输后分别为(69.69±12.91)%、(44.80±11.11)%、(23.13±7.12)%、(2.29±0.91)治疗前后比较差异无统计学意义(P0.05)。细胞治疗次数1次组和1次组免疫功能变化差异无统计学意义(P0.05)。结论:DC-CIK细胞治疗可减少肝细胞癌伴复发或转移患者循环肿瘤细胞的数量,但对甲胎蛋白和免疫功能无明显影响。     

Alpha-fetoprotein monoclonal assay: preliminary clinical findings in a high risk population

A two-site solid phase immunoradiometric assay was developed for measurement of human alpha-fetoprotein, utilizing two high-affinity monoclonal antibodies directed against distinct and separate epitopes on the proteic structure. The analytical sensitivity of the assay is 0.5 ng/ml. The clinical sensitivity was evaluated by comparison of patients with cirrhosis and patients with hepatocellular carcinoma with cirrhosis. This assay gave good diagnostic discrimination. In a preliminary clinical trial, the specificity of the assay was 92.3%, the clinical sensitivity 88.2%, and predictive values were 78.9% in the clinically positive stage and 96.0% in the negative stage. The diagnostic efficacy of the assay was 91.3%.     

Secreted ERBB3 isoforms are serum markers for early hepatoma in patients with chronic hepatitis and cirrhosis

Most hepatocellular carcinoma (HCC) is generated from chronic hepatitis and cirrhosis. To discover new markers for early HCC in patients with chronic hepatitis and cirrhosis, we initiated our search in the interstitial fluid of tumor (TIF) via differential gel electrophoresis and antibody arrays and identified secreted ERBB3 isoforms (sERBB3). The performance of serum sERBB3 in diagnosis of HCC was analyzed using receiver operating characteristic curves (ROC). The serum sERBB3 level was significantly higher in HCC than in cirrhosis (p < 0.001) and chronic hepatitis (p < 0.001). The accuracy of serum sERBB3 in detection of HCC was further validated in two independent sets of patients. In discrimination of early HCC from chronic hepatitis or cirrhosis, serum sERBB3 had a better performance than alpha-fetoprotein (AFP) (areas under ROC [AUC]: sERBB3 vs AFP = 93.1 vs 81.0% from chronic hepatitis and 70.9 vs 62.7% from cirrhosis). Combination of sERBB3 and AFP further improved the accuracy in detection of early HCC from chronic hepatitis (AUC = 97.1%) or cirrhosis (AUC = 77.5%). Higher serum sERBB3 levels were associated with portal-vein invasion and extrahepatic metastasis of HCC (p = 0.017). Therefore, sERBB3 are serum markers for early HCC in patients with chronic hepatitis and cirrhosis.     

Are 90K/MAC-2BP serum levels correlated with poor prognosis in HCC patients? Preliminary results

In this study we assessed the prognostic significance of 90K/MAC-2BP serum levels in a group of 40 hepatocellular carcinoma patients. This glycoprotein is a new, interesting serum marker that reflects the immune reaction of the host against certain viral infections and tumors such as breast, ovarian and pancreatic cancer. Hepatocellular carcinoma (HCC) is one of the most widespread tumors in the world. AFP is currently the most useful marker for HCC, in spite of its poor diagnostic sensitivity. In this study 40 cirrhotic HCC patients were enrolled. The prevalence of viral hepatic infections in this group was 73% for HCV, 8% for HBV, and 8% for both viruses. Thirteen percent of the patients showed non-virus-related liver damage. 90K serum levels were assayed by an ELISA kit and AFP levels by a chemiluminescent enzyme immunometric system. The overall survival curves were estimated by the Kaplan-Meier method, taking into account age, sex, 90K and AFP serum levels. Statistical analysis showed a highly significant influence on overall survival of age below 70 years and 90K serum levels below the cutoff of 14 ng/mL. Serum AFP (< or = 20 ng/mL) had positive prognostic value only when it was associated with 90K levels (p < 0.02, log-rank).     

Serum levels of carcinoembryonic antigen, gastrointestinal cancer-associated antigen and alphafetoprotein in staging and management of patients with advanced carcinoma of the stomach

Serum levels of carcinoembryonic antigen (CEA), gastrointestinal cancer-associated antigen (GICA or CA 19-9), and alphafetoprotein (AFP) were concurrently determined in patients with carcinoma of the stomach: in 84 preoperatively, and in 67 serially postoperatively. Before surgery, serum CEA gave information about the tumor load analogous to serum GICA in 69% of the patients: true-positive in 25% and false-negative in 43%; less information in 18% and more in 14%. The sensitivity of the test tended to be better in the more advanced stages, and was higher for CEA with GICA than for CEA alone or GICA alone. During follow-up, serum CEA gave information about the presence or absence of active disease analogous to serum GICA in 78% of the patients: true-positive in 30%, true-negative in 36% and false-negative in 12%; less information in 9% and more in 13%. Neither test gave any false-positive indications. Sensitivity of the test rose from 67% for CEA alone and 60% for GICA alone to 81% for CEA with GICA. Serum AFP was elevated only preoperatively in 2% of patients. We conclude that joint application of CEA and GICA tests gave only slightly better preoperative sensitivity than CEA alone or GICA alone but proved fairly sensitive for postoperative follow-up of the patients. AFP was of little value for either purpose.     

肝癌患者经系统治疗后甲胎蛋白变化对预后的影响

目的:探讨肝癌患者经系统治疗后甲胎蛋白(AFP)变化对患者预后的影响。方法:对53例肝癌患者于入院后和系统治疗后分别于不同时间点测定血清AFP值后,将入院时AFP值作为基线,以变化50%作为标准分组,并进行无疾病进展生存时间(PFS)和总生存时间(OS)分析。结果:9例患者血清AFP值下降超过50%(A组),28例患者AFP值升高超过50%(B组),而AFP值变化小于50%(C组)的为16例。和C组相比,A组患者PFS明显延长(P<0.05),B组PFS明显缩短(P<0.05)。B组OS短于C组(P<0.01),而A组和C组间OS无明显差别(P>0.05)。结论:肝癌系统治疗前后的AFP值变化可作为临床上预后判断的标志之一。