To comparatively investigate ultrastructural characteristics and expressions of AFP (alpha-fetoprotein) and Tn (Thomsen-Friedenreich-related antigen) protein in AFP negative (AFP-) and AFP positive (AFP+) primary hepatocellular carcinoma. Fourty-three cases of AFP- and AFP+ hepatocellular carcinoma (HCC) tissues and five cases of normal liver tissues were divided into three groups: control group (normal liver tissue, n=5); AFP+ HCC group (the serum AFP level was higher than 10 ng/ml, n = 22); AFP- HCC group (the serum AFP level was lower than 10 ng/ml, n=21). The ultrastructural morphology was studied by transmission electron microscopy, the expressions of AFP and Tn protein were detected by immunohistochemistry and cell image analysis. 1. The immunohistochemical study showed that (1) the expression intensity and positive rate of Tn protein in AFP- HCC group were markedly higher than that in AFP+ HCC group (P<0.01); (2) The expression intensity of AFP in AFP- HCC group was lower than that in AFP+ HCC group (P<0.01). 2. The transmission electron microscopy demonstrated that some AFP- HCC cells linked closely with each other, others dispersed loosely just as cultured cells, the remarkable morphologic features in AFP- HCC cells were simple organelles, but they were abundant in the free polyribosomes. In AFP+ HCC group, all the HCC cells linked closely together and were rich organelles in their cytoplasm, especially the rough endoplasmic reticula. In addition, mitochondria and Golgi complex were obviously observed. (1) The AFP and Tn protein had discrepancy distribution in AFP- and AFP+ HCC tissues, Tn protein may be one of the early diagnostic indicators in AFP- HCC; (2) The synthetic locations of the AFP and Tn protein were different in hepatocarcinoma cells by ultrastructural observation.
Antigens, Tumor-Associated, Carbohydrate ; biosynthesis ; genetics ; Biomarkers, Tumor ; Carcinoma, Hepatocellular ; metabolism ; ultrastructure ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; metabolism ; ultrastructure ; Male ; Tumor Cells, Cultured ; alpha-Fetoproteins ; biosynthesis ; genetics

PURPOSE: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCel(TM) DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. MATERIALS AND METHODS: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA Centaur(TM) and Vitros(TM) ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. RESULTS: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCel(TM) DxI 800 were highly correlated with those from other analyzers. CONCLUSION: Our results demonstrate that UniCel(TM) DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken, and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.
CA-125 Antigen/blood ; CA-19-9 Antigen/blood ; Carcinoembryonic Antigen/blood ; Humans ; Immunoassay/*instrumentation/*methods ; Tumor Markers, Biological/*blood ; alpha-Fetoproteins/metabolism

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; Female ; Humans ; Male ; Middle Aged ; Mucin-1 ; blood ; Neoplasms ; blood ; complications ; diagnosis ; Prostate-Specific Antigen ; blood ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; blood ; Venous Thrombosis ; blood ; complications ; Young Adult ; alpha-Fetoproteins ; metabolism

BACKGROUNDIt is often challenging to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE); thoracoscopy is among the techniques with the highest diagnostic ability in this regard. However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition. The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) associated antigen in patients with TPE and MPE.

METHODSUsing electrochemiluminescence, we measured the concentration of tumor markers (TMs) in the pleural effusion and serum of patients with TPE (n = 35) and MPE (n = 95). We used receiver operating characteristic (ROC) curve analysis to evaluate the TMs and differentiate between TPE and MPE.

RESULTSThe cut-off values for each TM in serum were: CA125, 151.55 U/ml; CA199, 9.88 U/ml; CEA, 3.50 ng/ml; NSE, 13.27 ng/ml; and SCC, 0.85 ng/ml. Those in pleural fluid were: CA125, 644.30 U/ml; CA199, 12.08 U/ml; CEA, 3.35 ng/ml; NSE, 9.71 ng/ml; and SCC, 1.35 ng/ml. The cut-off values for the ratio of pleural fluid concentration to serum concentration (P/S ratio) of each TM were: CA125, 5.93; CA199, 0.80; CEA, 1.47; NSE, 0.76; and SCC, 0.90. The P/S ratio showed the highest specificity in the case of CEA (97.14%). ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid (0.95) was significantly different from that in serum (0.85; P < 0.001).

CONCLUSIONSTMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid. The combined detection of TMs can improve diagnostic sensitivity.

Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; Carcinoembryonic Antigen ; blood ; Electrochemical Techniques ; Female ; Humans ; Luminescent Measurements ; Male ; Middle Aged ; Pleural Effusion ; blood ; Pleural Effusion, Malignant ; blood ; Young Adult

BACKGROUND: Specimens for the external quality assessment (EQA) need to be highly stable during the EQA process. Therefore, we evaluated the stability of pooled sera (PS) for tumor markers including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), and carbohydrate antigen 19-9 (CA 19-9). METHODS: PS with 2 different levels (high and low) of each of the 4 tumor markers were collected and stored at -20degrees C, 4degrees C, and room temperature (RT). The concentration of each tumor marker was then measured after storage under these different conditions at baseline and on days 1, 3, 7, 14, 30, 90, and 181. Internal quality control (QC) results during the evaluation period were also analyzed. RESULTS: Irrespective of storage conditions, coefficients of variation (CVs) of AFP and CA 125 levels in the PS during the evaluation period ranged from 3.3% to 7.5% in EQA assays and were similar to the CVs of QC assays. However, the levels of CEA detected in PS stored at -20degrees C, and 4degrees C, showed higher variability, with CVs ranging from 4.0% to 10.4%, and samples stored at RT showed especially high CVs, i.e., >8.3%. Samples for CA 19-9 testing stored at RT also showed lower stability than the QC samples as well as samples stored at -20degrees C, after 3 days. CONCLUSIONS: CEA and CA 19-9 levels in PS showed higher variability than AFP and CA 125, especially when stored at RT. These results indicate that all EQA specimens for tumor marker assays need to be tested as soon as possible and not stored at RT for longer than 3 days during the EQA process.
alpha-Fetoproteins ; Carcinoembryonic Antigen ; Quality Control ; Biomarkers, Tumor

OBJECTIVETo identify the optimal combination of serum tumor markers with bioinformatics in diagnosis of colorectal cancer.

METHODSThe serum levels of CEA, AFP, NSE, CA199, CA242, CA724, CA211 and TPA were detected in 128 patients with colorectal carcinoma and 113 health subjects. The serum tumor markers were evaluated with the area under curves. The optimal combination of serum tumor markers was selected and the diagnostic model with artificial neural network was established.

RESULTSCEA, CA199, CA242, CA211, CA724 were selected for the optimal combination and the artificial neural network was built. The model was evaluated by a 5-cross validation approach. The model had a specificity of 95%, sensitivity of 83% and positive predictive value of 95% in diagnosis of colorectal carcinoma.

CONCLUSIONThe combination of optimal serum tumor markers has a high sensitivity and specificity in diagnosis of colorectal carcinoma.

Adult ; Aged ; Aged, 80 and over ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Neural Networks (Computer) ; Sensitivity and Specificity

OBJECTIVETo investigate the diagnostic value and clinical significance of serum tumor markers CEA, CA19-9 and CA242 in patients with colorectal cancer.

METHODSThe serum levels of CEA, CA19-9 and CA242 were determined by ELISA before surgery in 134 patients with colorectal cancer and in 200 healthy people as a control.

RESULTSThe CEA, CA19-9 and CA242 levels in patients were significantly higher than those in controls (P < 0.01, respectively). The sensitivity of CEA and CA242 for colorectal cancer diagnosis was higher than that of CA19-9, and the combined sensitivity of CEA + CA242 and CEA + CA242 + CA19-9 were higher than that of single item or the other two combinations (CEA + CA19-9 and CA19-9 + CA242). In Dukes stages A, B, C and D, serum levels and sensitivity of the three tumor markers were significantly and successively increased. In the cases with lymph node metastasis, levels of the three tumor markers were significantly increased. The markers levels were also significantly and successively increased along with the extent of cancer infiltration.

CONCLUSIONThe results indicate that the combined use of CEA and CA242 or the three markers is an useful adjuvant diagnostic measure for colorectal cancer, and is helpful in the evaluation of lymph node metastasis, degree of invasion and Dukes staging in cancer treatment.

Adult ; Aged ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; diagnosis ; pathology ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Sensitivity and Specificity

OBJECTIVETo investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer.

METHODSOne hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis.

RESULTSOn initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor (P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4 (P=0.006, P=0.002).

CONCLUSIONSTumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.

Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; blood ; diagnosis ; pathology

Mucinous tumors account for 10-15% of all epithelial of ovarian tumors, and 40% of them are borderline. Not many factors are known about progression into mucinous carcinoma of borderline ovarian tumors. The incidence of progression into invasive carcinoma is reported about 2.4% for borderline serous tumous, and 1.6% for borderline mucinous ovarian tumors. Mucinous tumors often exhibit a morphologic continuum of beningn, borderline, and invasive, so a pathologist should pay attention when examine the pathologic specimen not to miss carcinoma. This is the case of 54 female patients who developed invasive mucinous ovarian carcinoma 6 months after surgical treatment of borderline mucinous ovarian tumour.
Adenocarcinoma, Mucinous ; Cystadenocarcinoma, Mucinous* ; Female ; Humans ; Incidence ; Mucins* ; Tumor Markers, Biological* ; Biomarkers, Tumor

BACKGROUND: The sensitivity and specificity of tumor markers for detecting cancer could be significantly changed by the reference intervals of tumor markers. We established reference intervals of tumor markers in Korean adults and evaluated its importance, since the reference intervals recommended by the manufacturers were determined in the Caucasian population and have sometimes been adopted without verification. METHODS: We established the reference intervals of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)125, carbohydrate antigen (CA)19-9, total prostate specific antigen (TPSA), cytokeratin fragment (Cyfra)21-1, and neuron specific enolase (NSE) according to the CLSI guideline in a maximum number of 1,364 healthy adults aged 20-60 yrs who visited a health promotion center from January to February 2007. RESULTS: Reference intervals of all tumor markers except for AFP were not in agreement with those recommended by the manufacturers. Reference intervals of CEA, TPSA, CA19-9, CA125, and Cyfra21-1 were age dependent. The mean reference values of NSE, CA125, and CEA were statistically different according to gender (11.72 vs 10.78 ng/mL), menopause status (18.89 vs 12.62 U/mL), and smoking status (2.60 vs 2.12 vs 1.80 ng/mL for smokers, past smokers, and non-smokers, respectively),respectively. CONCLUSIONS: With the verification and establishment of reference intervals of tumor markers in a Korean local population, we found the reference intervals significantly different by either age, gender, smoking or menopause status.
Adult ; Age Factors ; Carcinoembryonic Antigen/analysis ; Female ; Humans ; Korea ; Male ; Menopause ; Middle Aged ; Phosphopyruvate Hydratase/analysis ; Prostate-Specific Antigen/analysis ; Questionnaires ; Reagent Kits, Diagnostic ; Reference Values ; Sex Factors ; Smoking ; Tumor Markers, Biological/*standards ; alpha-Fetoproteins/analysis