Plasma levels of cellular fibronectin in patients with localized and metastatic renal cell carcinoma.

Clinical markers for renal cell carcinoma (RCC) are lacking. Fibronectin is a glycoprotein that plays an important role in cellular attachment and cell spread. The aim of this study was to test the clinical suitability of cellular fibronectin (cFN) in plasma as a tumor marker for RCC and to determine a possible relationship between cFN plasma levels and stage of disease. Therefore, cFN was determined in the plasma of patients with localized (n = 40) and metastatic (n = 20) RCC using a time-resolved fluorescence immunoassay. Fifty patients with different non-malignant urological disorders were recruited as a control group. In the control group, mean cFN plasma levels amounted to 553 ng/ml. In patients with localized RCC, plasma concentrations of cFN were increased (1,295 ng/ml; p < 0.01). Patients with metastatic disease had the highest concentrations (3,842 ng/ml). Statistical analysis demonstrated a significant difference between controls, and patients with localized and metastatic RCC (p < 0.01), with a sensitivity of 80%, a specificity of 78% and a positive predictive value of 81% using a cutoff value of 540 ng/ml (receiver-operating characteristic curve analysis). These data suggest that cFN is not a realistic marker for the detection of RCC. However, elevated plasma levels in more advanced disease and an acceptable predictive value could indicate that cFN is useful as a follow-up tool in the management of RCC patients.

Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan.

BACKGROUND/AIMS: Modifications of the Child-Pugh classification of liver cirrhosis by incorporation of hyaluronan were tested to improve the prognostic power for long term evaluation of liver cirrhosis in 126 patients observed over a period of 10 years. METHODS: Serum concentrations of HA were determined at study entry. Statistical analysis included Kaplan-Meier life tables and stepwise multivariant Cox-regression analysis for each parameter of Child-Pugh classification and hyaluronan. Prognostic models were developed by exchanging prothrombin time, albumin and encephalopathy by HA in different combinations. RESULTS: Based on a good single correlation between hyaluronan (0.62) and clinical course (P<0.01) we conclude that models with hyaluronan instead of albumin or encephalopathy and with or without shifted threshold values of bilirubin and albumin are superior for the prediction of the long term prognosis. In Cox-regression analysis, apart from hyaluronan and bilirubin, no other parameters contributed to an improvement. CONCLUSIONS: We conclude that a modification of the Child-Pugh classification of liver cirrhosis by inclusion of HA significantly improves the predictive power of CP, especially in alcoholic etiology. A prospective validation of the newly defined scores needs to be done in the future.

Cellular fibronectin in patients with transitional cell carcinoma of the bladder.

Various tumor markers for transitional cell carcinoma (TCC) of the bladder have been described, but none of them are used in clinical routine. Fibronectin, a glycoprotein, seems to play a very important role in both the progression and invasion of cancer. The aim of this study was to evaluate cellular fibronectin (cFN) in the urine and blood of patients with TCC of the bladder and to determine its possible role as a tumor marker and prognostic factor. Morning urine samples and blood were collected from 20 patients (8 women, 12 men, mean age 69.9 years) before they underwent transurethral resection of bladder tumors (TURB). Twenty patients (10 women, 10 men, mean age 63.4 years) with nonmalignant urological disorders were recruited as the control group. Determination of cFN in plasma and urine was performed by using a newly developed time-resolved fluorescence immunoassay (TRFIA). Patients with nonmalignant diseases had mean cFN plasma levels of 404 ng/ml (range 181-746 ng/ml). Patients with TCC of the bladder showed significantly higher cFN plasma levels of 686 ng/ml (range 274-1999 ng/ml, p<0.05). Subdivided according to the TNM system, muscle-invasive bladder tumors (n=5) demonstrated higher cFN plasma levels (mean 944 ng/ml) than superficial bladder tumors (n=15, mean 463 ng/ml). There were no differences of plasma cFN concentrations concerning tumor grade and also no differences in urine levels between the different groups. We found a significant difference (p<0.04) of cFN plasma levels between patients with TCC of the bladder and the control group. The difference in cFN plasma levels between pTa/pT1 and >or=pT2 tumors indicates a clinically useful potential of this tumor marker for preoperative staging and postoperative follow-up. Our data underline the important but still unclear role of cFN as a tumor marker in TCC, and this will be the focus of future studies.

Further arguments against including trisialo-Fe2-transferrin in carbohydrate-deficient transferrin (CDT): a study on male alcoholics and hazardous drinkers.

BACKGROUND: We attempted to determine whether including trisialo-Fe2-transferrin in carbohydrate-deficient transferrin (CDT) affects the diagnostic accuracy of CDT as a marker of chronic excessive alcohol intake. MATERIAL/METHODS: The criterion standard tests for the diagnosis of alcoholism and alcohol intake were the Composite International Diagnostic Interview (CIDI) and the Timeline-Followback (TLFB). The study groups (alcohol intake in each of the last 4 weeks before blood sampling) were comprised of 56 controls (< or = 280 g/week, no alcoholism), 54 hazardous drinkers (>280 g/week, no alcoholism), 63 alcoholics (>280 g/week, alcoholism diagnosis). CDT analysis was performed with %CDTri-TIA, which includes about 50% of trisialo-Fe2-transferrin in CDT, and ChronAlcoI.D, which excludes this transferrin isoform from CDT. RESULTS: Depending on the cut-offs for the CDT/transferrin ratio (upper or lower limit of the test-specific borderlines) and on the patient group, the diagnostic sensitivity was 28.1%-72.3% for %CDTri-TIA, as opposed to 50.0%-82.5% for ChronAlcoI.D. The diagnostic accuracy was 62.8%-78.5% for %CDTri-TIA and 71.8%-86.6% for ChronAlcoI.D. The latter test consistently showed higher diagnostic sensitivity and accuracy than %CDTri-TIA. The diagnostic specificity was 85.7%-98.2% for %CDTri-TIA and 91.1%-92.2% for ChronAlcoI.D. The areas under the ROC curve were 0.810%-0.885 for %CDTri-TIA and 0.867%-0.896 for ChronAlcoI.D. CONCLUSIONS: The present study and data from the literature indicate that including parts of trisialo-Fe2-transferrin by the %CDTri-TIA test significantly reduces the diagnostic sensitivity and thus accuracy of CDT as a marker of chronic excessive alcohol use.

TGF-beta1 in patients with renal cell carcinoma.

Up to now, clinical tumor-markers for renal cell carcinoma (RCC) have been lacking. Increased plasma levels of transforming growth factor-beta1 (TGF-beta1) were described as a tumor-marker and prognostic factor in RCC. The aim of this study was to test the clinical suitability of plasma TGF-beta1 as a tumor-marker for RCC. The concentrations of active and latent TGF-beta1 were determined in plasma of patients with localized (n = 39) and metastasised (n = 17) RCC. A newly developed, highly sensitive ELISA, which is specific for the isoform beta1, was used. Active TGF was directly measured in the EDTA plasma. To determine the amount of latent TGF-beta1, which is bound predominantly at beta2-macroglobulin, an optimized activation procedure was applied. Patients with localized RCC showed median concentrations of 16,700 ng/l (6,200-54,800 ng/l) for latent TGF-beta1. A total of 94 patients with various nonmalignant urological diseases were recruited as a control group. In comparison, this group had median concentrations of 19,900 ng/l (2,640-52,300 ng/l) for latent TGF-beta1. There was no significant difference (nonparametric Kruskal-Wallis ANOVA) between these groups. Patients with metastatic RCC showed median concentrations of 34,500 ng/l (6,800-48,960 ng/l) for latent TGF-beta1. In comparison to the localized RCC group, a statistically significant difference was found. Plasma levels after operative therapy (days 1, 5 and 10) and during follow-up without evidence of disease (2-6 months) showed no significant differences. Contrary to other study groups, our results suggest that TGF-beta1 is not a suitable tumor-marker for the diagnosis of localized RCC. In the face of higher TGF-beta1 plasma levels in metastatic disease, TGF-beta1 may be useful in the early detection of RCC recurrence or to control the success of immunochemotherapy.

A prolonged time interval between blood sample collection and centrifugation causes an increase in serum carbohydrate-deficient transferrin.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is used for the laboratory diagnosis of chronic alcohol abuse. Non-optimal preanalysis can cause an increase in CDT and false positive results. The aim of our study was to determine whether CDT results change over time between collection of the blood sample and centrifugation, and whether shipment of whole blood samples is a potential source of false positive CDT reports. MATERIAL/METHODS: 152 blood samples were drawn from 38 persons (4 tubes per person, one venipuncture) and randomly assigned to 4 groups with different time intervals between blood sample collection and centrifugation (1h, 24h, 48h, 144h). CDT analysis was done using the ChronAlcoI.D. assay. The statistical analysis was based on box-plots, ANOVA and Kruskal-Wallis ANOVA. RESULTS: The means and medians of CDT increased with the time of whole blood storage. ANOVA analysis of between-group differences was significant for mean CDT concentrations between 1 and 144 hours of whole blood storage. There was no correlation between CDT and free hemoglobin as a measure of hemolysis. An interference of hemolysis with CDT measurement can be excluded as the main cause of increased CDT results with whole blood storage time. Whether an in vitro degradation of the transferrin N-glycan chains causes the CDT increase should be evaluated by isoelectric focusing of the transferrin isoforms in a further study. CONCLUSIONS: Storage or shipment of whole blood samples can shift initially normal CDT values to borderline and borderline to pathological CDT results.