Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos.

The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers.

Simultaneous determination of 3-nitrotyrosine, tyrosine, hydroxyproline and proline in exhaled breath condensate by hydrophilic interaction liquid chromatography/electrospray ionization tandem mass spectrometry.

The analysis of biomarkers from exhaled breath condensate (EBC) is a non-invasive but challenging method for the detection of pulmonary diseases. The amino acids L-proline (Pro) and l-tyrosine (Tyr) are precursors for two important metabolites, trans-L-4-hydroxyproline (trans-L-4-hydroxypyrrolidin-2-carboxylic acid, t-Hyp) and nitrotyrosine (NT). Whereas t-Hyp is supposed to be a biomarker for lung fibrosis, NT is a promising biomarker for inflammation in airway diseases. Analysis of EBC requires extremely sensitive methods, because the epithelial lining fluid of the lung and upper airway is highly diluted in EBC. The high intra- and interindividual variation of this dilution implicates additional problems for sample collection and the interpretation of EBC results. Hence, our aim was to work out a method that would compensate for these possible dilution effects. We have developed a new, reliable and very sensitive method for the simultaneous determination of Pro, t-Hyp, Tyr and NT from EBC. Except for t-Hyp, we used labelled internal standards (IS) L-proline (13)C(5), (15)N (Pro (13)C(5)), L-tyrosine-(13)C(9) (Tyr (13)C(9)), (13)C(9)-3-nitrotyrosine (NT(13)C(9)), IS for t-Hyp was cis-4-hydroxy-L-proline, which were added to the samples before they were lyophilised for concentration. For the separation of the analytes we used hydrophilic interaction liquid chromatography (HILIC), coupled to tandem-mass-spectrometry (MS/MS). The limit of detection (LOD) was 0.5 microg/l for Pro and Tyr and 5 ng/l for t-Hyp and NT. The relative standard deviation (RSD) of the precision from day to day was between 2.6 and 8.0% at spiked concentrations between 4 and 25 microg/l for Pro and between 4.2 and 7.3% for Tyr. The RSD of the precision from day to day was between 7.5 and 13.2% at spiked concentrations between 40 and 250 ng/l for t-Hyp and between 3.5 and 8.2% for NT. The method was established using 27 healthy subjects with a median age of 46 years. Concentrations ranged from 2.8 to 51.9 microg/l for Pro, from <5 to 516.5 ng/l for t-Hyp, from 2.4 to 99.1 for Tyr and for NT concentration ranged between <5 and 1686.5 ng/l.

Simultaneous determination of the advanced glycation end product N (epsilon)-carboxymethyllysine and its precursor, lysine, in exhaled breath condensate using isotope-dilution-hydrophilic-interaction liquid chromatography coupled to tandem mass spectrometry.

Analysis of biomarkers in exhaled breath condensate (EBC) is a non-invasive method for investigating the effects of different diseases or exposures, on the lungs and airways. N(epsilon)-carboxymethyllysine (CML) is an important biomarker of advanced glycation end products (AGEs). A method has been developed for simultaneous determination of CML and its precursor, the amino acid lysine, in exhaled breath condensate (EBC). After addition of labelled internal standards (d-4-CML; d-4-lysine), the EBC was concentrated by freeze-drying. Separation and detection of the analytes were performed by hydrophilic-ion liquid chromatography coupled with tandem mass-spectrometric detection (HILIC-MS-MS). The limits of quantification were 10 pg mL(-1) EBC and 0.5 ng mL(-1) EBC for CML and lysine, respectively. The relative standard deviation of the within-series precision was between 2.8 and 7.8% at spiked concentrations between 40 and 200 pg mL(-1) for CML and between 6 and 20 ng mL(-1) for lysine. Accuracy for the analytes ranged between 89.5 and 133%. The method was used for the analysis of EBC samples from ten healthy persons from the general population and ten persons receiving dialysis. CML and lysine were detected in all EBC samples with median values of 19 pg mL(-1) CML and 11.9 ng mL(-1) lysine in EBC of healthy persons and 25 pg mL(-1) CML and 9.5 ng mL(-1) lysine in EBC of dialysis patients.

[Occupation related thoracic tumors]. / Berufsbedingte Thoraxtumoren.

It is estimated that about 4% of cancer mortality is attributed to occupational risk factors. Due to long latency periods it is often difficult to establish causal relationships. Thoracal cancer accounts for about 88% of all compensated occupational cancers in Germany. Most important exposures and diseases are asbestos-related lung cancer, asbestos-related malignant mesothelioma and radiation induced lung cancer (by Radon and its decay products). Lung cancer caused by nickel compounds, hexavalent chromium, arsenic and its compounds, coke oven gases and polycyclic aromatic hydrocarbons are rare. Silica-dust induced lung cancer can be compensated as occupational disease if a silicosis is present. In Germany every physician is obliged to notify a suspected occupational cancer as well as other occupational diseases.