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ABSTRACT: Malignant pleural mesothelioma (MPM) is a lethal tumor related to asbestos exposure. At present, the only instruments for screening and diagnosis are based on radiological tests, posing evident economic and radio-protectionist problems. Some authors are evaluating biological indicators, such as plasma osteopontin (pOPN) and serum soluble mesothelin-related peptides (SMRP). This study aimed to evaluate whether a combination of these two markers could increase sensitivity and specificity in diagnosis of epithelioid MPM.
We enrolled 93 healthy subjects, 111 individuals with benign respiratory disease (BRD), and 31 patients with MPM, histologically and/or cytologically confirmed. SMRP and pOPN levels were determined using commercially available enzyme-linked immunosorbent assay kits. Though a logistic regression analysis, SMRP and pOPN were combined and translated into a new index, called "combined risk index."
Differences in both SMRP and pOPN mean values between epithelial MPM patients and healthy subjects or BRD patients were statistically significant (p < 0.0001), whereas there was no difference in SMRP and pOPN mean values between healthy subjects and BRD patients. The performance in MPM diagnosis resulted improved by the combination of the two markers. The results of our study should be confirmed by a larger scale and, possibly, a multicenter study, which could better take into consideration the influence of some possible confounding factors such as glomerular filtration rate and other blood parameters.
We combined SMRP and pOPN dosages to increase diagnostic accuracy. This study showed for the first time that combined SMRP and pOPN measurements can increase both sensitivity and specificity in terms of combined risk index.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2011; 6(9):1587-93. · 4.55 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) is a highly aggressive and invasive tumor, whose incidence is expected to peak, in many countries, at the end of the present decade, 20-40 years after the peak of asbestos use (asbestos being the most important etiological factor). MPM has a poor prognosis, in part, owing to a difficult and often late diagnosis hindered by a lack of available tests able to diagnose or predict this cancer in its early stages. Recently, there has been increased interest in noninvasive, economic and well-accepted diagnostic tests for screening of asbestos-exposed subjects, as well as for monitoring response of MPM patients to treatment. Several markers have been studied in biofluids, such as serum, plasma and pleural effusions, especially using ELISA, and some of them are still under investigation. However, only mesothelin and ostepontin have proven levels of sensitivity and specificity that are worth testing in the clinical setting.
Biomarkers in Medicine 04/2011; 5(2):261-73. · 0.86 Impact Factor
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Alfonso Cristaudo, Rudy Foddis,
Alessandra Bonotti,
Silvia Simonini,
Agnese Vivaldi,
Giovanni Guglielmi,
Nicolino Ambrosino,
Pier Aldo Canessa,
Antonio Chella,
Marco Lucchi,
Alfredo Mussi,
Luciano Mutti
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ABSTRACT: A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos.
The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients.
We found that both serum and plasma OPN levels were influenced by storage at -80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN.
These data suggest that plasma OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.
The International journal of biological markers 09/2010; 25(3):164-70. · 1.48 Impact Factor
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ABSTRACT: Serum mesothelin, also known as soluble mesothelin-related protein (SMRP), reportedly shows increased levels in epithelial-type malignant pleural mesothelioma, but sometimes also arrives at high values in healthy asbestos-exposed subjects.
This study aimed to investigate whether single nucleotide polymorphisms in the 3'untranslated region (3'UTR) of the mesothelin-encoded gene (MSLN) are associated with the SMRP levels measured in serum.
The 3'UTR of the mesothelin gene was genotyped in 59 healthy asbestos-exposed subjects, selected on the basis of their SMRP levels. Direct sequencing did not show any new polymorphism, but enabled us to genotype two known SNPs (rs1057147, rs57272256). Differences in the mean values of SMRP in wild-type and variant heterozygote groups were calculated.
High levels of SMRP in healthy asbestos-exposed subjects were significantly associated with polymorphism rs1057147 (G<A). Regarding rs57272256, there was no statistically significant difference between wild-type and heterozygote groups. Our study suggests that rs1057147 polymorphism can affect mesothelin expression. Although these data need to be confirmed with a larger number of cases, this study warrants further research in order to better understand the relationship between mesothelin polymorphisms and SMRP.
Occupational and environmental medicine 10/2009; 67(4):233-6. · 3.64 Impact Factor
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Alfonso Cristaudo, Rudy Foddis,
Agnese Vivaldi,
Giovanni Guglielmi,
Nicola Dipalma,
Rosangela Filiberti,
Monica Neri,
Marcello Ceppi,
Michela Paganuzzi,
Gian Paolo Ivaldi,
Manlio Mencoboni,
Pier Aldo Canessa,
Nicolino Ambrosino,
Antonio Chella,
Luciano Mutti,
Riccardo Puntoni
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ABSTRACT: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled.
SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker.
SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM.
Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.
Clinical Cancer Research 09/2007; 13(17):5076-81. · 7.74 Impact Factor
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Alfonso Cristaudo, Rudy Foddis,
Agnese Vivaldi,
Rodolfo Buselli,
Vittorio Gattini,
Giovanni Guglielmi,
Francesca Cosentino,
Franco Ottenga,
Eugenio Ciancia,
Roberta Libener,
Rosangela Filiberti,
Monica Neri,
Piergiacomo Betta,
Mauro Tognon,
Luciano Mutti,
Riccardo Puntoni
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ABSTRACT: We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb- and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40- was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.
Cancer Research 05/2005; 65(8):3049-52. · 7.86 Impact Factor
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ABSTRACT: Increased concentrations of soluble mesothelin-related peptides (SMRP) have been found in sera of patients with malignant pleural mesothelioma (MPM) even if a relatively high rate of false positives has hampered their clinical use as a tumor marker. Individual SMRP levels could be affected by polymorphic elements. The aim of this study was to investigate the association between single nucleotide polymorphisms within the promoter-5'UTR regions and SMRP levels in healthy asbestos-exposed individuals and patients suffering from MPM.?
The promoter-5'UTR regions of the mesothelin gene were genotyped in 59 healthy asbestos-exposed subjects and 27 MPM patients. SMRP levels were measured using a commercially available ELISA kit.?
Two novel polymorphisms, an A>C variant (called New1) and a C>T variant (called New2), were identified. In healthy subjects, high SMRP levels were associated with the C-variant of New1, with an average 1.62-fold increase compared with AA homozygotes (p<0.0001). Most of the C-allele carriers had SMRP levels above the threshold of 1.00 nM. We set two different SMRP cutoffs on the basis of the combined New1+New2 genotypes.?
New1-New2 genotypes could be employed as markers for setting individualized and appropriate thresholds of "normality" when SMRP is used in surveillance programs of asbestos-exposed people.
The International journal of biological markers 26(2):117-23. · 1.48 Impact Factor
