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BACKGOUND: Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-γ) in the pleural exudate and their relationship with overall survival (OS) in MPM. METHODS: Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan-Meier curves) and multivariate (Cox regression) analyses. RESULTS: Regarding outcome, tumor histology, therapies undergone and IFN-γ were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-γ halved death probability (HR of high vs low IFN-γ concentration = 0.491, 95%CI 0.3-0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-γ level was an independent factor predictive of OS (HR of high vs low IFN-γ concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-γ levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival. CONCLUSIONS: High level of IFN-γ in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.
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Interferón gamma/metabolismo , Mesotelioma Maligno/patología , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurales/patología , Adulto , Anciano , Citocinas/análisis , Femenino , Humanos , Masculino , Mesotelioma Maligno/inmunología , Mesotelioma Maligno/mortalidad , Persona de Mediana Edad , Derrame Pleural Maligno/inmunología , Neoplasias Pleurales/inmunología , Neoplasias Pleurales/mortalidad , Pronóstico , Estudios RetrospectivosRESUMEN
CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18-0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients.
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Antígeno CTLA-4/metabolismo , Mesotelioma/genética , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Mesotelioma/mortalidad , Mesotelioma/patología , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaRESUMEN
Soluble mesothelin-related peptide (SMRP) is regarded as an FDA approved biomarker for the diagnosis and monitoring of pleural malignant mesothelioma (MPM). We detected the SMRP levels in pleural effusions (PE) by means of an ELISA and analyzed their diagnostic relevance to differentiate MPM from benign pathology and from non-MPM pleural metastasis. Comparison with cytology in MPM-PE was also performed. We found that SMRP detection in MPM-PE can help the diagnosis of MPM and provide additional diagnostic value to cytology. We concluded that SMRP test may be incorporated into clinical practice of PE from patients suspicious for MPM.
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Biomarcadores de Tumor/metabolismo , Proteínas Ligadas a GPI/metabolismo , Mesotelioma/diagnóstico , Derrame Pleural Maligno/diagnóstico , Neoplasias Pleurales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Citodiagnóstico/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Mesotelina , Mesotelioma/metabolismo , Mesotelioma/patología , Persona de Mediana Edad , Péptidos/metabolismo , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patología , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patologíaRESUMEN
PURPOSE: Programmed death-ligand 1 (PD-L1) protein plays a central role in the antitumor immune response, and appears to be a predictor of prognosis and efficacy for PD-L1 and programmed death 1 (PD-1) blockade therapy. The immunoregulatory role and prognostic impact of PD-L1 soluble form (sPD-L1) have been investigated in biological fluids of patients with different tumors. In malignant pleural mesothelioma (MPM), circulating sPD-L1 has been recently reported in patients' sera, but no data are available in pleural effusions (PE). In our study, we evaluated the baseline expression levels of sPD-L1 in PE from 84 MPM patients and correlated them with PD-L1-status in matched tumors and patients' overall survival (OS). METHODS: sPD-L1 in PE was determined by ELISA and tumor PD-L1 by immunohistochemistry. Association of sPD-L1 with OS was estimated using the Cox regression model. RESULTS: We observed that sPD-L1 was variably expressed in all the PE and tended to be higher (by 30%) in patients with PD-L1-positive tumors (cut-off ≥ 1% stained cells) as compared to patients with PD-L1-negative tumors (geometric mean ratio = 1.28, P value = 0.288). sPD-L1 levels were significantly higher than those of sPD-1 (P value = 0.001) regardless of the MPM histotypes and they were positively correlated (r = 0.50, P value < 0.001). Moreover, high PE sPD-L1 concentrations were associated with a trend towards increased OS (hazard ratio 0.79, 95% CL 0.62-1.01, P value = 0.062). CONCLUSIONS: Our study documents the presence of sPD-L1 in PE of MPM patients, and suggests its possible biological and prognostic role in MPM.
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Antígeno B7-H1/fisiología , Mesotelioma Maligno/inmunología , Derrame Pleural/metabolismo , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Mesotelioma Maligno/mortalidad , Persona de Mediana Edad , Pronóstico , Receptor de Muerte Celular Programada 1/análisis , Modelos de Riesgos ProporcionalesRESUMEN
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor survival rates. Therefore, it is essential to have effective biological markers predicting the course of the disease and prognosis. The aim of the present study was to highlight the prognostic significance of serum soluble mesothelin-related protein (Se-SMRP) in patients with MPM at diagnosis. Se-SMRP was determined in 60 patients using an ELISA commercial kit. Se-SMRP levels were subdivided into three tertile-based categories and in each category overall survival (OS) indexes were determined using the Kaplan-Meier and Cox regression analyses. The association between Se-SMRP levels and OS was also assessed by restricted cubic spline (RCS) analysis. No notable differences in the Kaplan-Meier probabilities were identified across the Se-SMRP categories (<0.66 nM, 0.66-1.46 nM, >1.46 nM) although an upward trend in death rate ratios (RR) was pointed out by comparing the higher (RR=1.95) and intermediate (RR=1.86) categories with the lower category (RR=1.00). In addition, such an increasing tendency, particularly when the biomarker exceeded 1.0 nM, was confirmed by an RCS function of Se-SMPR levels fitted to survival data using the Cox regression equation. The present study provided evidence in favor of a prognostic value of Se-SMRP in patients with MPM.
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Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mostly attributable to asbestos exposure. Many polymorphic genes encoding for xenobiotic and oxidative metabolism enzymes (XME) or involved in genome stability (GS) can modulate individual MPM risk in exposed populations. An association study was carried out in a case-control setting including 119 MPM patients and two groups of referent subjects (104 with and 695 without documented asbestos exposure). Forty-eight polymorphisms in XME genes and 75 in GS-genes were evaluated. Statistical analysis revealed some significant associations of studied polymorphisms with MPM risk, but most of them disappeared after applying Bonferroni correction (new threshold for statistical significance: p=4.07 x 10(-4)). On the other hand, the nucleotidic change 282C>T within NAT2 held the statistical significance (OR=3.54; 95% CI 1.75-7.16; p=0.0002), reinforcing existing evidences that describe genetic polymorphisms of NAT2 possibly involved in the etiology of the MPM.
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Inestabilidad Genómica , Mesotelioma/enzimología , Mesotelioma/genética , Neoplasias Pleurales/enzimología , Neoplasias Pleurales/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Xenobióticos/metabolismoRESUMEN
AIM: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). PATIENTS AND METHODS: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan-Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. RESULTS: No significant differences in Kaplan-Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. CONCLUSION: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.
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Proteínas Ligadas a GPI/metabolismo , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Mesotelioma/complicaciones , Mesotelioma/mortalidad , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/mortalidad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelina , Mesotelioma/diagnóstico , Mesotelioma/terapia , Mesotelioma Maligno , Persona de Mediana Edad , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapia , Pronóstico , Curva ROC , Resultado del TratamientoRESUMEN
OBJECTIVES: The Cancer of RESpiratory Tract (CREST) biorepository was established to investigate biological mechanisms and to develop tools and strategies for primary and secondary prevention of respiratory tract cancer. The CREST biorepository is focused on pleural malignant mesothelioma, a rare and severe cancer linked to asbestos exposure whose incidence is particularly high in the Ligurian region. METHODS: The CREST biorepository includes biological specimens from (a) patients with pleural malignant mesothelioma and lung cancer, (b) patients with nonneoplastic respiratory conditions, and (c) control subjects. Whole blood, plasma, serum, lymphocytes, pleural fluid, saliva, and biopsies are collected, and a questionnaire is administered. Collection, transportation, and storage are done according to international standards. RESULTS: As of January 31, 2008, the overall number of subjects recruited was 1,590 (446 lung cancer, 209 pleural malignant mesothelioma, and 935 controls). The biorepository includes a total of 10,055 aliquots (4,741 serum; 3,082 plasma; 1,599 whole blood; 633 pleural fluid; and 561 lymphocytes) and 107 biopsies. Demographic, clinical, and epidemiologic information is collected for each subject and processed in a dedicated database. CONCLUSIONS: The CREST biorepository is a valuable tool for molecular epidemiology and translational studies. This structure relies on a network of contacts with local health districts that allows for an active search for patients. This is a particularly efficient approach, especially when the object of the study is a rare cancer type. The CREST experience suggests that the presence of limited resources can be overcome by the biorepository specialization, the high quality of the epidemiologic information, and the variety of samples.
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Mesotelioma/epidemiología , Epidemiología Molecular , Neoplasias Pleurales/epidemiología , Bancos de Tejidos , Biomarcadores de Tumor/análisis , Humanos , Consentimiento Informado , Italia/epidemiología , Mesotelioma/genética , Neoplasias Pleurales/genética , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/genética , Encuestas y Cuestionarios , Bancos de Tejidos/éticaRESUMEN
The present study investigates the diagnostic significance of human mammaglobin (hMAM) mRNA expression in pleural effusions (PE) from breast cancer (BC) patients. Two hundred and fifty PE samples, including 32 from patients who had diagnosis of BC, 116 from patients with other cancers, and 102 from patients with benign diseases, were subjected to nested reverse-transcription polymerase chain reaction (RT-PCR) for hMAM, and the results were compared with conventional cytology. hMAM was found expressed in 76/250 (30.4%) total PE and in 23/28 (sensitivity of 82.1%) of the PE subgroup owing to metastasis from BC. The specificity for hMAM detection method was 75.7%, whereas accuracy, positive predictive value, and negative predictive value were 76.4%, 30.3%, and 97.1%, respectively. hMAM was also detected in 46/116 (39.6%) PE specimens from other types of cancer and in 7/102 (6.8%) from benign diseases. Comparative analysis of RT-PCR and cytology showed that 14 PE samples from metastatic BC (50%) were positive by both PCR and cytology, 9 (32.1%) were positive only by PCR and 5 (17.9%) were negative by both tests, whereas no cases were found of positive cytology with negative PCR. RT-PCR increased sensitivity of BC effusion detection to 32.1% (McNemar test, P=0.004). We demonstrated that RT-PCR for hMAM test was more sensitive than cytomorphology suggesting that, although hMAM is not BC specific, it may be useful in adjunct to cytology for the routine screening of malignant BC effusions.
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Neoplasias de la Mama/diagnóstico , Carcinoma/diagnóstico , Proteínas de Neoplasias/análisis , Derrame Pleural Maligno/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Uteroglobina/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma/complicaciones , Carcinoma/genética , Carcinoma/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Mamoglobina A , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/patología , ARN Mensajero/metabolismo , Sensibilidad y Especificidad , Células Tumorales Cultivadas , Uteroglobina/genéticaRESUMEN
PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
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Neoplasias Pulmonares/sangre , Glicoproteínas de Membrana/sangre , Mesotelioma/sangre , Anciano , Femenino , Proteínas Ligadas a GPI , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelina , Mesotelioma/mortalidad , Persona de Mediana Edad , Pronóstico , Enfermedades Respiratorias/sangreRESUMEN
BACKGROUND: In the literature, there exist conflicting data on the value of fibulin-3 (FBLN3) for the diagnosis of pleural effusion (PE) in malignant pleural mesothelioma (MPM). Therefore we compared the diagnostic performance of FBLN3 against that of soluble mesothelin-related peptide (SMRP) in a cohort of Italian patients. MATERIALS AND METHODS: FBLN3 and SMRP were detected in PE from 33 patients with MPM, 64 with pleural benign lesions and 23 with non-MPM pleural metastases using a commercial enzyme-linked-immunosorbent(ELISA)-assay kit according to manufacturers' instructions. RESULTS: Levels of FBLN3 were similar in PE from MPM and PE from other pathologies (geometric mean=68.1 vs. 66.2 ng/ml; p=0.872) in contrast to SMRP levels, which were significantly higher in PE from MPM (geometric mean=14.6 vs. 3.2 nM; p<0.001). Receiver operating characteristic analysis confirmed that SMRP showed a good performance (area under the curve=0.79, p<0.001), whereas FBLN3 was not able to discriminate MPM from other pathologies (area under the curve=0.44, p=0.838). CONCLUSION: FBLN3 detection in PE, in contrast to SMRP detection, is not useful as a biomarker for the diagnosis of PE from MPM.
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Proteínas de la Matriz Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurales/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Italia , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Derrame Pleural Maligno/patología , Neoplasias Pleurales/patología , Curva ROCRESUMEN
We evaluated the frequency of micronuclei (MN) in peripheral blood lymphocytes of patients with pleural malignant mesotelioma (MM), lung cancer, benign respiratory diseases, and healthy controls. A significant increased frequency of MN was observed in patients with MM in comparison with all the other groups (median, 11.4 binucleated MN/1000 binucleated cells versus 5.1, 6.1, and 6.2, respectively). No association was found between MN and asbestos exposure. Recently, genetic susceptibility associated with asbestos exposure has been recognized in the development of MM. The presence of high frequency of MN in peripheral blood lymphocytes of patients with MM could represent a useful index of individual susceptibility to this tumor.
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Linfocitos/ultraestructura , Mesotelioma/genética , Micronúcleos con Defecto Cromosómico , Amianto/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Masculino , Mesotelioma/sangre , Exposición Profesional , Neoplasias Pleurales/sangre , Neoplasias Pleurales/genéticaRESUMEN
Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. In this work we performed a comparative proteomic analysis of biphasic pleural mesothelioma (B-PM). Tissue biopsies were obtained from 61 patients who were subjected to a diagnostic thoracoscopy. 2D/MS based approach was used for proteomic analysis. The 22 proteins found differentially expressed in B-PM, with respect to benign, were analyzed by Ingenuity Pathways Analysis and compared with those obtained for epitheliod pleural mesothelioma (E-PM). A different activation of transcription factors, proteins and cytokines were observed between two subtypes.
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OBJECTIVE:: To evaluate the correlation between apparent diffusion coefficient (ADC) values and histopathological features in a cohort of patients with suspected malignant pleural disease. METHODS:: We evaluated 56 consecutive patients undergoing a chest MRI examination for clinical suspicion of malignant pleural disease; all patients underwent thoracoscopic biopsy for histological assessment. All MRI examinations were performed with a 1.5-T scanner using a dedicated protocol, including a respiratory-triggered diffusion-weighted sequence with three b-values (0, 100 and 750). The ADC values were calculated, and a statistical analysis was performed. RESULTS:: The average ADC value in non-neoplastic pleural disease (NNPD) resulted in 1.84 ± 0.37 × 10-3 mm2 s-1, whereas we obtained an average value of 0.96 ± 0.19 × 10-3 mm2 s-1 in epitheliod, of 0.76 ± 0.33 × 10-3 mm2 s-1 in biphasic and of 0.67 ± 0.2 × 10-3 mm2 s-1 in sarcomatoid pleural mesotheliomas. Histology revealed the presence of malignant pleural mesothelioma (MPM) in 44 patients, chronic pleuritis in 8 patients and atypical mesothelial hyperplasia in 4 patients. Statistical analysis showed a significant difference between NNPD and MPM (p < 0.001) and between epithelioid and sarcomatoid MPM subtypes (p = 0.0004), whereas biphasic MPMs showed a wide range of overlapping with the other groups. CONCLUSION:: We observed a statistically significant difference between NNPD, epitheliod and sarcomatoid subtypes of MPM regarding ADC values. ADVANCES IN KNOWLEDGE:: Our study confirmed previous data regarding distribution of ADC values in pleural disease using a respiratory-triggered diffusion-weighted technique that allowed us to minimize motion artefacts and to reduct acquisition time.
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Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.
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Amianto/efectos adversos , Predisposición Genética a la Enfermedad , Mesotelioma/genética , Neoplasias Pleurales/genética , ADN/sangre , ADN/genética , ADN/aislamiento & purificación , Exposición a Riesgos Ambientales , Genotipo , Glutatión Transferasa/genética , Humanos , Isoenzimas/genética , Mesotelioma/etiología , Pruebas de Micronúcleos , Neoplasias Pleurales/etiologíaAsunto(s)
Biomarcadores de Tumor/sangre , Proteínas Ligadas a GPI/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Mesotelioma/sangre , Mesotelioma/patología , Neoplasias Pleurales/sangre , Neoplasias Pleurales/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Mesotelina , Mesotelioma MalignoRESUMEN
BACKGROUND: Malignant mesothelioma (MM) is a particularly aggressive type of primary tumor, associated with exposure to asbestos, and characterized by high mortality. To date, there is no curative therapy for MM. The receptor anaplastic lymphoma kinase (ALK) was found to be mutated in many cases of cancer and used as a target in biological therapies. We investigated whether this pharmacological treatment could also be applicable to MM. MATERIALS AND METHODS: The state of ALK was analyzed by immunohistochemistry and fluorescent in situ hybridization in 63 MM tissue specimens. RESULTS: None of the 63 MM samples showed overexpression or translocation of ALK. CONCLUSION: Our preliminary data exclude the utility of analysis of the ALK gene in MM and suggest that ALK inhibitor therapy is not applicable to MM.
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Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Mesotelioma/enzimología , Mesotelioma/genética , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Proteínas Tirosina Quinasas Receptoras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Mesotelioma Maligno , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
BACKGROUND/AIM: Mesothelin (SMRP) is regarded as a biomarker of malignant pleural mesothelioma (MPM). Herein, we analyzed the contribution of SMRP detection in pleural effusion and in serum to the diagnosis of MPM with non-positive cytology. MATERIALS AND METHODS: The present study included 52 cases of MPM, 43 of pleural benign lesions and 25 of non-MPM pleural metastases. SMRP was measured by MesoMark ELISA (Cis-Bio International Gif/Yvette; France). RESULTS: In non-positive cytology, effusion-SMRP showed higher diagnostic performance than serum-SMRP. We found 38 out of 52 (73.1%) cases of non-positive cytology MPM, out of which 27 (71.0%) were positive for effusion-SMRP (cut-off=12.70 nM) and 18 (47.4%) for serum-SMRP (cut-off=1.08 nM). When cytology, effusion- and serum-SMRP were used in combination, an overall sensitivity in detection of MPM of 78.9% was achieved. The same sensitivity was obtained by combining cytology with effusion-SMRP alone, whereas the combination of serum-SMRP with cytology led to a sensitivity of 61.5%. CONCLUSION: Detection of both effusion- and serum-SMRP can contribute to improve the diagnosis of MPM with non-positive cytology. However, the analysis of SMRP in effusion makes it unnecessary to test SMRP in the serum.
Asunto(s)
Biomarcadores de Tumor/sangre , Proteínas Ligadas a GPI/sangre , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Derrame Pleural/patología , Neoplasias Pleurales/diagnóstico , Anciano , Anciano de 80 o más Años , Asbestosis/sangre , Citodiagnóstico , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Mesotelina , Mesotelioma/sangre , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pleurales/sangre , Neoplasias Pleurales/patologíaRESUMEN
The aim of this study based on the third phase of the architecture of diagnostic research was to assess the sensitivity and specificity of soluble mesothelin-related peptide (SMRP) in pleural exudative effusions (PE) compared to the histology obtained by medical thoracoscopy as the diagnostic gold standard examination. We assessed 104 consecutive thoracoscopies. SMRP concentrations were obtained using an ELISA test. We had 34 mesotheliomas (25 epithelioid and 9 sarcomatoid), 35 pleural metastases, and 35 benign diseases. PE-SMRP were significantly higher in patients with epitheliomorphic mesothelioma (mean ± SD 46.55 ± 44.29 nM) than in patients with sarcomatoid mesothelioma (16.11 ± 25.02 nM; p = 0.061), pleural metastasis (7.52 ± 10.77 nM; p < 0.0001), or benign diseases (5.82 ± 8.86 nM; p < 0.0001). Using ROC curve analysis, PE-SMRP offered an AUC of 0.767 in its ability to differentiate between patients with mesothelioma and all other diagnoses. The diagnostic sensitivity and specificity of PE-SMRP for distinguishing mesothelioma from all other causes of pleural effusion, at a cut-off value of 19.6 nM, were 58.8 and 97.1 %, respectively. PE-SMRP higher than the assumed cut-off of 19.6 nM were observed in 18/25 (72.0%) epitheliomorphic mesotheliomas, 2/9 (22.2%) sarcomatoid mesotheliomas, 5/35 (14.3%) pleural metastases, and 1/35 (2.9%) benign diseases. We conclude that PE-SMRP adds some clinical information in the work-up of patients with a PE of unknown origin: (1) thoracoscopy should always be done in patients with a positive mesothelin; (2) a negative mesothelin does not exclude a malignant disease.