Riassunto
Premesse
Il Mesotelioma pleurico (MPM) è un tumore molto aggressivo frequentemente associato alla comparsa di un versamento pleurico (MPM-VP). La diagnosi differenziale del MPM-VP viene effettuata mediante citologia, ma spesso risulta difficile. Lo scopo del presente lavoro è di valutare il contributo che la determinazione del livello di Mesotelina (MS) nel VP può offrire all’analisi citologica nella pratica clinica.
Metodi
La MS è stata determinata mediante il Kit Elisa Mesomark™ su un’aliquota di VP estratto mediante toracentesi. La citologia è stata valutata su strisci fissati e colorati con metodo Papanicolau.
Risultati
Nello studio sono stati arruolati 52 pazienti affetti da MPM e 223 con patologia diversa da MPM. La media geometrica del livello della MS era significativamente più elevata nei MPM-VP (19,0 nmol/L) che negli altri VP (1,2 nmol/L). Il livello di cut-off era stimato in 9,30 nmol/L con AUC=0,82, Sensibilità=75,0% e Specificità=87,9%. Valori di MS ≥cut-off erano trovati in 38/52 (73%) dei MPM-VP vs 27/223 (12%) degli altri VP (DOR=21,8; Pearson chi square test P-value <0,001).
In 5/23 (21,7%) dei MPM-VP citologia-positivi o sospetti positivi il livello di MS non confermava la diagnosi. Al contrario in 20/29 (69,0%) casi di MPM citologia-negativi, il valore di MS risultava positivo.
Conclusioni
La determinazione della MS nel VP può essere un valore aggiunto alla citologia per definire la diagnosi di MPM e può essere un test impiegabile nella pratica clinica nella diagnosi dei VP che insorgono in pazienti con sospetto MPM.
Summary
Background
Malignant pleural mesothelioma (MPM) is an aggressive tumour usually associated with the presence of pleural effusion (PE). Differential diagnosis of the PE can be difficult because cytological analysis shows low sensitivity and specificity. Measurement of solubile mesothelin peptides (MS) has been reported to provide a complementary tool to aid in the diagnosis of MPM.
The current study was undertaken to assess whether the levels of MS in PE may provide an additional diagnostic value to cytology and clinical practice.
Methods
MS was assessed by means of the MesoMark™ ELISA kit on a fraction of PE extracted by thoracentesis. Cytology was evaluated on fixed smears stained by Papanicolaou’s method.
Results
We evaluated MS in 52 MPM-PE and 223 PE of other origin. The geometric mean of MS levels in PE was significantly higher in MPM-PE (19.0 nmol/L) than in total other PE (3.5 nmol/L). The cut-off level was 9.30 nmol/L with an AUC of 82.0 (P-value <0.001), Sensitivity=75% and Specificity=87%. We found MS positive cases (-cut-off) in 38/52 (73%) of MPM-PE and MS in 27/223 (12%) of other PE (DOR 21.8; Pearson chisquare test P-value <0.001).
Moreover, in the 5/23 (21.7%) cytology positive/suspicious MPM-PE the levels of SMRP were <9.30 nmol/L (cut-off). In contrast, in the 20/29 (69.0%) MPM-PE in which cytology was found negative the MS levels resulted positive.
Conclusions
MS detection in MPM-PE may provide additional diagnostic value to cytology. The MS test may be incorporated into clinical practice of PE from patients suspicious for MPM.
Bibliografia
Herndon JE, Green MR, Chahinian AP et al (1998) Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B. Chest 113:723–731
Aziz T, Jilaihawi A, Prakash D (2002) The management of malignant pleural mesothelioma; single centre experience in 10 years. Eur J Cardiothorac Surg 22:298–305
Borasio P, Berruti A, Billé A et al (2008) Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients. Eur J Cardiothorac Surg 33:307–313.
Wagner JC, Sleggs CA, Marchand P (1960) Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 17:260–271
Marinaccio A, Binazzi A, Di Marzio D et al (2001) Il registro Nazionale dei Mesoteliomi: risultati, interpretazione, commento ai dati. In: Il registro Nazionale dei Mesoteliomi. Terzo rapporto. Istituto Superiore per la Prevenzione e la Sicurezza del lavoro 27–34
Costa D, Guignard J, Zalma R et al (1989) Production of free radicals arising from the surface activity of minerals and oxygen. Part I. Iron mine ores. Toxicol Ind Health 5:1061–1078
Shannon VR, Nesbitt JC, Libshitz HI (1995) Malignant pleural mesothelioma after radiation therapy for breast cancer. A report of two additional patients. Cancer 76:437–441
Goodman JE, Nascarella MA, Valberg PA (2009) Ionizing radiation: a risk factor for mesothelioma. Cancer Causes Control 20:1237–1254
Hillerdal G, Berg J (1985) Malignant mesothelioma secondary to chronic inflammation and old scars. Two new cases and review of the literature. Cancer 55:1968–1972
Pass HI, Bocchetta M, Carbone M (2004) Evidence of an important role for SV40 in mesothelioma. Thorac Surg Clin 14:489–495
Dawson A, Gibbs A, Browne K et al (1992) Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis. Cancer 70:1183–1187
Muscat JE, Wynder EL (1991) Cigarette smoking, asbestos exposure, and malignant mesothelioma. Cancer Res 51:2263–2267
Fazzo L, De Santis M, Minelli G et al (2012) Pleural mesothelioma mortality and asbestos exposure mapping in Italy. Am J Ind Med 55:11–24
Larson T, Melnikova N, Davis SI et al (2007) Incidence and descriptive epidemiology of mesothelioma in the United States, 1999–2002. Int J Occup Environ Health 13:398–403
Gennaro V, Ugolini D, Viarengo P et al (2005) Incidence of pleural mesothelioma in Liguria Region, Italy (1996–2002). Eur J Cancer 41:2709–2714
Light RW (2006) The undiagnosed pleural effusion. Clin Chest Med 27:309–319
Renshaw AA, Dean BR, Antman KH et al (1997) The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Chest 111:106–109
Metintas M, Ak G, Dundar E et al (2010) Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis of patients with pleural effusions: a randomized, controlled trial. Chest 137:1362–1368
Rakha EA, Patil S, Abdulla K et al (2010) The sensitivity of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Diagn Cytopathol 38:874–879
Ray M, Kindler HL (2009) Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest 136:888–896
Grigoriu BD, Grigoriu C, Chahine B et al (2009) Clinical utility of diagnostic markers for malignant pleural mesothelioma. Monaldi Arch Chest Dis 71:31–38
Roncella S, Ferro P, Franceschini MC et al (2010) Diagnosis and origin determination of malignant pleural effusions through the use of the breast cancer marker human mammaglobin. Diagn Mol Pathol 19:92–98
Carletti AM, Roncella S, Canessa PA et al (2006) Expression of human mammaglobin gene in pleural effusions of patients with malignant mesothelioma. Thorax 61:271
Chang K, Pastan I (1996) Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA 93:136–140
Chang K, Pai LH, Pass H et al (1992) Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. Am J Surg Pathol 16:259–268
Ordóñez NG (2003) Value of mesothelin MPM immunostaining in the diagnosis of mesothelioma. Mod Pathol 16:192–197
Beyer HL, Geschwindt RD, Glover CL et al (2007) MESOMARK: a potential test for malignant pleural mesothelioma. Clin Chem 53:666–672
Cristaudo A, Foddis R, Vivaldi A et al (2007) Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer. Clin Cancer Res 13:5076–5081
Robinson BW, Creaney J, Lake R et al (2003) Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 36:1612–1606
Wheatley-Price P, Yang B, Patsios D et al (2010) Soluble mesothelin-related Peptide and osteopontin as markers of response in malignant mesothelioma. J Clin Oncol 28:3316–3322
Alemán C, Porcel MJ, Ma Segura R et al (2009) Pleural fluid mesothelin for the differential diagnosis of exudative pleural effusions. Med Clin (Barc) 133:449–453
Scherpereel A, Grigoriu B, Conti M et al (2006) Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. Am J Respir Crit Care Med 173:1155–1160
Creaney J, Yeoman D, Naumoff NK et al (2007) Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma. Thorax 62:569–576
Pass HI, Wali A, Tang N et al (2008) Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions. Ann Thorac Surg 85:265–272
Davies HE, Sadler RS, Bielsa S et al (2009) Clinical impact and reliability of pleural fluid mesothelin in undiagnosed pleural effusions. Am J Respir Crit Care Med 180:437
Yamada S, Tabata C, Tabata R et al (2011) Clinical significance of pleural effusion mesothelin in malignant pleural mesothelioma. Clin Chem Lab Med 49:1721–1726
Glas AS, Lijmer JG, Prins MH et al (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56:1129–1135
Pepe MS (2003) The Statistical Evaluation of Medical Tests for Classification and Prediction. Oxford, UK: Oxford University Press
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Battolla, E., Canessa, P.A., Ferro, P. et al. Determinazione della Mesotelina nel versamento pleurico: contributo alla citologia nella diagnosi del Mesotelioma pleurico maligno. Riv Ital Med Lab 8, 94–100 (2012). https://doi.org/10.1007/s13631-012-0047-y
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DOI: https://doi.org/10.1007/s13631-012-0047-y