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Semin Respir Crit Care Med 2019; 40(03): 340-346
DOI: 10.1055/s-0039-1695702
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Molecular Testing on Pleural Fluid Samples

Scott Oh
1   Division of Pulmonary, Critical Care Medicine, Clinical Immunology, and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, California
,
Reza Ronaghi
1   Division of Pulmonary, Critical Care Medicine, Clinical Immunology, and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, California
,
Guoping Cai
2   Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
16 September 2019 (online)

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Abstract

Pleural effusions are a common manifestation of both malignant and nonmalignant diseases. The sampling of pleural fluid helps categorize effusions as transudative or exudative and helps differentiate paramalignant from malignant disease. Accurate pleural fluid analysis is critical to the appropriate staging of cancers with significant prognostic and treatment implications. However, the etiology of pleural effusions remains unclear in a significant number of cases after routine thoracentesis and pleural fluid analysis. For malignant pleural effusions, cytologic evaluation of pleural fluid has a relatively low sensitivity. We describe the evolving field of molecular pleural fluid analysis in the setting of malignant disease as an active area of investigation with both diagnostic and therapeutic implications.

Keywords

malignant pleural effusion - molecular testing - pleural fluid analysis
 

  • References

  • 1 Porcel JM, Vives M, Esquerda A, Salud A, Pérez B, Rodríguez-Panadero F. Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest 2004; 126 (06) 1757-1763
    CrossrefPubMedGoogle Scholar
  • 2 The American Thoracic Society and The European Respiratory Society. Pretreatment evaluation of non-small-cell lung cancer. Am J Respir Crit Care Med 1997; 156 (01) 320-332
    CrossrefPubMedGoogle Scholar
  • 3 Sahn SA. Pathogenesis and clinical features of diseases associated with a low pleural fluid glucose. In: The Pleura in Health and Disease. Chretien J, Bignon J, Hirsch A. eds. New York, NY: Marcel Dekker; 1985: 267-285
    Google Scholar
  • 4 Agarwal R, Aggarwal AN, Gupta D. Diagnostic accuracy and safety of semirigid thoracoscopy in exudative pleural effusions: a meta-analysis. Chest 2013; 144 (06) 1857-1867
    CrossrefPubMedGoogle Scholar
  • 5 Rooper LM, Ali SZ, Olson MT. A minimum fluid volume of 75 mL is needed to ensure adequacy in a pleural effusion: a retrospective analysis of 2540 cases. Cancer Cytopathol 2014; 122 (09) 657-665
    PubMedGoogle Scholar
  • 6 Swiderek J, Morcos S, Donthireddy V. , et al. Prospective study to determine the volume of pleural fluid required to diagnose malignancy. Chest 2010; 137 (01) 68-73
    CrossrefPubMedGoogle Scholar
  • 7 Abouzgheib W, Bartter T, Dagher H, Pratter M, Klump W. A prospective study of the volume of pleural fluid required for accurate diagnosis of malignant pleural effusion. Chest 2009; 135 (04) 999-1001
    CrossrefPubMedGoogle Scholar
  • 8 Garcia LW, Ducatman BS, Wang HH. The value of multiple fluid specimens in the cytological diagnosis of malignancy. Mod Pathol 1994; 7 (06) 665-668
    PubMedGoogle Scholar
  • 9 Bielsa S, Panadés MJ, Egido R. , et al. Accuracy of pleural fluid cytology in malignant effusions [in Spanish]. Med Interna 2008; 25 (04) 173-177
    PubMedGoogle Scholar
  • 10 Heffner JE, Brown LK, Barbieri CA. ; Primary Study Investigators. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Chest 1997; 111 (04) 970-980
    CrossrefPubMedGoogle Scholar
  • 11 Porcel JM. Biomarkers in the diagnosis of pleural diseases: a 2018 update. Ther Adv Respir Dis 2018; 12: 1-11
    PubMedGoogle Scholar
  • 12 Rehder CW, David KL, Hirsch B, Toriello HV, Wilson CM, Kearney HM. American College of Medical Genetics and Genomics: standards and guidelines for documenting suspected consanguinity as an incidental finding of genomic testing. Genet Med 2013; 15 (02) 150-152
    PubMedGoogle Scholar
  • 13 Shin S, Kim J, Kim Y, Cho SM, Lee KA. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients. Clin Chem Lab Med 2017; 55 (12) 1962-1969
    PubMedGoogle Scholar
  • 14 Isgrò MA, Bottoni P, Scatena R. Neuron-specific enolase as a biomarker: biochemical and clinical aspects. In: Scatena R. ed. Advances in Cancer Biomarkers: From Biochemistry to Clinic for a Critical Revision. Dordrecht: Springer; 2015: 125-143
    Google Scholar
  • 15 Guan Y, Wang ZJ, Wang LQ, Hua DF, Liu J. Comparison of EGFR mutation rates in lung adenocarcinoma tissue and pleural effusion samples. Gen Molecular Res 2016; 15 (02) 1-7
    PubMedGoogle Scholar
  • 16 Billah S, Stewart J, Staerkel G, Chen S, Gong Y, Guo M. EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol 2011; 119 (02) 111-117
    PubMedGoogle Scholar
  • 17 Sahn SA, Good Jr JT. Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications. Ann Intern Med 1988; 108 (03) 345-349
    PubMedGoogle Scholar
  • 18 Ordóñez NG. Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod Pathol 2003; 16 (03) 192-197
    PubMedGoogle Scholar
  • 19 Scherpereel A, Grigoriu B, Conti M. , et al. Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. Am J Respir Crit Care Med 2006; 173 (10) 1155-1160
    CrossrefPubMedGoogle Scholar
  • 20 Creaney J, Yeoman D, Naumoff LK. , et al. Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma. Thorax 2007; 62 (07) 569-576
    CrossrefPubMedGoogle Scholar
  • 21 Pass HI, Levin SM, Harbut MR. , et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med 2012; 367 (15) 1417-1427
    CrossrefPubMedGoogle Scholar
  • 22 Grigoriu BD, Scherpereel A, Devos P. , et al. Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment. Clin Cancer Res 2007; 13 (10) 2928-2935
    CrossrefPubMedGoogle Scholar
  • 23 Chang K, Pai LH, Pass H. , et al. Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. Am J Surg Pathol 1992; 16 (03) 259-268
    CrossrefPubMedGoogle Scholar
  • 24 Davies HE, Sadler RS, Bielsa S. , et al. Clinical impact and reliability of pleural fluid mesothelin in undiagnosed pleural effusions. Am J Respir Crit Care Med 2009; 180 (05) 437-444
    CrossrefPubMedGoogle Scholar
  • 25 Muñoz A, Barceló R, López-Vivanco G. Malignant mesothelioma. N Engl J Med 2006; 354 (03) 305-307 , author reply 305–307
    CrossrefPubMedGoogle Scholar
  • 26 Fukuoka M, Wu YL, Thongprasert S. , et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011; 29 (21) 2866-2874
    CrossrefPubMedGoogle Scholar
  • 27 Spranger S, Spaapen RM, Zha Y. , et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 2013; 5 (200) 200ra116
    PubMedGoogle Scholar
  • 28 DeMaio A, Clarke JM, Dash R. , et al. Yield of malignant pleural effusion for detection of oncogenic driver mutations in lung adenocarcinoma. J Bronchology Interv Pulmonol 2019; 26 (02) 96-101
    CrossrefPubMedGoogle Scholar
  • 29 Xu J, Han X, Liu C. , et al. PD-L1 expression in pleural effusions of pulmonary adenocarcinoma and survival prediction: a controlled study by pleural biopsy. Sci Rep 2018; 8 (01) 11206
    CrossrefPubMedGoogle Scholar
  • 30 Carter J, Miller JA, Feller-Kopman D, Ettinger D, Sidransky D, Maleki Z. Molecular profiling of malignant pleural effusion in the metastatic non small cell lung carcinoma. The effect off preanalytical factors. Ann Am Thorac Soc 2017; 14 (07) 1169-1176
    PubMedGoogle Scholar
  • 31 Lee CK, Davies L, Wu YL. , et al. Gefitinib or erlotinib vs chemotherapy for EGFR mutation-positive lung cancer: individual patient data meta-analysis of overall survival. J Natl Cancer Inst 2017; 109 (06) 1-9
    PubMedGoogle Scholar
  • 32 Liu N, Sun RZ, Du J. , et al. Comparison of epidermal growth factor receptor gene mutations identified using pleural effusion and primary tumor tissue samples in non-small cell lung cancer. Appl Immunohistochem Mol Morphol 2018; 26 (04) e44-e51
    CrossrefPubMedGoogle Scholar
  • 33 Soria JC, Ohe Y, Vansteenkiste J. , et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378 (02) 113-125
    CrossrefPubMedGoogle Scholar
  • 34 Lee H, Deignan JL, Dorrani N. , et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 2014; 312 (18) 1880-1887
    CrossrefPubMedGoogle Scholar
  • 35 Sintchenko V, Holmes EC. The role of pathogen genomics in assessing disease transmission. BMJ 2015; 350: 1-13
    CrossrefPubMedGoogle Scholar
  • 36 Hydbring P, De Petris L, Zhang Y. , et al. Exosomal RNA-profiling of pleural effusions identifies adenocarcinoma patients through elevated miR-200 and LCN2 expression. Lung Cancer 2018; 124: 45-52
    CrossrefPubMedGoogle Scholar
  • 37 Porcel JM, Esquerda A, Martínez-Alonso M, Bielsa S, Salud A. Identifying thoracic malignancies through pleural fluid biomarkers: a predictive multivariate model. Medicine (Baltimore) 2016; 95 (10) e3044
    PubMedGoogle Scholar
  • 38 USC. Available at: https://cancergenome-nih-gov.libproxy1.usc.edu/ . Accessed July 31, 2019
    PubMed
  • 39 Liu L, Shao D, Deng Q. , et al. Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens. J Thorac Dis 2018; 10 (05) 2631-2637
    CrossrefPubMedGoogle Scholar
  • 40 Tseng YH, Ho HL, Lai CR. , et al. PD-L1 expression of tumor cells, macrophages, and immune cells in non-small cell lung cancer patients with malignant pleural effusion. J Thorac Oncol 2018; 13 (03) 447-453
    CrossrefPubMedGoogle Scholar
  • 41 Light RW, Macgregor MI, Luchsinger PC, Ball Jr WC. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77 (04) 507-513
    CrossrefPubMedGoogle Scholar
  • 42 Liang QL, Shi HZ, Qin XJ, Liang XD, Jiang J, Yang HB. Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta-analysis. Thorax 2008; 63 (01) 35-41
    CrossrefPubMedGoogle Scholar
  • 43 Heymann JJ, Bulman WA, Swinarski D. , et al. PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol 2017; 125 (12) 896-907
    CrossrefPubMedGoogle Scholar
  • 44 Lam CW, Law CY. Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions. J Proteome Res 2014; 13 (09) 4040-4046
    CrossrefPubMedGoogle Scholar
  • 45 Zennaro L, Vanzani P, Nicolè L, Cappellesso R, Fassina A. Metabonomics by proton nuclear magnetic resonance in human pleural effusions: a route to discriminate between benign and malignant pleural effusions and to target small molecules as potential cancer biomarkers. Cancer Cytopathol 2017; 125 (05) 341-348
    PubMedGoogle Scholar
  • 46 Zhou XM, He CC, Liu YM. , et al. Metabonomic classification and detection of small molecule biomarkers of malignant pleural effusions. Anal Bioanal Chem 2012; 404 (10) 3123-3133
    CrossrefPubMedGoogle Scholar
  • 47 San Jose ME, Alvarez D, Valdes L, Sarandeses A, Valle JM, Penela P. Utility of tumour markers in the diagnosis of neoplastic pleural effusion. Clin Chim Acta 1997; 265 (02) 193-205
    CrossrefPubMedGoogle Scholar