Abstract
There are no published studies examining the utility of total homocysteine (HCY) in pleural fluid. The aim was to measure the accuracy of pleural fluid HCY concentration for diagnosis of malignant pleural effusion (MPE). We studied pleural fluids obtained by thoracocentesis in patients with pleural effusion. Pleural fluid HCY concentration was measured by immunonephelometry using N Latex HCY reagent with monoclonal antibody in automated analyzers BNII (Siemens Diagnostics®). Patients were classified into two groups according to the etiology of pleural effusion: benign pleural effusions (BPE) and MPE. Pleural effusion was categorized as MPE if malignant cells were demonstrated in pleural fluid or pleural biopsy. The accuracy of pleural fluid HCY concentration for diagnosis of MPE was determined using receiver operating characteristic (ROC) techniques by analyzing the area under the ROC curve (AUC). We studied 89 patients with ages between 1 and 96 years old (median = 66). Forty-eight patients were BPE and 41 were MPE. Pleural fluid HCY concentration was significantly higher in patients with MPE (median = 13.70 μmol/L) than in those with BPE (median = 8.05 μmol/L). The AUC value was 0.833 (95 % confidence interval (CI) 0.739–0.903). The optimal cutoff value was 13.1 μmol/L exhibiting 56.1 % (95 % CI 39.8–71.5) sensitivity and 85.4 % (95 % CI 72.2–93.9) specificity. Pleural fluid HCY concentration showed high diagnostic accuracy to predict whether a pleural effusion is benign or malignant. Pleural fluid HCY concentration may be measured easily and quickly in automated analyzers and could be a tumor marker commonly used for diagnosis of MPE.
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References
Thomas JM, Musani AI. Malignant pleural effusions: a review. Clin Chest Med. 2013;34:459–71.
Egan AM, McPhillips D, Sarkar S, Breen DP. Malignant pleural effusion. QJM. 2014;107:179–84.
Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ. BTS Pleural Disease Guideline Group. management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65:32–40.
Ruckdeschel JC. Management of malignant pleural effusions. Semin Oncol. 1994;22:58–63.
Rodriguez-Panadero F, Naranjo FB, Lopez-Mejias J. Pleural metastatic tumours and effusions. frequency and pathogenic mechanisms in a postmortem series. Eur Respir J. 1989;2:366–9.
Li D, Wang B, Hu Q, Shen Y, Xu D, Wang T, et al. Diagnostic accuracy of MOC-31 for malignant effusions: a meta-analysis. Tumour Biol. 2014;35:6003–9.
Wang Y, Chen Z, Chen J, Pan J, Zhang W, Pan Q, et al. The diagnostic value of apolipoprotein E in malignant pleural effusion associated with non-small cell lung cáncer. Clin Chim Acta. 2013;421:230–5.
Trapé J, Molina R, Sant F. Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions. Tumor Biol. 2004;25:276–81.
Mudd SH, Levy HL, Skorby F. Disorder of transulfuración. In: Scriber CR, Beaudet AL, Sly WS, Valle D, Eds. The metabolic and molecular bases of inherited disease, 7th ed. New York Mc Graw-Hill, 1995:1229–327.
Fiskerstrand T, Refsum H, Koalheim G, Ueland PM. Homocysteine and other tiols in plasma and urine: automated determination and sample stability. Clin Chem. 1993;39:263–71.
Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, et al. A prospective study of plasma homocysteine and risk of myocardial infarction in US physicians. JAMA. 1992;268:877–81.
Selhub J, Jacques PF, Bostom AG, D’Agostino RB, Wilson PW, Belanger AJ, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med. 1995;332:286–91.
Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 1995;346:1395–8.
Zacho J, Yazdanyar S, Bojesen SE, Tybjærg-Hansen A, Nordestgaard BG. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C > T polymorphism, and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls. Int J Cancer. 2011;128:644–52.
Ferroni P, Palmirotta R, Martini F, Riondino S, Savonarola A, Spila A, et al. Determinants of homocysteine levels in colorectal and breast cancer patients. Anticancer Res. 2009;29:4131–8.
Nurk E, Refsum H, Tell GS, Engedal K, Vollset SE, Ueland PM, et al. Plasma total homocysteine and memory in the elderly: the Hordaland Homocysteine Study. Ann Neurol. 2005;58:847–57.
Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr. 2005;82:636–43.
den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, et al. Homocysteine and brain atrophy on MRI of non-demented elderly. Brain. 2003;126:170–5.
Choe YM, Sohn BK, Choi HJ, Byun MS, Seo EH, Han JY, et al. Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden. Neurobiol Aging. 2014;35:1519–25.
Heffner JE, Klein JS. Recent advances in the diagnosis and management of malignant pleural effusions. Mayo Clin Proc. 2008;83:235–50.
Xu CH, Zhan P, Yu LK, Zhang XW. Diagnostic value of pleural interleukin 17 and carcinoembryonic antigen in lung cancer patients with malignant pleural effusions. Tumour Biol. 2014;35:1599–603.
Ferreiro L, Toubes ME, Valdés L. Contribution of pleural fluid analysis to the diagnosis of pleural effusion. Med Clin (Barc) 2014 Nov 26.
Santotoribio JD, Sánchez-Linares P, Cabrera-Alarcón JL, Guerrero JM. Diagnostic value of carcinoembryonic antigen measurement in pleural fluid. Med Clin (Barc). 2010;135:574–5.
Trapé J, Molina R, Sant F, Montesinos J, Arnau A, Franquesa J, et al. Diagnostic accuracy of tumour markers in serous effusions: a validation study. Tumour Biol. 2012;33:1661–8.
Santotoribio JD, Delgado-Pecellín C, León-Justel A, Guerrero JM. Treatment indication with endothoracic drainage tube in parapneumonic effusions by partial pressure of carbon dioxide measurement in pleural fluid. Med Clin (Barc). 2008;131:130–3.
Santotoribio JD, León-Justel A, Delgado-Pecellín C, Guerrero JM. What are the biochemical parameters of pleural fluid that best identify parapneumonic effusions? Ann Clin Biochem. 2009;46:176–7.
Elsammak MY, Attia A, Hassan HA, Zaytoun TM, Shorman M, Suleman M. Evaluation of pleural fluid human epididymis 4 (HE4) as a marker of malignant pleural effusion. Tumour Biol. 2012;33:1701–7.
Trapé J, Molina R, Sant F, Montesinos J, Arnau A, Franquesa J, et al. Diagnostic accuracy of tumour markers in serous effusions: a validation study. Tumour Biol. 2012;33:1661–8.
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;63:35–41.
Hsi HZ, Liang QL, Jiang J, Qin XJ, Yang HB. Diagnostic value of carcinoembryonic antigen in malignant pleural effusion: a meta-analysis. Respirology. 2008;13:518–27.
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Santotoribio, J.D., Cañavate-Solano, C., Garcia-de la Torre, A. et al. Homocysteine: new tumor marker in pleural fluid. Tumor Biol. 36, 7941–7945 (2015). https://doi.org/10.1007/s13277-015-3517-9
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DOI: https://doi.org/10.1007/s13277-015-3517-9