Increased micronucleus count predicts malignant behavior in pleural effusion fluid

Background/aim: Micronucleus (MN) frequency is used as a biomarker of chromosomal damage, genome instability, and cancer risk.The aim of this study was to evaluate the diagnostic usefulness of MN frequency to differentiate between malignant and benign pleuraleffusion samples.Materials and methods: Retrospectively, 78 pleural fluid cytology samples (including 20 cases of benign reactive mesothelial cells, 22cases of suspicious cytology, and 36 cases of malignant cytology) were examined. The number of micronucleated cells in 1000 wellpreserved cells was counted. Statistical tests were performed to compare the study groups. Recover operating characteristics (ROC)curve analysis was performed to suggest a cut-off value for predicting malignant behavior.Results: We evaluated a total of 78 cases of pleural effusion cytology. The number of micronucleated cells was significantly higher incases with malignant outcome compared to cases with benign outcome. We observed that malignant samples had more micronucleatedcells than suspicious ones, and suspicious cases had more micronucleated cells than reactive ones. There was a significant differenceamong all study groups. In addition, the frequency of MN-containing cells in suspicious cases correlates well with their outcomes.Conclusion: The results of this study reveal that there is an absolute, consistent, and proportional relationship between MN countsand malignancy in cytological samples of pleural effusions. MN scoring may be a helpful diagnostic tool for distinguishing malignanteffusions from benign ones, and may be used as an adjunct tool to predict malignant behavior in challenging cases.

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Iarmarcovai G, Ceppi M, Botta A, Orsière T, Bonassi S. Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis. Mutat Res 2008; 659: 274-283.
Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project—an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res 1999; 428: 271-283.
Samanta S, Dey P. Micronucleus and its applications. Diagn Cytopathol 2011; 40: 84-90.
Stopper H, Muller SO. Micronuclei as a biological endpoint for genotoxicity: a mini review. Toxicol In Vitro 1997; 11: 661-667.
Fisher AH. Diagnostic pathology of the nuclear envelope in human cancers. In: Schirmer EC and de las Heras JI, editors. Cancer Biology and the Nuclear Envelope. New York, NY, USA: Springer, 2014. pp. 49-75.
Mateuca R, Lombaert N, Aka PV, Decordier I, Kirsch-Volders M. Chromosomal changes: induction, detection methods and applicability in human monitoring. Biochimie 2006; 88: 1515- 1531.
Bonassi S, El-Zein R, Bolognesi C, Fenech M. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis 2011; 26: 93-100.
Cagle PT, Churg A. Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies. Arch Pathol Lab Med 2005; 129: 1421-1427.
Churg A, Galateau-Salle F. The separation of benign and malignant mesothelial proliferations. Arch Pathol Lab Med 2012; 136: 1217-1226.
Galateau-Salle F, Churg A, Roggli V, Travis WD. The 2015 World Health Organization classification of tumors of the pleura: advances since the 2004 classification. J Thorac Oncol 2016; 11: 142-154.
Churg A, Sheffield BS, Galateau-Salle F. New markers for separating benign from malignant mesothelial proliferations: are we there yet? Arch Pathol Lab Med 2016; 140: 318- 321.
Walts AE, Hiroshima K, McGregor SM, Wu D, Husain AN, Marchevsky AM. BAP1 Immunostain and CDKN2A (p16) FISH analysis: clinical applicability for the diagnosis of malignant mesothelioma in effusions. Diagn Cytopathol 2016; 44: 599- 606.
Whitaker D. The cytology of malignant mesothelioma. Cytopathology 2000; 11: 139-151.
Pereira TC, Saad RS, Liu Y, Silverman JF. The diagnosis of malignancy in effusion cytology: a pattern recognition approach. Adv Anat Pathol 2006; 13: 174-184.
Su XY, Li GD, Liu WP, Xie B, Jiang YH. Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry. Diagn Cytopathol 2011; 39: 900-908.
Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, Borczuk AC, Butnor K, Cagle PT, Chirieac LR et al. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med 2013; 137: 647-667.
Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD, Thomas P. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 2011; 26: 125-132.
Bhatia A, Kumar Y. Cancer cell micronucleus: an update on clinical and diagnostic applications. APMIS 2014; 121: 569- 581.
Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D. DNA breaks and chromosome pulverization from errors in mitosis. Nature 2012; 482: 53-58.
Fischer AH, Zhao C, Li QK, Gustafson KS, Eltoum IE, Tambouret R, Benstein B, Savaloja LC, Kulesza P. Cytologic criteria of malignancy. J Cell Biochem 2010; 110: 795-811.
Luzhna L, Kathiria P, Kovalchuk O. Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond. Front Genet 2013; 4: 131.
Shi YH, Wang BW, Tuokan T, Li QZ, Zhang YJ. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance. Int J Clin Exp Pathol 2015; 8: 8426-8432.
Hemalatha A, Suresh TN, Harendara Kumar ML. Micronuclei in breast aspirates. Is scoring them helpful? J Cancer Res Ther 2014; 10: 309-311.
Kaur J, Dey P. Micronucleus to distinguish adenocarcinoma from reactive mesothelial cell in effusion fluid. Diagn Cytopathol 2009; 38: 177-179.
Samanta S, Dey P, Nijhawan R. The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast. Cytopathology 2010; 22: 111-114.
Goel S, Bhatia A, Dey P. Spontaneously occurring micronuclei in infiltrating ductal carcinoma of breast: a potential biomarker for aggressive phenotype detection? Diagn Cytopathol 2011; 41: 296-302.
Samanta S, Dey P, Nijhawan R. Micronucleus in cervical intraepithelial lesions and carcinoma. Acta Cytol 2010; 55: 42- 47.
Nilsson G. Micronuclei studied in fine needle goitre aspirates. Acta Pathol Microbiol Scand A 1978; 86: 201-204.
Kokenek-Unal TD, Coban I. Micronuclei and nuclear buds: highlighting overlooked indicators of chromosomal damage in thyroid aspiration smears. Diagn Cytopathol 2017; 45: 673- 680.