Objective: The aim of our study was to determine the diagnostic value of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells (MAC) and reactive mesothelial cells (RMC) in effusion fluids. Study Design: A total of 237 cell block specimens from pleural and peritoneal effusions, including 196 malignant effusions with MAC and 41 benign effusions with RMC, were stained with antibodies against MUC1 and MUC4. Membranous staining with or without cytoplasmic staining was considered to be positive. Results: MUC1 immunoreactivity was observed in 194 (99.0%) of 196 cases of MAC and in 20 (48.8%) of 41 cases of RMC. MUC4 immunoreactivity was observed in 174 (88.8%) of 196 cases of MAC and in 4 (9.8%) of 41 cases of RMC. For distinguishing MAC from RMC, the MUC1 reactivity was found to be 99.0% sensitive and 51.2% specific with a positive predictive value of 90.7% and a negative predictive value of 91.3%. The sensitivity of MUC4 for MAC was 88.8%, the specificity was 90.2%, the negative predictive value was 62.7%, and the positive predictive value was 97.8%. Conclusion: Our data suggest that MUC4 appears to be a sensitive and specific marker for differentiating between MAC and RMC.

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.
Koss LG: Koss' Diagnostic Cytology and Its Histopathological Bases, ed 5. Philadelphia, Lippincott Williams & Wilkins, 2006, pp 919-948.
Mohanty SK, Dey P: Serous effusions: Diagnosis of malignancy beyond cytomorphology: an analytic review. Postgrad Med J 2003;79:569-574.
Fetsch PA, Abati A: Immunocytochemistry in effusion cytology: a contemporary review. Cancer 2001;93:293-308.
Fetsch PA, Simsir A, Brosky K, Abati A: Comparison of three commonly used cytologic preparations in effusion immunocytochemistry. Diagn Cytopathol 2002;26:61-66.
Saleh HA, El-Fakharany M, Makki H, Kadhim A, Masood S: Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: the utility of immunocytochemical panel in the differential diagnosis. Diagn Cytopathol 2009;37:324-332.
Ikeda K, Tate G, Suzuki T, Kitamura T, Mitsuya T: Diagnostic usefulness of EMA, IMP3, and GLUT-1 for the immunocytochemical distinction of malignant cells from reactive mesothelial cells in effusion cytology using cytospin preparations. Diagn Cytopathol 2011;39:395-401.
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.
Hollingsworth MA, Swanson BJ: Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 2004;4:45-60.
Mall AS: Analysis of mucins: role in laboratory diagnosis. J Clin Pathol 2008;61:1018-1024.
Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, Goto M: Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 2011;61:697-716.
Jonckheere N, Van Seuningen I: The membrane-bound mucins: from cell signalling to transcriptional regulation and expression in epithelial cancers. Biochimie 2010;92:1-11.
Yu CJ, Shew JY, Liaw YS, Kuo SH, Luh KT, Yang PC: Application of mucin quantitative competitive reverse transcription polymerase chain reaction in assisting the diagnosis of malignant pleural effusion. Am J Respir Crit Care Med 2001;164:1312-1318.
Llinares K, Escande F, Aubert S, Buisine MP, de Bolos C, Batra SK, Gosselin B, Aubert JP, Porchet N, Copin MC: Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma. Mod Pathol 2004;17:150-157.
Passebosc-Faure K, Li G, Lambert C, Cottier M, Gentil-Perret A, Fournel P, Pérol M, Genin C: Evaluation of a panel of molecular markers for the diagnosis of malignant serous effusions. Clin Cancer Res 2005;11:6862-6867.
Davidson B, Baekelandt M, Shih IeM: MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells. Diagn Cytopathol 2007;35:756-760.
Creaney J, Segal A, Sterrett G, Platten MA, Baker E, Murch AR, Nowak AK, Robinson BW, Millward MJ: Overexpression and altered glycosylation of MUC1 in malignant mesothelioma. Br J Cancer 2008;98:1562-1569.
Han L, Pansare V, Al-Abbadi M, Husain M, Feng J: Combination of MUC5ac and WT-1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology. Diagn Cytopathol 2010;38:333-336.
Kim JH, Kim GE, Choi YD, Lee JS, Lee JH, Nam JH, Choi C: Immunocytochemical panel for distinguishing between adenocarcinomas and reactive mesothelial cells in effusion cell blocks. Diagn Cytopathol 2009;37:258-261.
Kim JH, Kim YS, Choi YD, Lee JS, Park CS: Utility of napsin A and thyroid transcription factor 1 in differentiating metastatic pulmonary from non-pulmonary adenocarcinoma in pleural effusion. Acta Cytol 2011;55:266-270.
Rakha EA, Boyce RW, Abd El-Rehim D, Kurien T, Green AR, Paish EC, Robertson JF, Ellis IO: Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 2005;18:1295-1304.
Workman HC, Miller JK, Ingalla EQ, Kaur RP, Yamamoto DI, Beckett LA, Young LJ, Cardiff RD, Borowsky AD, Carraway KL, Sweeney C, Carraway KL 3rd: The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells. Breast Cancer Res 2009;11:R70.
Lau SK, Weiss LM, Chu PG: Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol 2004;122:61-69.
Park SY, Kim BH, Kim JH, Lee S, Kang GH: Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med 2007;131:1561-1567.
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