Abstract
Purpose
Malignant pleural effusion is an important staging criterion in non-small cell lung cancer (NSCLC). Although cytologic examination remains the major diagnostic tool for NSCLC-related malignant pleural effusion, sometimes other invasive methods maybe required. Aberrant activation of Wnt signaling pathway due to Wnt inhibitory factor-1 (WIF-1) promoter region hypermethylation is common in NSCLC, and can be specifically detected by methylation-specific polymerase chain reaction (MSP). We hypothesized that WIF-1 promoter region MSP can be used to improve the diagnostic yield of NSCLC-related malignant pleural effusion.
Methods
We performed WIF-1 promoter region MSP in 36 definite malignant pleural effusions from consecutive NSCLC patients and 35 pleural effusion specimens of benign origin. Pleural effusion cells were collected for DNA extraction. After bisulfite treatment, DNA was amplified by methylation-specific and unmethylation-specific primers, respectively, to identify the methylation status of WIF-1 promoter region.
Results
The results of WIF-1 promoter region MSP were positive in 25 (69.4%) of 36 NSCLC patients with malignant pleural effusion. In addition, the results of WIF-1 promoter region MSP were negative in all 35 patients with pleural effusion of benign origin. The age, gender, and smoking status of patients were not correlated with the methylation status of WIF-1 promoter region in NSCLC-related malignant pleural effusion.
Conclusions
WIF-1 promoter region MSP might be used as an adjuvant tool to complement cytologic examination for the diagnosis of NSCLC-related malignant pleural effusion.
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References
Brock MV, Hooker CM, Yung R, Guo M, Han Y, Ames SE et al (2005) Can we improve the cytologic examination of malignant pleural effusions using molecular analysis? Ann Thorac Surg 80:1241–1247. doi:10.1016/j.athoracsur.2005.05.088
Dikmen G, Dikmen E, Kara M, Sahin E, Dogan P, Ozdemir N (2003) Diagnostic implications of telomerase activity in pleural effusions. Eur Respir J 22:422–426. doi:10.1183/09031936.03.00001303
Huang MJ, Lim KH, Tzen CY, Hsu HS, Yen Y, Huang BS (2005) EGFR mutations in malignant pleural effusion of non-small cell lung cancer: a case report. Lung Cancer 49:413–415. doi:10.1016/j.lungcan.2005.02.016
Katayama H, Hiraki A, Aoe K, Fujiwara K, Matsuo K, Maeda T et al (2007) Aberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusion. Int J Cancer 120:2191–2195. doi:10.1002/ijc.22576
Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634. doi:10.1242/jcs.00623
Kim YT, Lee SH, Sung SW, Kim JH (2005) Can aberrant promoter hypermethylation of CpG islands predict the clinical outcome of non-small cell lung cancer after curative resection? Ann Thorac Surg 79:1180–1188. doi:10.1016/j.athoracsur.2004.09.060
Liang QL, Shi HZ, Qin XJ, Liang XD, Jiang J, Yang HB (2008) Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta-analysis. Thorax 63:35–41. doi:10.1136/thx.2007.077958
Licchesi JD, Westra WH, Hooker CM, Machida EO, Baylin SB, Herman JG (2008) Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung. Carcinogenesis 29:895–904. doi:10.1093/carcin/bgn017
Lin YC, You L, Xu Z, He B, Mikami I, Thung E et al (2006) Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines. Biochem Biophys Res Commun 341:635–640. doi:10.1016/j.bbrc.2005.12.220
Lu D, Zhao Y, Tawatao R, Cottam HB, Sen M, Leoni LM et al (2004) Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 101:3118–3123. doi:10.1073/pnas.0308648100
Lustig B, Behrens J (2003) The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 129:199–221
Marsit CJ, McClean MD, Furniss CS, Kelsey KT (2006) Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma. Int J Cancer 119:1761–1766. doi:10.1002/ijc.22051
Maskell NA, Butland RJ (2003) BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 58(Suppl 2):ii8–ii17
Mazieres J, He B, You L, Xu Z, Jablons DM (2005) Wnt signaling in lung cancer. Cancer Lett 222:1–10. doi:10.1016/j.canlet.2004.08.040
Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I et al (2004) Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res 64:4717–4720. doi:10.1158/0008-5472.CAN-04-1389
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790. doi:10.1126/science.275.5307.1787
Neragi-Miandoab S (2006) Malignant pleural effusion, current and evolving approaches for its diagnosis and management. Lung Cancer 54:1–9. doi:10.1016/j.lungcan.2006.04.016
Rhee CS, Sen M, Lu D et al (2002) Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene 21:6598–6605. doi:10.1038/sj.onc.1205920
Shitrit D, Zingerman B, Shitrit AB, Shlomi D, Kramer MR (2005) Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature. Oncologist 10:501–507. doi:10.1634/theoncologist.10-7-501
Sugiura S, Ando Y, Minami H, Ando M, Sakai S, Shimokata K (1997) Prognostic value of pleural effusion in patients with non-small cell lung cancer. Clin Cancer Res 3:47–50
Suzuki M, Shigematsu H, Nakajima T, Kubo R, Motohashi S, Sekine Y et al (2007) Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer. Clin Cancer Res 13:6087–6092. doi:10.1158/1078-0432.CCR-07-0591
Weeraratna AT, Jiang Y, Hostetter G et al (2002) Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1:279–288. doi:10.1016/S1535-6108(02)00045-4
Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M et al (2003) WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. J Pathol 201:204–212. doi:10.1002/path.1449
Woenckhaus M, Grepmeier U, Werner B, Schulz C, Rockmann F, Wild PJ et al (2005) Microsatellite analysis of pleural supernatants could increase sensitivity of pleural fluid cytology. J Mol Diagn 7:517–524
Acknowledgments
The authors thank Dr. V. Courtney Broaddus for helping design the experiment. This study was supported by the grant No. 95-2320-B-182-057 from National Science Council, Taiwan, R.O.C. to C.-T. Yang.
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T.-M. Yang and S.-W. Leu are the first authors and contributed equally.
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Yang, TM., Leu, SW., Li, JM. et al. WIF-1 promoter region hypermethylation as an adjuvant diagnostic marker for non-small cell lung cancer-related malignant pleural effusions. J Cancer Res Clin Oncol 135, 919–924 (2009). https://doi.org/10.1007/s00432-008-0527-7
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DOI: https://doi.org/10.1007/s00432-008-0527-7