- Volume 15 Issue 1
Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.
Diagnosis;discrimination;malignant pleural effusion;tumor markers;unknown primary tumor
- Destombe C, Botton E, Le Gal G, et al (2007). Investigations for bone metastasis from an unknown primary. Joint Bone Spine, 74, 85-9. https://doi.org/10.1016/j.jbspin.2006.05.009
- Kwee TC, Takahara T, Ochiai R, et al (2008). Diffusionweighted whole-body imaging with background body signal suppression (DWIBS): features and potential applications in oncology. Eur Radiol, 18, 1937-52. https://doi.org/10.1007/s00330-008-0968-z
- Kwee T C, Kwee RM (2009). Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol, 19, 731-44. https://doi.org/10.1007/s00330-008-1194-4
- Liang QL, Shi HZ, Qin XJ, et al (2008). Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta analysis. Thorax, 63, 35-41. https://doi.org/10.1136/thx.2007.077958
- Cheng M, Chen Y, Yu X, et al (2008). Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer. BMC Cancer, 8, 156. https://doi.org/10.1186/1471-2407-8-156
- Davidson B, Baekelandt M, Shih IeM (2007). MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells. Diagn Cytopathol, 35, 756-60. https://doi.org/10.1002/dc.20771
- Elstrand MB, Kleinberg L, Kohn EC, et al (2009). Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. Int J Gynecol Pathol, 28, 211-21. https://doi.org/10.1097/PGP.0b013e31818b0f5e
- Gaspar MJ, De Miguel J, Garcia Diaz JD, et al (2008). Clinical utility of a combination of tumour markers in the diagnosis of malignant pleural effusions. Anticancer Res, 28, 2947-52.
- Heffner JE, Nietert PJ, Barbieri C (2000). Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions. Chest, 117, 79-86. https://doi.org/10.1378/chest.117.1.79
- Abbruzzese JL, Abbruzzese MC, Hess KR, et al (1994). Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol, 12, 1272-80.
- Bocking A, Pomjansky N, Buckstegge B, et al (2009). Immunocytochemical identification of carcinomas of unknown primaries on fine-needle-aspiration-biopsies. Pathologe, 30, 158-60. https://doi.org/10.1007/s00292-009-1184-6
- Jiang B, Wu GP, Zhao YJ, et al (2008). Transcription expression and clinical significance of TTF-1 mRNA in pleural effusion of patients with lung cancer. Diagn Cytopathol, 36, 849-54. https://doi.org/10.1002/dc.20926
- van de Molengraft FJ, Vooijs GP (1989). Survival of patients with malignancy-associated effusions. Acta Cytol, 33, 911-6.
- Shitrit D, Zingerman B, Shitrit AB, et al (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, 501-7. https://doi.org/10.1634/theoncologist.10-7-501
- SUN Yongchang, HU Hong, XIA Guoguang, XU Wenbing, WANG Hongwu (2011). An invesigation on diagnosis of pleural effusions in some teaching hospitals at Beijing district. Chin J Tube Resp Dise, 34, 233-.
- Tsukushi S, Katagiri H, Kataoka T, et al (2006). Serum tumor markers in skeletal metastasis. Jpn J Clin Oncol, 36, 439-44. https://doi.org/10.1093/jjco/hyl046
- Watanabe N (1996). Organ specificity of tumor markers and its application for clinical diagnosis. Nihon Rinsho, 54, 1592-6.
- Zhu W, Michael CW (2007). WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions. Diagn Cytopathol, 35, 370-5. https://doi.org/10.1002/dc.20643
- Bonnefoi H, Smith IE (1996). How should cancer presenting as a malignant pleural effusion be managed? Br J Cancer, 74, 832-5. https://doi.org/10.1038/bjc.1996.444
- Botte G, Laferrere L, Etchepare S, et al (1990). Diagnostic value of tumor markers in pleural effusions. Medicina, 50, 213-6.
- Cascinu S, Del Ferro E, Barbanti I, et al (1997). Tumor markers in the diagnosis of malignant serous effusions. Am J Clin Oncol, 20, 247-50. https://doi.org/10.1097/00000421-199706000-00007
- Cellerin L, Marcq M, Sagan C, et al (2008). Malignant pleural effusion as the presenting site of cancer: comparison with metastatic pleural effusions from known cancers. Rev Mal Respir, 25, 1104-9. https://doi.org/10.1016/S0761-8425(08)74980-5
- Pavlidis N, Kalef-Ezra J, Briassoulis E, et al (1994). Evaluation of six tumor markers in patients with carcinoma of unknown primary. Med Pediatr Oncol, 22, 162-7. https://doi.org/10.1002/mpo.2950220303
- Losa Gaspa F, Germa JR, Albareda JM, et al (2002). Metastatic cancer presentation. Validation of a diagnostic algorithm with 221 consecutive patients. Rev Clin Esp, 202, 313-9. https://doi.org/10.1016/S0014-2565(02)71065-5
- Malati T (2007). Tumour markers: An overview. Indian J Clin Biochem, 22, 17-31. https://doi.org/10.1007/BF02913308
- Panza N, Lombardi G, De Rosa M, et al (1987). High serum thyroglobulin levels. Diagnostic indicators in patients with metastases from unknown primary sites. Cancer, 60, 2233-6. https://doi.org/10.1002/1097-0142(19871101)60:9<2233::AID-CNCR2820600922>3.0.CO;2-Y
- Pavlidis N, Briasoulis E, Pentheroudakis G (2010). Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 21, v228-31. https://doi.org/10.1093/annonc/mdq193
- Pomjanski N, Grote HJ, Doganay P, et al (2005). Immunocytochemical identification of carcinomas of unknown primary in serous effusions. Diagn Cytopathol, 33, 309-15. https://doi.org/10.1002/dc.20393
- Porcel JM, Vives M, Esquerda A, et al (2004). 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, 126, 1757-63. https://doi.org/10.1378/chest.126.6.1757
- Pu RT, Giordano TJ, Michael CW (2008). Utility of cytology microarray constructed from effusion cell blocks for immunomarker validation. Cancer, 114, 300-6. https://doi.org/10.1002/cncr.23797
- Roberts ME, Neville E, Berrisford RG, et al (2010). Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax, 65, ii32-40.
- Sears D, Hajdu SI (1987). The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol, 31, 85-97.
- Liu L, Cohen C, Siddiqui M T (2012). Thyroid transcription factor 1 and napsin a double staining in lung adenocarcinoma in pleural fluid. Acta Cytol, 56, 425-30. https://doi.org/10.1159/000337439
- Utility of Nuclear Morphometry in Effusion Cytology vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6919
- Tumor Markers in Serum and Ascites in the Diagnosis of Benign and Malignant Ascites vol.16, pp.2, 2015, https://doi.org/10.7314/APJCP.2015.16.2.719
- Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer vol.107, pp.9, 2016, https://doi.org/10.1111/cas.12987
- Pleural fluid carcinoembryonic antigen as a biomarker for the discrimination of tumor-related pleural effusion vol.11, pp.6, 2016, https://doi.org/10.1111/crj.12431
- Diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo cells and carcinoembryonic antigen in differentiating malignant from benign pleural effusion vol.37, pp.3, 2016, https://doi.org/10.1007/s13277-015-4174-8
- Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis vol.22, pp.2, 2017, https://doi.org/10.1007/s10147-016-1073-y
Supported by : Health Department of Shandong Province, Science and Technology Department of Jinan