Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma.

BACKGROUND Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet. METHODS We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma. FINDINGS Mean serum SMRP level was higher in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L; benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793. INTERPRETATION We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.

[1]  M. Grégoire,et al.  Cytotoxic T cell responses against mesothelioma by apoptotic cell-pulsed dendritic cells. , 2004, American journal of respiratory and critical care medicine.

[2]  R. Odze,et al.  Immunohistochemistry Can Help Distinguish Metastatic Pancreatic Adenocarcinomas From Bile Duct Adenomas and Hamartomas of the Liver , 2005, The American journal of surgical pathology.

[3]  B. Robinson,et al.  Localised spontaneous regression in mesothelioma -- possible immunological mechanism. , 2001, Lung cancer.

[4]  R L Iman,et al.  Analysis of covariance using the rank transformation. , 1982, Biometrics.

[5]  N. Ordóñez The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study. , 2004, Human pathology.

[6]  A. Chambers,et al.  Role of osteopontin in tumour progression , 2004, British Journal of Cancer.

[7]  N Urban,et al.  Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma. , 2004, Gynecologic oncology.

[8]  S. Burdach,et al.  Forced expression of deltaN-TCF-1B in colon cancer derived cell lines is accompanied by the induction of CEACAM5/6 and mesothelin. , 2005, Cancer letters.

[9]  G. Hillerdal,et al.  Hyaluronan in pleural effusions and in serum , 1991, Cancer.

[10]  A. Musk,et al.  Mesothelin-family proteins and diagnosis of mesothelioma , 2003, The Lancet.

[11]  H. Pass,et al.  Malignant pleural mesothelioma. , 2004, Current problems in cancer.

[12]  I. Pastan,et al.  Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[14]  H. Weill,et al.  Diagnosis and initial management of nonmalignant diseases related to asbestos. , 2005, American journal of respiratory and critical care medicine.

[15]  F. Ece,et al.  Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. , 2001, American journal of respiratory cell and molecular biology.

[16]  Bart N Lambrecht,et al.  Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. , 2005, American journal of respiratory and critical care medicine.

[17]  E. Lander,et al.  Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  N. Umesaki,et al.  Binding of Ovarian Cancer Antigen CA125/MUC16 to Mesothelin Mediates Cell Adhesion* , 2004, Journal of Biological Chemistry.

[19]  N. Ordóñez The Immunohistochemical Diagnosis of Mesothelioma: A Comparative Study of Epithelioid Mesothelioma and Lung Adenocarcinoma , 2003, The American journal of surgical pathology.

[20]  M. Cullen Serum osteopontin levels--is it time to screen asbestos-exposed workers for pleural mesothelioma? , 2005, The New England journal of medicine.

[21]  James M. Wilson,et al.  Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy , 2005, Clinical Cancer Research.

[22]  Ira Pastan,et al.  Mesothelin: a new target for immunotherapy. , 2004, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  I. Pastan,et al.  Monoclonal Antibody K1 Reacts With Epithelial Mesothelioma but not With Lung Adenocarcinoma , 1992, The American journal of surgical pathology.

[24]  C. Moskaluk,et al.  Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas. , 2003, Human pathology.

[25]  N. Ordóñez Value of Mesothelin Immunostaining in the Diagnosis of Mesothelioma , 2003, Modern Pathology.

[26]  K. Ohtsubo,et al.  Expression of Mesothelin mRNA in Pure Pancreatic Juice From Patients With Pancreatic Carcinoma, Intraductal Papillary Mucinous Neoplasm of the Pancreas, and Chronic Pancreatitis , 2005, Pancreas.

[27]  M. van de Rijn,et al.  Distinction between serous tumors of low malignant potential and serous carcinomas based on global mRNA expression profiling. , 2005, Gynecologic oncology.

[28]  J. Mellon,et al.  Improving the utility of prostate specific antigen (PSA) in the diagnosis of prostate cancer: the use of PSA derivatives and novel markers , 2002, Postgraduate medical journal.

[29]  N. Ordóñez,et al.  Application of Mesothelin Immunostaining in Tumor Diagnosis , 2003, The American journal of surgical pathology.

[30]  Z. Ye,et al.  Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Drapkin,et al.  Expression of candidate tumor markers in ovarian carcinoma and benign ovary: evidence for a link between epithelial phenotype and neoplasia. , 2004, Human pathology.

[32]  N. Sardesai,et al.  Soluble mesothelin related peptides: A potential biomarker for malignant pleural mesothelioma , 2005 .