Journal Article

Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma

Soliman, Hany, Janin, Anne, Vidal, Jean-Sébastien, Rioux-Leclercq, Nathalie, Feugeas, Jean-Paul, Chanel, Stéphane, Ferlicot, Sophie, Wittmer, Evelyne, Philippe, Josette, Vignaud, Jean-Michel, Germain, Stéphane, Lehmann-Che, Jacqueline, Belhadj, Stéphanie, Mongiat-Artus, Pierre, Couvelard, Anne, Verine, Jérôme, Lesage, Matthieu

2010

Overview

We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors. Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status. Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10(-49), Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiopoietin / Angiopoietin-like 4 Protein / Angiopoietins - genetics / Biomarkers / Cancer / Cancer metastasis / Carcinoma / Carcinoma, Renal Cell - diagnosis / Carcinoma, Renal Cell - pathology / Carcinoma, Renal Cell - secondary / Cell growth / Chi-square test / Classification / Clear cell-type renal cell carcinoma / Deactivation / Diagnosis, Differential / Diagnostic systems / Gene expression / Human health and pathology / Humans / Hypoxia / In Situ Hybridization / Inactivation / Kidney cancer / Life Sciences / Medical diagnosis / Medical prognosis / Messenger RNA / Metastases / Metastasis / Molecular Diagnostic Techniques / Mutation / Neoplasm Metastasis / Nephrology / Neuroendocrine tumors / Organs / Pancreas / Pancreatic cancer / Pathology/Histopathology / Patients / Proteins / Retrospective Studies / RNA, Messenger - analysis / RNA, Neoplasm - analysis / Survival / Tumors / Urology and Nephrology / Urology/Renal Cancer / Vascular endothelial growth factor / VHL protein