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- Title
Determination of AngptI4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma.
- Authors
Verine, Jérôme; Lehmann-Che, Jacqueline; Soliman, Hany; Feugeas, Jean-Paul; Vidal, Jean-Sébastien; Mongiat-Artus, Pierre; Belhadj, Stéphanie; Philippe, Josette; Lesage, Matthieu; Wittmer, Evelyne; Chanel, Stéphane; Couvelard, Anne; Ferlicot, Sophie; Rioux-Leclercq, Nathalie; Vignaud, Jean-Michel; Janin, Anne; Germain, Stéphane
- Abstract
Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.
- Subjects
METASTASIS; RENAL cell carcinoma; HYPOXEMIA; RNA; ONCOLOGY; TUMOR growth
- Publication
PLoS ONE, 2010, Vol 5, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0010421