Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma.
| Autor: | Verine J; INSERM, U833, Paris, France., Lehmann-Che J, Soliman H, Feugeas JP, Vidal JS, Mongiat-Artus P, Belhadj S, Philippe J, Lesage M, Wittmer E, Chanel S, Couvelard A, Ferlicot S, Rioux-Leclercq N, Vignaud JM, Janin A, Germain S |
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| Jazyk: | angličtina |
| Zdroj: | PloS one [PLoS One] 2010 Apr 29; Vol. 5 (4), pp. e10421. Date of Electronic Publication: 2010 Apr 29. |
| DOI: | 10.1371/journal.pone.0010421 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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