Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma.
<h4>Background</h4>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 mR...
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oai:doaj.org-article:584723351e014790ae5faad3194f11072021-12-02T20:22:00ZDetermination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma.1932-620310.1371/journal.pone.0010421https://doaj.org/article/584723351e014790ae5faad3194f11072010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20454689/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Jérôme VerineJacqueline Lehmann-CheHany SolimanJean-Paul FeugeasJean-Sébastien VidalPierre Mongiat-ArtusStéphanie BelhadjJosette PhilippeMatthieu LesageEvelyne WittmerStéphane ChanelAnne CouvelardSophie FerlicotNathalie Rioux-LeclercqJean-Michel VignaudAnne JaninStéphane GermainPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10421 (2010) |
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Medicine R Science Q Jérôme Verine Jacqueline Lehmann-Che Hany Soliman Jean-Paul Feugeas Jean-Sébastien Vidal Pierre Mongiat-Artus Stéphanie Belhadj Josette Philippe Matthieu Lesage Evelyne Wittmer Stéphane Chanel Anne Couvelard Sophie Ferlicot Nathalie Rioux-Leclercq Jean-Michel Vignaud Anne Janin Stéphane Germain Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| description |
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
| format |
article |
| author |
Jérôme Verine Jacqueline Lehmann-Che Hany Soliman Jean-Paul Feugeas Jean-Sébastien Vidal Pierre Mongiat-Artus Stéphanie Belhadj Josette Philippe Matthieu Lesage Evelyne Wittmer Stéphane Chanel Anne Couvelard Sophie Ferlicot Nathalie Rioux-Leclercq Jean-Michel Vignaud Anne Janin Stéphane Germain |
| author_facet |
Jérôme Verine Jacqueline Lehmann-Che Hany Soliman Jean-Paul Feugeas Jean-Sébastien Vidal Pierre Mongiat-Artus Stéphanie Belhadj Josette Philippe Matthieu Lesage Evelyne Wittmer Stéphane Chanel Anne Couvelard Sophie Ferlicot Nathalie Rioux-Leclercq Jean-Michel Vignaud Anne Janin Stéphane Germain |
| author_sort |
Jérôme Verine |
| title |
Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| title_short |
Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| title_full |
Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| title_fullStr |
Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| title_full_unstemmed |
Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| title_sort |
determination of angptl4 mrna as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/584723351e014790ae5faad3194f1107 |
| work_keys_str_mv |
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| _version_ |
1718374108118384640 |