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

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 us...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861680/
https://www.ncbi.nlm.nih.gov/pubmed/20454689
http://dx.doi.org/10.1371/journal.pone.0010421
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author 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
author_facet 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
author_sort Verine, Jérôme
collection PubMed
description 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.
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spelling pubmed-28616802010-05-07 Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma 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 PLoS One Research Article 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. Public Library of Science 2010-04-29 /pmc/articles/PMC2861680/ /pubmed/20454689 http://dx.doi.org/10.1371/journal.pone.0010421 Text en Verine et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861680/
https://www.ncbi.nlm.nih.gov/pubmed/20454689
http://dx.doi.org/10.1371/journal.pone.0010421
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