Aziz Zaanan1,2, Claire Calmel3, Julie Henriques4,5, Magali Svrcek3,6, Hélène Blons7, Christèle Desbois-Mouthon3, Fatiha Merabtene3,8, Claire Goumard3, Yann Parc3,9, Brice Gayet10, Julien Taieb11, Pierre Validire12, Christophe Louvet13, Jean-François Fléjou3,6, Yves Le Bouc3, Françoise Praz14,15. 1. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, UMR_S938, F-75012, Paris, France. aziz.zaanan@aphp.fr. 2. Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, APHP, Paris Descartes University, Paris, France. aziz.zaanan@aphp.fr. 3. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, UMR_S938, F-75012, Paris, France. 4. Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, Besançon University Hospital, Besançon, France. 5. University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France. 6. Department of Pathology, Saint-Antoine Hospital, AP-HP, Paris, France. 7. Department of Biology, European Georges Pompidou Hospital, APHP, Paris Descartes University, Paris, France. 8. Histomorphology Platform, UMS 30 Lumic, F-75012, Paris, France. 9. Department of Digestive Surgery, Saint-Antoine Hospital, AP-HP, Paris, France. 10. Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France. 11. Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, APHP, Paris Descartes University, Paris, France. 12. Department of Pathology, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France. 13. Department of Oncology, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France. 14. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, UMR_S938, F-75012, Paris, France. francoise.praz@upmc.fr. 15. Centre National de la Recherche Scientifique (CNRS), Paris, France. francoise.praz@upmc.fr.
Abstract
PURPOSE: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC). METHODS: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Associations of markers with DFS were analysed using Cox proportional hazards models. RESULTS: Hundred and fifty-one CC patients were included (median age, 66.6 years; female, 54.3%). Low levels of IGF1R and IGF-II protein expression were observed in 16.1% and 10.7% of the cases, respectively. No significant differences in clinicopathological characteristics between patients with tumours expressing low IGF1R or IGF-II protein levels and those with high levels were observed. A low IGF1R protein expression was found to be significantly associated with a shorter DFS (HR 3.32; 95% CI, 1.7-6.31; p = 0.0003), while no association was observed between IGF-II protein expression and DFS (HR 0.91; 95% CI, 0.28-2.96; p = 0.87). In a multivariate analysis, IGF1R protein status remained an independent prognostic factor for DFS (HR 2.73; 95% CI, 1.40-5.31; p = 0.003). Furthermore, we found that neither IGF1R nor IGF2 mRNA expression levels as measured by qRT-PCR correlated with the respective protein expression levels as assessed by immunohistochemistry. Neither of the mRNA expression levels was significantly associated with DFS. CONCLUSIONS: From our data we conclude that low IGF1R protein expression represents a poor prognostic biomarker in stage III colon cancer.
PURPOSE: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC). METHODS: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Associations of markers with DFS were analysed using Cox proportional hazards models. RESULTS: Hundred and fifty-one CCpatients were included (median age, 66.6 years; female, 54.3%). Low levels of IGF1R and IGF-II protein expression were observed in 16.1% and 10.7% of the cases, respectively. No significant differences in clinicopathological characteristics between patients with tumours expressing low IGF1R or IGF-II protein levels and those with high levels were observed. A low IGF1R protein expression was found to be significantly associated with a shorter DFS (HR 3.32; 95% CI, 1.7-6.31; p = 0.0003), while no association was observed between IGF-II protein expression and DFS (HR 0.91; 95% CI, 0.28-2.96; p = 0.87). In a multivariate analysis, IGF1R protein status remained an independent prognostic factor for DFS (HR 2.73; 95% CI, 1.40-5.31; p = 0.003). Furthermore, we found that neither IGF1R nor IGF2 mRNA expression levels as measured by qRT-PCR correlated with the respective protein expression levels as assessed by immunohistochemistry. Neither of the mRNA expression levels was significantly associated with DFS. CONCLUSIONS: From our data we conclude that low IGF1R protein expression represents a poor prognostic biomarker in stage III colon cancer.
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