PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer

Cancer Medicine

Gilles Manceau⁵  Laetitia Marisa¹⁰  Valérie Boige⁵  Alex Duval¹  Marie-Pierre Gaub⁹  Gérard Milano⁴  Janick Selves³  Sylviane Olschwang⁶  Valérie Jooste⁸  Michè le Legrain⁹  Delphine Lecorre⁵  Dominique Guenot⁷  Marie-Christine Etienne-Grimaldi⁴  Sylvain Kirzin³  Laurent Martin^2,5  Come Lepage⁸  Anne-Marie Bouvier⁸ 

[1] Institut Universitaire de Cancérologie, Université Pierre et Marie Curie-Paris 6, Paris, France;Service d'anatomie et de cytologie pathologiques, CHU Dijon, France;Unité Mixte de Recherche 1037, Centre de Recherche en Cancérologie de Toulouse, Université de Toulouse III, INSERM, Toulouse, France;Laboratoire d'Oncopharmacologie EA 3836, Centre Antoine Lacassagne, Nice, France;Unité Mixte de Recherche S1147, Paris Sorbonne Cité, Université Paris Descartes, INSERM, Paris, France;Unité Mixte de Recherche S910, Faculté de Médecine La Timone, INSERM, Marseille, France;EA 3430 Progression tumorale et microenvironnement. Approches translationnelles et Epidémiologie. Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France;Registre Bourguignon des Cancers Digestifs, INSERM U866, CHU Dijon, France;Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France;“Cartes d'Identité des Tumeurs” Program, Ligue Nationale Contre le Cancer, Paris, France

关键词: Biomarker;    colon cancer;    microsatellite instability;    mismatch repair;    mutations;    PIK3CA;    prognosis;   

DOI  :  10.1002/cam4.370

来源: Wiley

【 摘 要 】

Abstract

PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently altered oncogenes in colon cancer (CC), but its prognostic value is still a matter of debate. Few reports have addressed the association between PIK3CA mutations and survival and their results are controversial. In the present study, we aimed to clarify the prognostic impact of PIK3CA mutations in stage I–III CC according to mismatch repair status. Fresh frozen tissue samples from two independent cohorts with a total of 826 patients who underwent curative surgical resection of CC were analyzed for microsatellite instability and screened for activating point mutations in exon 9 and 20 of PIK3CA by direct sequencing. Overall, 693 tumors (84%) exhibited microsatellite stability (MSS) and 113 samples (14%) harbored PIK3CA mutation. In the retrospective training cohort (n = 433), patients with PIK3CA-mutated MSS tumors (n = 47) experienced a significant increased 5-year relapse-free interval compared with PIK3CA wild-type MSS tumors (n = 319) in univariate analysis (94% vs. 68%, Log-rank P = 0. 0003) and in multivariate analysis (HR = 0.12; 95% confidence interval, 0.029–0.48; P = 0.0027). In the prospective validation cohort (n = 393), the favorable prognostic impact of PIK3CA mutations in MSS tumors (n = 327) was confirmed (83% vs. 67%, Log-rank P = 0.04). Our study showed that PIK3CA mutations are associated with a good prognosis in patients with MSS stage I–III CC.

【 授权许可】

CC BY   
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.