title: PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer.
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.
authors: Unité Mixte de Recherche S1147, Paris Sorbonne Cité, Université Paris Descartes, INSERM, Paris, France; Assistance Publique-Hôpitaux de Paris, Service de Chirurgie Digestive et Hépato-Bilio-Pancréatique, Hôpital Pitié-Salpêtrière, Paris, France; Institut Universitaire de Cancérologie, Université Pierre et Marie Curie-Paris 6, Paris, France.
authors: Gilles
authors: G
authors: Manceau
authors: Laetitia
authors: L
authors: Marisa
authors: Valérie
authors: V
authors: Boige
authors: Alex
authors: A
authors: Duval
authors: Marie-Pierre
authors: MP
authors: Gaub
authors: Gérard
authors: G
authors: Milano
authors: Janick
authors: J
authors: Selves
authors: Sylviane
authors: S
authors: Olschwang
authors: Valérie
authors: V
authors: Jooste
authors: Michè
authors: M
authors: le Legrain
authors: Delphine
authors: D
authors: Lecorre
authors: Dominique
authors: D
authors: Guenot
authors: Marie-Christine
authors: MC
authors: Etienne-Grimaldi
authors: Sylvain
authors: S
authors: Kirzin
authors: Laurent
authors: L
authors: Martin
authors: Come
authors: C
authors: Lepage
authors: Anne-Marie
authors: AM
authors: Bouvier
authors: Pierre
authors: P
authors: Laurent-Puig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Biomarker; PIK3CA; colon cancer; microsatellite instability; mismatch repair; mutations; prognosis
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