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PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer

2015; Wiley; Volume: 4; Issue: 3 Linguagem: Inglês

10.1002/cam4.370

2045-7634

Gilles Manceau, Laëtitia Marisa, Valérie Boige, Alex Duval, Marie‐Pierre Gaub, G. Milano, Janick Sèlves, Sylviane Olschwang, Valérie Jooste, Michè le Legrain, Delphine Lecorre, Dominique Guénot, Marie‐Christine Etienne‐Grimaldi, Sylvain Kirzin, Laurent Martin, Côme Lepage, Anne‐Marie Bouvier, Pierre Laurent‐Puig,

Gastric Cancer Management and Outcomes

Abstract PIK 3 CA , which encodes the p110 α catalytic subunit of PI 3K α , 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 PIK 3 CA mutations and survival and their results are controversial. In the present study, we aimed to clarify the prognostic impact of PIK 3 CA 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 PIK 3 CA by direct sequencing. Overall, 693 tumors (84%) exhibited microsatellite stability ( MSS ) and 113 samples (14%) harbored PIK 3 CA mutation. In the retrospective training cohort ( n = 433), patients with PIK 3 CA ‐mutated MSS tumors ( n = 47) experienced a significant increased 5‐year relapse‐free interval compared with PIK 3 CA 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 PIK 3 CA mutations in MSS tumors ( n = 327) was confirmed (83% vs. 67%, Log‐rank P = 0.04). Our study showed that PIK 3 CA mutations are associated with a good prognosis in patients with MSS stage I–III CC .