Open AccessPIK3CA mutations predict recurrence in localized microsatellite stable colon cancer
Author(s) -
Manceau Gilles,
Marisa Laetitia,
Boige Valérie,
Duval Alex,
Gaub MariePierre,
Milano Gérard,
Selves Janick,
Olschwang Sylviane,
Jooste Valérie,
Legrain Michè,
Lecorre Delphine,
Guenot Dominique,
EtienneGrimaldi MarieChristine,
Kirzin Sylvain,
Martin Laurent,
Lepage Come,
Bouvier AnneMarie,
LaurentPuig Pierre
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.370
Subject(s) - microsatellite instability , medicine , confidence interval , colorectal cancer , oncology , univariate analysis , multivariate analysis , cohort , exon , mutation , point mutation , cancer , prospective cohort study , retrospective cohort study , gastroenterology , microsatellite , biology , genetics , gene , allele
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 .