Concomitant Presence of PIK3CA Mutations in Both Exons 9 and 20 Predicts Aggressive Behavior of Colorectal Cancer
Shuji Ogino, Xiaoyun Liao, Teppei Morikawa, Charles Fuchs. Brigham and Women's Hospital, Boston; Dana-Farber Cancer Institute, Boston
Background: PIK3CA mutation plays an important role in colorectal carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20 mutations trigger different biological effects, and that concomitant mutations in both exons 9 and 20 lead to enhanced tumor promoting effects. Thus, we hypothesized that PIK3CA exon 9 mutation and exon 20 mutation might have differential effects on colorectal cancer behavior, and that concomitant PIK3CA mutations in both exons 9 and 20 might confer aggressive tumor behavior.
Design: We sequenced PIK3CA by pyrosequencing on 1170 colorectal cancers. Cox proportional hazards model was performed to compute mortality hazard ratio (HR) by PIK3CA status, adjusting for clinical, stage and tumor variables including microsatellite instability, and KRAS and BRAF mutation status.
Results: PIK3CA mutation was detected in 189 (16% of 1170) cases; 109 in only exon 9, 73 in only exon 20 and 7 in both exons 9 and 20. Compared to PIK3CA wild-type cases, patients with concomitant PIK3CA mutations in both exons 9 and 20 experienced significantly higher colorectal cancer-specific mortality [univariate HR = 2.84; 95% confidence interval (CI), 1.05-7.69; multivariate HR = 3.51; 95% CI, 1.28-9.62), and higher overall mortality (univariate HR = 3.37; 95% CI, 1.58-7.15; multivariate HR = 2.68; 95% CI, 1.24-5.77).
In contrast, the presence of PIK3CA mutation in only either exon 9 or 20 was not significantly associated with patient survival.
Conclusions: The presence of concomitant PIK3CA mutations in both exons 9 and 20 in colorectal cancer is associated with poor prognosis. Our data support a more potent oncogenic effect of PIK3CA double mutants in both exons 9 and 20.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 71, Tuesday Afternoon