Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review Clinical Cancer Research, 04/09/2012

Liao X et al. – Coexistence of PIK3CA (the PI3K p110? subunit) exon 9 and 20 mutations, but not PIK3CA mutation in either exon 9 or 20 alone, is associated with poor prognosis of colorectal cancer patients.

• We sequenced PIK3CA by pyrosequencing in 1,170 rectal and colon cancers in two prospective cohort studies, and found 189 (16%) PIK3CA mutated tumors.
• Mortality HR according to PIK3CA status was computed using Cox proportional hazards model, adjusting for clinical and molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and BRAF and KRAS mutations.

• Compared with PIK3CA wild-type cases, patients with concomitant PIK3CA mutations in exons 9 and 20 experienced significantly worse cancer-specific survival [log-rank P = 0.031; multivariate HR = 3.51; 95% confidence interval (CI): 1.28–9.62] and overall survival (log-rank P = 0.0008; multivariate HR = 2.68; 95% CI: 1.24–5.77).
• PIK3CA mutation in either exon 9 or 20 alone was not significantly associated with patient survival.
• No significant interaction of PIK3CA mutation with BRAF or KRAS mutation was observed in survival analysis.