PIK3CA Mutation is Strongly Associated with K-ras 12/13 Mutation in Stage II/III Colorectal Cancer


Session type:

Katie Southward1, Morag Taylor1, Phil Chambers1, Kelly Handley2, Laura Magill2, Claire Beaumont1, Susan Richman1, Matt Seymour3, David Kerr4, Richard Gray4, Phil Quirke1
1Leeds Institute of Molecular Medicine, Leeds, UK, 2Birmingham Clinical Trials Unit, Birmingham, UK, 3CRUK Cancer Centre, Leeds, UK, 4University of Oxford, Oxford, UK


Ras and Raf mutations in colorectal cancer are associated with poorer outcome and lack of response to anti-EGFR antibodies. The importance of PIK3CA mutations has not been as extensively investigated. In this study the relationship between PIK3CA, mutations in K-ras, N-ras, B-raf and a number of other clinicopathological features have been examined in Quasar-I, a large phase III adjuvant chemotherapy clinical trial.


PIK3CA mutation status was investigated in a test set of 900 cases. Tumour DNA was extracted from a formalin-fixed paraffin-embedded block in each case. We have assessed PIK3CA mutations in exon 9 (codons 542/545/546) and exon 20 (codon 1047) by pyrosequencing.


Summary of results: Data was available in 873 cases. The mutation rate was 13.9 %. 83 cases had a mutation in exon 9 and 38 cases had a mutation in exon 20. There were no double PIK3CA mutations. 76 (62.8% of all PIK3CA mutated cases) had a K-ras12/13 and a PIK3CA mutation (P ≤ 0.0001). There was no association between PIK3CA mutation and sex, site, stage, tumour content, stromal content, K-ras 61, K-ras 146, N-ras 12/13, N-ras 61 or B-raf V600E mutations.


PIK3CA mutations are associated with K-ras mutations and this should be considered when ascribing a poor outcome to PIK3CA mutations.