PIK3CA Activating Mutation in Colorectal Carcinoma: A Stratified Analysis in a Prospective Cohort
Christophe Rosty, Joanne P Young, Michael D Walsh, Mark Clendenning, Mark A Jenkins, Aung Ko Win, Melissa C Southey, Susan Parry, John L Hopper, Graham G Giles, Elizabeth Williamson, Dallas R English, Daniel D Buchanan. Queensland Institute of Medical Research, Brisbane, Australia; University of Queensland, Brisbane, Australia; Envoi Pathology, Brisbane, Australia; Sullivan Nicolaides Pathology, Brisbane, Australia; University of Melbourne, Melbourne, Australia; Middlemore Hospital, Auckland, New Zealand; Cancer Council Victoria, Melbourne, Australia
Background: Colorectal carcinomas (CRC) with somatic PIK3CA mutations comprise 10-15% of all CRCs. The aim of this study was to examine the characteristics of PIK3CA-mutated CRC in a large well-characterized prospective population-based cohort to determine how these mutations relate to pathology phenotype, clinical outcome, and to other molecular alterations.
Design: PIK3CA mutation testing was carried out on 780 incident CRCs from the Melbourne Collaborative Cohort Study (mean age at diagnosis: 68 years). MGMT status was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability phenotype, KRAS and BRAF V600E mutation status were derived from previous reports. Comparisons were performed using two-sided chi-square tests. Survival curves were plotted using the Kaplan-Meier method and a multivariate Cox regression analysis was performed to determine hazard ratio (HR).
Results: PIK3CA mutation was present in 107/780 (14%) of CRCs, and these showed significant differences in the following features when compared to CRC lacking a PIK3CA mutation:
|PIK3CA-mutated CRC n = 107||PIK3CA-wildtype CRC n = 673||P Value|
|Proximal Colonic Location||58/105 (55%)||222/418 (35%)||<0.001|
|KRAS Mutation||50/107 (47%)||169/673 (25%)||<0.001|
|Minor Mucinous Component||43/94 (46%)||142/602 (24%)||<0.001|
|Altered MGMT expression||35/97 (36%)||125/631 (20%)||0.001|
|CIMP-High||22/101 (22%)||75/646 (12%)||0.004|