[725] 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 = 107PIK3CA-wildtype CRC n = 673P Value
Proximal Colonic Location58/105 (55%)222/418 (35%)<0.001
KRAS Mutation50/107 (47%)169/673 (25%)<0.001
Minor Mucinous Component43/94 (46%)142/602 (24%)<0.001
Altered MGMT expression35/97 (36%)125/631 (20%)0.001
CIMP-High22/101 (22%)75/646 (12%)0.004


There was no significant overlap with BRAF V600E mutation (P=0.52). Patients with PIK3CA-mutated CRC had significantly poorer overall survival than those with PIK3CA wild-type CRC when BRAF-mutated CRC were excluded from the analysis (P=0.015; Log Rank Test; HR=1.51 95% CI 1.08 – 2.12).


Conclusions: PIK3CA-mutated CRCs are more likely to be located in the proximal colon and to demonstrate CIMP-high and KRAS mutations but not BRAF mutation. Among patients with wild-type BRAF CRC, PIK3CA mutation was associated with overall poorer survival.
Category: Gastrointestinal

Monday, March 4, 2013 1:00 PM

Poster Session II # 129, Monday Afternoon

 

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