PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival

Rosty C, Young JP, Walsh MD, Clendenning M, Sanderson K, Walters RJ, Parry S, Jenkins MA, Win AK, Southey MC, Hopper JL, Giles GG, Williamson EJ, English DR, Buchanan DD (2013) PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival. PLoS One 8:e65479

Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident tumors from the Melbourne Collaborative Cohort Study. The status of O-6-methylguanine-DNA methyltransferase (MGMT) was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability, CpG island phenotype (CIMP), KRAS and BRAF V600E mutation status, and pathology review features were derived from previous reports. PIK3CA mutation was observed in 105 of 757 (14%) of carcinomas, characterized by location in the proximal colon (54% vs. 34%; P<0.001) and="" an="" increased="" frequency="" of="" kras="" mutation="" (48%="" vs.="" 25%;=""><0.001). high-levels="" of="" cimp="" were="" more="" frequently="" found="" in="" pik3ca-mutated="" tumors="" compared="" with="" pik3ca="" wild-type="" tumors="" (22%="" vs.="" 11%;="" p="0.004)." there="" was="" no="" difference="" in="" the="" prevalence="" of="" braf="" v600e="" mutation="" between="" these="" two="" tumor="" groups.="" pik3ca-mutated="" tumors="" were="" associated="" with="" loss="" of="" mgmt="" expression="" (35%="" vs.="" 20%;="" p="0.001)" and="" the="" presence="" of="" tumor="" mucinous="" differentiation="" (54%="" vs.="" 32%;=""><0.001). in="" patients="" with="" wild-type="" braf="" tumors,="" pik3ca="" mutation="" was="" associated="" with="" poor="" survival="" (hr="" 1.51="" 95%="" ci="" 1.04-2.19,="" p="0.03)." in="" summary,="" pik3ca-mutated="" colorectal="" carcinomas="" are="" more="" likely="" to="" develop="" in="" the="" proximal="" colon,="" to="" demonstrate="" high="" levels="" of="" cimp,="" kras="" mutation="" and="" loss="" of="" mgmt="" expression.="" pik3ca="" mutation="" also="" contributes="" to="" significantly="" decreased="" survival="" for="" patients="" with="" wild-type="" braf="">