PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer

Abstract

PURPOSE PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little has been known on the prognostic role of PIK3CA mutation in colon cancer. METHODS Utilizing 450 resectable colon cancers (stage I-III) in two independent prospective cohorts, we detected PIK3CA mutation in 82 (18%) tumors by Pyrosequencing. Cox proportional hazard models were used to calculate hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI) and KRAS and BRAF mutation. RESULTS Compared to patients with PIK3CA-wild-type tumors, those with PIK3CA-mutated tumors experienced an increase in colon-cancer specific mortality by the univariate analysis [HR 1.64; 95% confidence interval (CI), 0.95-2.86], which persisted after adjusting for other known or potential risk factors for cancer recurrence (multivariate HR 2.23, 95% CI, 1.21-4.11). The effect of PIK3CA mutation on cancer survival appeared to differ according to KRAS-mutational status. Among patients with KRAS-wild-type tumors, the presence of PIK3CA mutation was associated with a significant increase in colon cancer-specific mortality (HR 3.80, 95% CI, 1.56-9.27). In contrast, PIK3CA mutation conferred no significant effect on mortality among patients with KRAS-mutated tumors (HR 1.25; 95% CI, 0.52-2.96), although the interaction was not statistically significant (Pinteraction=0.13). CONCLUSION Among patients who undergo a curative resection of colon cancer, PIK3CA mutation is associated with shorter cancer-specific survival. The adverse effect of PIK3CA mutation may be potentially limited to patients with KRAS-wild-type tumors.

Oncogenic mutations as predictive factors in colorectal cancer

“…These findings do not provide any evidence for a strong role of PIK3CA mutations as a single marker for prediction of resistance to cetuximab in chemorefractory patients. Nevertheless, PIK3CA mutation seems to be a prognostic marker both in colon and rectal cancers (He et al, 2009;Ogino et al, 2009c). Several studies have thus assessed PIK3CA mutations in association with loss of PTEN expression, as PTEN has an important role as a tumour-suppressor protein that antagonizes PI3K function.…”

Mutación del gen KRAS en el cáncer de colon y recto

“…En la actualidad son centenares de trabajos en los que se han determinado el status de algunos de estos genes como EGFr, KRAS, BRAK, PIP3K, etc. [16][17][18] , siendo su estudio rutinario en la evaluación de pacientes con cáncer colo-rectal en la mayoría de los centros extranjeros y en algunos centros privados nacionales 12,19,20 . A pesar de esta realidad, los estudios a nivel genético y molecular en el cáncer de colon y recto en nuestro medio, son recientes y escasos [21][22][23][24][25][26][27] .…”

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

“…PRIMA-1 MET is the only drug currently under clinical trials targeting mutant p53 (93). Mutation in PIK3CA gene has also been associated with poorer prognosis in human cancer (94)(95)(96). However, no conclusive data are reported for HNSCC (66,97).…”