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Background   KRAS  mutations may predict poor response to radiotherapy. Downstream events from  KRAS , such as activation of  BRAF , AKT and ERK, may also confer prognostic information but have not been tested in rectal cancer (RC). Our objective was to explore the relationships of  KRAS  and  BRAF  mutation status with p-AKT and p-ERK and outcomes in RC.    Methods  Pre-radiotherapy RC tumor biopsies were evaluated.  KRAS  and  BRAF  mutations were assessed by pyrosequencing; p-AKT and p-ERK expression by immunohistochemistry.    Results  Of 70 patients, mean age was 58; 36% stage II, 56% stage III, and 9% stage IV. Responses to neoadjuvant chemoradiotherapy: 64% limited, 19% major, and 17% pathologic complete response. 64% were  KRAS  WT, 95% were  BRAF  WT. High p-ERK levels were associated with improved OS but not for p-AKT. High levels of p-AKT and p-ERK expression were associated with better responses.  KRAS  WT correlated with lower p-AKT expression but not p-ERK expression. No differences in OS, residual disease, or tumor downstaging were detected by  KRAS  status.    Conclusions   KRAS  mutation was not associated with lesser response to chemoradiotherapy or worse OS. High p-ERK expression was associated with better OS and response. Higher p-AKT expression was correlated with better response but not OS.

Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy