1. Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy
- Author
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Janine M. Davies, Dimitri G. Trembath, William K. Funkhouser, Allison M. Deal, Timothy Finnegan, Bert H. O'Neil, Joel E. Tepper, Karen E. Weck, and Benjamin F. Calvo
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Oncology ,Male ,endocrine system diseases ,Colorectal cancer ,medicine.medical_treatment ,Biopsy ,DNA Mutational Analysis ,medicine.disease_cause ,0302 clinical medicine ,Registries ,Stage (cooking) ,Phosphorylation ,Rectal cancer ,Extracellular Signal-Regulated MAP Kinases ,Aged, 80 and over ,0303 health sciences ,Mutation ,medicine.diagnostic_test ,Chemoradiotherapy ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunohistochemistry ,Treatment Outcome ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Female ,KRAS ,phosphoAKT ,lcsh:Medical physics. Medical radiology. Nuclear medicine ,Adult ,medicine.medical_specialty ,radiation response ,lcsh:R895-920 ,phosphoERK ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,neoplasms ,030304 developmental biology ,Aged ,Retrospective Studies ,business.industry ,Rectal Neoplasms ,Research ,Sequence Analysis, DNA ,medicine.disease ,digestive system diseases ,Radiation therapy ,Genes, ras ,Cancer research ,ras Proteins ,business ,Proto-Oncogene Proteins c-akt ,KRAS analysis - Abstract
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.
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