title: KRAS and BRAF mutations in anal carcinoma.
abstract: The EGF receptor (EGFR) is expressed in most cases of anal carcinomas. Anecdotal benefit from EGFR-targeted therapy has been reported in anal cancer and a negative correlation with Kirsten Ras (KRAS) mutation status has been proposed. The purpose of this retrospective study was to investigate the frequency and the prognostic value of KRAS and BRAF mutations in a large cohort of patients with anal cancer. One hundred and ninety-three patients with T1-4N0-3M0-1 anal carcinoma were included in the study. Patients were treated with curative (92%) or palliative intent (8%) between January 2000 and January 2010. KRAS mutations were detected using Therascreen(®)KRAS real-time PCR assay (Qiagen) and V600E or V600D/K BRAF mutations were uncovered using Pyrosequencing. The frequency of KRAS and BRAF mutations was low; KRAS mutations were detected in 1.6% and BRAF mutations in 4.7% of the biopsies. No impact of KRAS or BRAF status on survival was found. In conclusion, both KRAS and BRAF mutations are rare in anal cancer. The low frequency of KRAS mutations support protocols exploring EGFR-targeted therapy in patients with metastatic anal cancer, while treatment with BRAF inhibitors might be relevant for only a very few patients.
authors.affiliation: Department of Oncology, Herlev Hospital, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Serup-Hansen
authors.forename: Dorte
authors.initials: D
authors.lastname: Linnemann
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.forename: Poul Flemming
authors.initials: PF
authors.lastname: Geertsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Havsteen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D018289:Carcinoma, Verrucous / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Anal cancer; BRAF; KRAS; prognosis; survival