BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome (Journal article)

Saridaki, Z./ Papadatos-Pastos, D./ Tzardi, M./ Mavroudis, D./ Bairaktari, E./ Arvanity, H./ Stathopoulos, E./ Georgoulias, V./ Souglakos, J.


BACKGROUND: The significance of BRAF mutations, microsatelite instability (MSI) status and cyclin D1 expression in patients with metastatic colorectal cancer (mCRC) was evaluated. METHODS: Primary tumours from 144 patients treated for mCRC were assessed for BRAF (V600E) mutation, MSI status and cyclin D1. The data were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: BRAF mutations were detected in 10 (out of 22, 45%) patients with MSI-H tumours compared with 2 (out of 122, 1.6%) in those with microsatellite stable tumours (P<0.001). The presence of BRAF mutations was correlated with cyclin D1 overexpression (7 out of 26 patients, 58% vs 5 out of 118 patients, 14%; P=0.001). Patients with BRAF-mutated primary tumours had a significantly decreased PFS (2.7 vs 9.8 months; P<0.001) and median OS (14 vs 30 months; P<0.001) than patients with wild-type (wt) tumours. Patients with MSI-H and BRAF-mutated tumours experienced significantly lower PFS (3.1 vs 11.4 months; P=0.008) and OS (14.5 vs 35.5 months; P=0.004) than patients with MSI-H and BRAF wt tumours. Similarly, BRAF mutations and cyclin D1 overexpression were correlated with decreased PFS (3.1 vs 8.6 months; P=0.03) and OS (17.8 vs 39.2 months; P=0.01). CONCLUSION: BRAF V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Aged,Aged, 80 and over,Colorectal Neoplasms/drug therapy/*genetics/mortality/pathology,Cyclin D1/*metabolism,Disease-Free Survival,Female,Humans,Male,*Microsatellite Instability,Middle Aged,*Mutation,Neoplasm Metastasis,Prognosis,Proto-Oncogene Proteins B-raf/*genetics
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/23402
ISSN: 1532-1827
Link: http://www.ncbi.nlm.nih.gov/pubmed/20485284
http://www.nature.com/bjc/journal/v102/n12/pdf/6605694a.pdf
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