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. 2010 Jun 8;102(12):1762-8.
doi: 10.1038/sj.bjc.6605694. Epub 2010 May 18.

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

Z Saridaki  1 , D Papadatos-Pastos, M Tzardi, D Mavroudis, E Bairaktari, H Arvanity, E Stathopoulos, V Georgoulias, J Souglakos
Affiliations

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

Z Saridaki et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
(A) MLH1(+) adenocarcinoma with moderate differentiation of the colon (original magnification, × 200). (B) MSH2(+) adenocarcinoma with moderate differentiation of the colon (original magnification, × 100). (C) Cyclin D1( +) adenocarcinoma moderate–poorly differentiated (original magnification, × 100).
Figure 2
Figure 2
(A) Progression-free survival in first-line chemotherapy, analysed by BRAF mutation status. (B) Overall survival, analysed by BRAF mutation status.
See this image and copyright information in PMC

References

    1. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260: 812–816 - PubMed
    1. Aaltonen LA, Peltomaki P, Mecklin JP, Jarvinen H, Jass JR, Green JS, Lynch HT, Watson P, Tallqvist G, Juhola M (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54: 1645–1648 - PubMed
    1. Benlloch S, Paya A, Alenda C, Bessa X, Andreu M, Jover R, Castells A, Llor X, Aranda FI, Massuti B (2006) Detection of BRAF V600E mutation in colorectal cancer: comparison of automatic sequencing and real-time chemistry methodology. J Mol Diagn 8: 540–543 - PMC - PubMed
    1. Bhatt KV, Hu R, Spofford LS, Aplin AE (2007) Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Oncogene 26: 1056–1066 - PubMed
    1. Bhatt KV, Spofford LS, Aram G, McMullen M, Pumiglia K, Aplin AE (2005) Adhesion control of cyclin D1 and p27Kip1 levels is deregulated in melanoma cells through BRAF-MEK-ERK signaling. Oncogene 24: 3459–3471 - PubMed

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