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. 2011 Oct 15;117(20):4623-32.
doi: 10.1002/cncr.26086. Epub 2011 Mar 31.

Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer

Ben Tran  1 , Scott Kopetz, Jeanne Tie, Peter Gibbs, Zhi-Qin Jiang, Christopher H Lieu, Atin Agarwal, Dipen M Maru, Oliver Sieber, Jayesh Desai
Affiliations

Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer

Ben Tran et al. Cancer. .

Abstract

Background: It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC.

Methods: By using prospective clinical data and molecular analyses from 2 major centers (Royal Melbourne Hospital and The University of Texas MD Anderson Cancer Center), patients with known BRAF mutation status were analyzed for clinical characteristics, survival, and metastatic sites.

Results: The authors identified 524 metastatic CRC patients where BRAF mutation status was known; 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right-sided primary tumor, MSI, and poorer survival (median, 10.4 months vs 34.7 months, P < .001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049). In additional survival analyses, MSI tumors had significantly poorer survival compared with microsatellite stable tumors (22.1 months vs 11.1 months, P = .017), but this difference was not evident in the BRAF mutant population.

Conclusions: The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. The authors demonstrated that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation.

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Figures

Figure 1a
Figure 1a
Overall Survival: BRAF mutant tumors versus BRAF wild-type tumors
Figure 1b
Figure 1b
Overall Survival: BRAF mutant tumors versus BRAF wild-type tumors in population-based cohort
Figure 1c
Figure 1c
Overall Survival: BRAF mutant tumors versus BRAF wild-type tumors in trial-screened cohort
Figure 1d
Figure 1d
Overall survival: RMH versus MDACC
Figure 2a
Figure 2a
Overall Survival: MSS tumors versus MSI tumors
Figure 2b
Figure 2b
Overall Survival: MSS versus MSI in BRAF mutant tumors
Figure 2c
Figure 2c
Overall Survival: MSS versus MSI in BRAF wild-type tumors
Figure 2d
Figure 2d
Overall Survival: BRAF mutant versus BRAF wild-type in MSI tumors
Figure 2e
Figure 2e
Overall Survival: BRAF mutant versus wild-type in MSS tumors
See this image and copyright information in PMC

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