J Korean Med Sci.  2017 Jan;32(1):38-46. 10.3346/jkms.2017.32.1.38.

BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status

• Jang MH
• Kim S
• Hwang DY
• Kim WY
• Lim SD
• Kim WS
• Hwang TS
• Han HS

• KMID: 2417583
• DOI: http://doi.org/10.3346/jkms.2017.32.1.38

Abstract

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.

Keyword

BRAF V600E; Colorectal Cancer; Clinicopathological Feature; Microsatellite Instability

MeSH Terms

Colorectal Neoplasms*
Humans
Incidence
Microsatellite Instability*
Microsatellite Repeats*
Mucins
Mucins

Figure

• 

  Fig. 1 Histopathological features of CRCs. (A) CRC with positive tumor budding (arrow, ≥ 5 buds). (B) CRC with a marked peritumoral lymphoid reaction and tumor cell destruction by infiltrating lymphocytes. (C) CRC with an active Crohn-like lymphoid reaction (≥ 1-mm-sized lymphoid aggregate). (D) Mucinous component. (E) Signet ring cell component. (F) Medullary component. (G) Serrated component. (H) Cribriform-comedo component. Stain, hematoxylin-eosin; original magnification: 1.25× (C), 40× (B, F, H), 100× (A, D, G), 400× (E, inset of B, inset of G). CRC = colorectal cancer.

• 

  Fig. 2 Comparison of overall survival between patients with BRAF V600E-mutated CRC and those with wild-type CRC among 327 cases of primary CRC. CRC = colorectal cancer.

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