Clinicopathologic Significance of BRAF Mutation and Extracellular Signal Regulated Kinase 1/2 Expression in Patients With a Colorectal Adenocarcinoma.
OBJECTIVE
BRAF mutation and expression of extracellular signal regulated kinase (ERK) are linked with colorectal carcinogenesis through the serrated pathway. BRAF and ERK1/2 play important roles in the activation of mitogen-activated protein (MAP) kinase signaling pathways. The present study investigated the clinicopathologic outcomes of BRAF mutation and ERK1/2 expression in patients with colorectal cancer (CRC) and the possibility of using them as prognostic indicators.


METHODS
Dual-priming oligonucleotide-based multiplex polymerase chain reaction for BRAF (V600E) mutation and immunohistochemical analysis of ERK1/2 were performed using 65 formalin-fixed, paraffin-embedded samples from patients with CRC. We analyzed the dependences of the clinicopathologic features on BRAF mutation and ERK1/2 expression.


RESULTS
Out of 65 samples from CRC patients, BRAF mutation was detected in 3 (4.6%). The 3 patients with BRAF mutation presented with T3 CRC with lymph node metastasis (stage III) showing moderately or poorly differentiated histology. ERK1 and ERK2 were positively detected in 73.8% and 15.4% of the patients with CRC, respectively. ERK1 expression was significantly correlated with lymph node metastasis (P = 0.049). ERK2 expression was significantly correlated with tumor emboli (P < 0.05), tumor invasion (P = 0.035), lymph node metastasis (P = 0.017), and stage (P = 0.02).


CONCLUSIONS
BRAF mutation and ERK1/2 expression may be associated with advanced or more aggressive CRC. These molecular markers might play prognostic roles in CRC developed through the serrated pathway.
Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyung Ook
HO
Kim
Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Beom Gyu
BG
Kim
Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Seong Jae
SJ
Cha
Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Yong Gum
YG
Park
Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea.
Tae Jin
TJ
Lee
Adenocarcinoma; BRAF; Colorectal neoplasms; ERK1; ERK2