Amphiregulin is a promising prognostic marker for liver metastases of colorectal cancer.
OBJECTIVE
Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer.


METHODS
The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner.


RESULTS
Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217).


CONCLUSIONS
AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.
Yamada
Michiyo
M
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Ichikawa
Yasushi
Y
Yamagishi
Shigeru
S
Momiyama
Nobuyoshi
N
Ota
Mitsuyoshi
M
Fujii
Syoichi
S
Tanaka
Kuniya
K
Togo
Shinji
S
Ohki
Shigeo
S
Shimada
Hiroshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D066255:EGF Family of Proteins; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
C587848:AREG protein, human; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins