Nuclear beta-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma.
Beta-catenin is a component of the Wingless/Wnt signaling pathway and can activate target genes associated with proliferation and invasion, linking with the APC gene. The purpose of this study was to investigate whether nuclear expression of beta-catenin in cells at the invasive front or in the vessels was associated with liver metastasis in human colon cancer.


METHODS
One hundred and eighteen patients with colorectal carcinoma who underwent surgical resection (45 patients with liver metastasis and 73 patients without liver metastasis at least 5 years after surgery) were included in the study. Proliferative activity was determined in several areas (tumor center, invasive front and in the vessels) by immunohistochemistry and whether it was correlated with liver metastasis was examined.


RESULTS
In 73.1% of primary tumors, positive staining for beta-catenin was detected in the membranes at the tumor center and in the nuclei at the invasive front. In 32 patients (26.9% of all cases), beta-catenin was expressed exclusively in the nuclei of the carcinoma cells throughout the tumors. Significant differences in expression of nuclear beta-catenin in the primary tumors were detected between the liver metastasis and non-liver metastasis groups at the tumor center (p=0.004), invasive front (p=0.021) and in the vessels (p<0.0001).


CONCLUSIONS
Nuclear accumulation of beta-catenin in cellular cells at the invasive front and in the vessels was the most powerful predictor of liver metastasis in colorectal cancer. This may be an important marker in the selection of patients for adjuvant therapy or other treatment modalities.
Suzuki
Hideki
H
Department of General Surgical Science (Surgery I), Gunma University Graduate School of Medicine, Maebashi, Japan. hidesu@med.gunma-u.ac.jp
Masuda
Norihiro
N
Shimura
Tatsuo
T
Araki
Kenichi
K
Kobayashi
Tsutomu
T
Tsutsumi
Soichi
S
Asao
Takayuki
T
Kuwano
Hiroyuki
H
D015820:Cadherins / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D051178:alpha Catenin / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis*
D015820:Cadherins; D051178:alpha Catenin; D051176:beta Catenin