Suppressed MKP-1 is an independent predictor of outcome in patients with hepatocellular carcinoma.
OBJECTIVE
An increase in the activity of mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vivo. This study was designed to clarify the expression of MKP-1 in surgically resected hepatocellular carcinoma (HCC).


METHODS
We reviewed the cases of 77 patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on paraffin-embedded tissues. The correlation between MKP-1 expression and clinical outcome was investigated.


RESULTS
Tumor cells were immunohistochemically stained for MKP-1 expression, and the same levels as in normal hepatocytes were detected in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1 expression significantly correlated with serum alpha-fetoprotein levels and tumor size (p<0.05). The disease-free survival rates in MKP-1-negative and -positive patients were 0 and 31.0% at 5 years, respectively (p<0.01). The survival rates after a surgical resection in MKP-1-negative and -positive patients were 18.2 and 65.5% at 5 years, respectively (p<0.01).


CONCLUSIONS
The MKP-1 expression in HCC was an independent prognostic factor for outcome in HCC patients. In the future, it will be useful to explore whether the phosphatase expression might account for the response to HCC treatments targeting at MAPK activation.
Tsujita
Eiji
E
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. tsujita@surg2.med.kyushu-u.ac.jp
Taketomi
Akinobu
A
Gion
Tomonobu
T
Kuroda
Yousuke
Y
Endo
Kazuya
K
Watanabe
Akihiro
A
Nakashima
Hideaki
H
Aishima
Shin-ichi
S
Kohnoe
Shunji
S
Maehara
Yoshihiko
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D015536:Down-Regulation; D054638:Dual Specificity Phosphatase 1; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D000509:alpha-Fetoproteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases