Linkage of elevated ets-2 expression to hepatocarcinogenesis.
BACKGROUND
Previous studies have shown that ets-2, a transcription factor, is linked to carcinoma progression. In the present study, we investigated the expression and clinical significance of ets-2 in hepatocellular carcinoma (HCC) and malignant transformation of the liver.


METHODS
The expression of ets-2 was immunohistochemically investigated with 91 HCC, 46 noncancerous lesions, 8 atypical adenomatous hyperplasias and 14 normal liver controls.


RESULTS
The ets-2 labeling index (LI) in normal liver was significantly lower than in noncancerous lesion (p<0.0001). The LI in atypical adenomatous hyperplasia tended to be higher than in noncancerous lesion (p=.0779). In HCC, the LI was significantly lower (p<0.0001) than that in noncancerous lesion and atypical adenomatous hyperplasia. In HCC, the ets-2 expression level was significantly lower in cases with advanced stage (p=0.0085), large size (p=0.0441), high proliferating activity (p<0.0001), poor differentiation (p=0.0005), the presence of portal invasion (p=0.0009) and intrahepatic metastasis (p=0.0236) and shorter disease-free survival (p=0.0372).


CONCLUSIONS
These findings suggest that ets-2 plays an important role predominantly in malignant transformation of the liver.
Ito
Yasuhiro
Y
Department of Surgery, Kuma Hospital, Kobe, Japan. ito01@kuma-h.or.jp
Miyoshi
Eiji
E
Takeda
Tsutomu
T
Nagano
Hiroaki
H
Sakon
Masato
M
Noda
Katsuhisa
K
Tsujimoto
Masahiko
M
Monden
Morito
M
Matsuura
Nariaki
N
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012097:Repressor Proteins; D015996:Survival Rate; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; D019394:Ki-67 Antigen; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases