N-myc downstream regulated gene 1 (NDRG1)/Cap43 enhances portal vein invasion and intrahepatic metastasis in human hepatocellular carcinoma.
N-myc downstream regulated gene 1 (NDRG1)/Cap43 is a 43 kDa protein that is widely distributed in the body. Its expression is regulated by nickel, cobalt, hypoxic condition and others; it is reported to be weaker in tumors than normal tissues; and NDRG1/Cap43 is considered to act suppressively to tumor metastasis. This current study immunohistochemically examined NDRG1/Cap43 expression in hepatocellular carcinoma (HCC), and analyzed its relationship to clinicopathologic factors and prognosis. The samples were 105 surgically resected HCC tissue blocks, i.e., 18 well-differentiated HCC, 61 moderately differentiated HCC, 10 poorly differentiated HCC, 9 'nodule-in-nodule' type HCC, and 7 sarcomatous HCC. In all cases, NDRG1/Cap43 was not expressed in normal liver cells. Strong expression was found in 65 of the 105 cases (62%), i.e., in 11.1% of well-differentiated HCC, 72.1% of moderately differentiated HCC, 80.0% of poorly differentiated HCC, and 71.4% of sarcomatous HCC. In the 'nodule-in-nodule' type, its expression was found in 55.6% of their well-differentiated component, and this frequency was significantly higher than that in well-differentiated HCC (11.1%). In the cases showing strong NDRG1/Cap43 expression, frequency of portal vein invasion and of intrahepatic metastasis was significantly high. No clear relationship between the expression and prognosis was observed. NDRG1/Cap43 expression that was found in advanced HCC was thought to accelerate tumor invasion and metastasis. NDRG1/Cap43 could act as a useful biomarker of HCC.
Akiba
Jun
J
Department of Pathology, Kurume University School of Medicine, Fukuoka 830-0011, Japan. akiba@med.kurume-u.ac.jp
Ogasawara
Sachiko
S
Kawahara
Akihiko
A
Nishida
Naoyo
N
Sanada
Sakiko
S
Moriya
Fukuko
F
Kuwano
Michihiko
M
Nakashima
Osamu
O
Yano
Hirohisa
H
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000502:physiology*; D002454:Cell Differentiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011169:Portal Vein / Q000473:pathology*; D011379:Prognosis; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein