Expression of the midkine gene in human hepatocellular carcinomas.
OBJECTIVE
Aberrant expression of Midkine (MK) has been found in various human carcinomas including hepatocellular carcinoma (HCC). The aim of study is to identify the incidence of MK expression in tumor and surrounding non-tumor tissues of the liver, and to find the correlation of MK expression with other tumor markers.


METHODS
Liver tissues were obtained from 16 patients with HCC and 4 with metastatic liver cancer. Background diseases of the HCC patients include liver cirrhosis and chronic hepatitis of type B or C. RNA was prepared from both cancerous and surrounding non-cancerous tissues, and analyzed for the presence of MK mRNA by RT-PCR, PCR-Southern blot, and Northern blot analysis.


RESULTS
MK expression was detected in 12 (75%) of 16 HCCs by PCR-Southern blot analysis, the most sensitive of the 3 methods. Three of 9 surrounding cirrhotic tissues were weakly positive for MK expression, and none of chronic hepatitis and 4 normal tissues were negative. No significant difference was found in clinical and pathological parameters between MK negative and positive cases. Among metastatic cancers, 1 of gastric origin was positive for MK expression, but 1 each of chorangiocellular, gall bladder, and gastrinoma origin was negative.


CONCLUSIONS
These results suggest that MK is expressed in the majority of HCC tissues and rarely in surrounding tissues in chronic liver diseases.
Koide
N
N
First Department of Internal Medicine, Okayama University School of Medicine, Japan. koide@hospital.okayama-u.ac.jp
Hada
H
H
Shinji
T
T
Ujike
K
K
Hirasaki
S
S
Yumoto
Y
Y
Hanafusa
T
T
Kadomatsu
K
K
Muramatsu
H
H
Muramatsu
T
T
Tsuji
T
T
D000368:Aged; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000078792:Midkine