Correlation between Midkine Protein Overexpression in Hepatocellular Carcinoma with the Presence of Tumor Cells in Circulating Blood

OBJECTIVE To investigate midkine (MK) protein expression in human hepatocellular carcinoma (HCC) and its relation to dissemination of cancer cells in blood.

METHODS Circulating tumor cells were detected in preoperative blood samples using reverse transcription polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) mRNA. Midkine expression was immunohistochemically examined in surgically resected HCC tissues.

RESULTS Forty-one HCC patients with positive serum AFP were studied. Positive AFP mRNA expression was shown in 18 preoperative blood samples (43.9%) and midkine overexpression was detected in 29 excised tumors (70.7%). Among the 29 patients, 18 (62.1%) showed positive AFP mRNA in their preoperative blood samples. In contrast, the positive AFP mRNA expression was only observed in 3 out of 12 patients (25.0%) without aberrant midkine expression. Statistical analysis showed that abnormal midkine expression in the tumors was a variant significantly associated with the presence of tumor cells in the blood circulation (P<0.05).

CONCLUSION In human hepatocellular carcinoma, midkine overexpression is correlated with a haematogenuous spread of the primary tumor cells, and it may be a marker for tumor metastatic potential.