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Does Percutaneous Liver Biopsy of Hepatocellular Carcinoma Cause Hematogenous Dissemination? An In Vivo Study with Quantitative Assay of Circulating Tumor DNA Using Methylation-Specific Real-Time Polymerase Chain Reaction

¹ Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, New Territories, Hong Kong SAR.
² Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
³ Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
⁴ Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
⁵ Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.

OBJECTIVE. Our purpose was to find out whether percutaneous biopsy of hepatocellular carcinoma will cause significant dissemination of tumor into the circulation by quantitative analysis of circulating tumor DNA.

SUBJECTS AND METHODS. In this prospective study of 32 patients with suspected hepatocellular carcinoma who underwent sonographically guided liver biopsy, a peripheral venous blood sample was obtained before and 5 min after the procedure. Biopsy was performed using an 18-gauge biopsy gun. DNA was extracted from the plasma of the blood samples for methylation-specific polymerase chain reaction. Quantitative measures of the plasma tumor DNA were determined with real-time quantitative polymerase chain reaction, and the amount was expressed as a methylation index (%) in plasma.

RESULTS. Nineteen (59.4%) of 32 patients did not have detectable p16 tumor suppressor gene marker (p16M) in plasma before biopsy, and they showed no detectable plasma p16M after biopsy. Thirteen (65%) of 20 patients had p16M identified in the plasma before liver biopsy. Quantitative analysis of the plasma tumor DNA in these 13 patients showed no statistically significant difference in the methylation index before and after biopsy (p = 0.345, Wilcoxon's signed rank test).

CONCLUSION. No evidence exists that percutaneous liver biopsy results in hematogenous dissemination of hepatocellular carcinoma as shown by quantitative analysis of circulating tumor DNA (p16M) using methylation-specific real-time polymerase chain reaction.

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