Detection of α-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: A possible predictor of metastatic hepatocellular carcinoma

Authors

  • Masayuki Matsumura M.D.,

    Corresponding author
    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    • Masayuki Matsumura, M.D., Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113, Japan
    Search for more papers by this author
  • Yasuro Niwa,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Naoya Kato,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Yutaka Komatsu,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Shuichiro Shiina,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Takao Kawabe,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Takeo Kawase,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Hiroshi Toyoshima,

    1. Department of Gastroenterology and Hepatology, Japanese Red Cross Medical Center, 4–1–22 Hiroo, Shibuya-ku, Tokyo 150, Japan
    Search for more papers by this author
  • Masashi Ihori,

    1. Department of Gastroenterology and Hepatology, Japanese Red Cross Medical Center, 4–1–22 Hiroo, Shibuya-ku, Tokyo 150, Japan
    Search for more papers by this author
  • Yasushi Shiratori,

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author
  • Masao Omata

    1. Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113
    Search for more papers by this author

Abstract

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription—polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription—polymerase chain reaction. In contrast, α-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using α-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. α-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). α-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum α-fetoprotein level were markedly increased in the patients with α-fetoprotein mRNA in blood. In addition, α-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of α-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma. (Hepatology 1994;20:1418–1425).

Ancillary