Matsumura M, Niwa Y, Kato N, Komatsu Y, Shiina S, Kawabe T, Kawase T, Toyoshima H, Ihori M, Shiratori Y
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hepatology. 1994 Dec;20(6):1418-25. doi: 10.1002/hep.1840200607.
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, alpha-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 alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-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%). alpha-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 alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-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 alpha-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.
由于循环中肿瘤细胞数量极少，我们尝试通过巢式逆转录-聚合酶链反应在外周血核细胞成分中检测与肝细胞相关的mRNA，以检测循环中的肝细胞癌。通过逆转录-聚合酶链反应证实，白蛋白mRNA不仅存在于肝组织（肝细胞）和HepG2细胞中，也存在于正常健康志愿者血液的核细胞（中性粒细胞和淋巴细胞）中。相比之下，甲胎蛋白mRNA存在于肝组织和HepG2细胞中，但在正常健康志愿者的外周血中未检测到，这表明甲胎蛋白mRNA有可能用于在中性粒细胞和淋巴细胞群体中检测良性和恶性肝细胞。33例肝细胞癌患者中有17例（52%）外周血检测到甲胎蛋白mRNA，13例肝硬化患者中有2例（15%），17例慢性肝炎患者中有2例（12%）。26例正常健康志愿者均未检测到甲胎蛋白mRNA（0%）。在肝细胞癌患者中，血液中检测到甲胎蛋白mRNA的患者肿瘤组织总体积、肿瘤最大尺寸和血清甲胎蛋白水平显著升高。此外，所有6例出现肝外器官转移的患者血液中均检测到甲胎蛋白mRNA（100%），而27例无转移患者中有11例（41%）检测到。根据这些结果，我们得出结论，外周血中甲胎蛋白mRNA的存在可能是循环中恶性或良性肝细胞的一个指标，这可能预测肝细胞癌患者肿瘤细胞的血行播散转移。
