Association between recurrence of hepatocellular carcinoma and α-fetoprotein messenger RNA levels in peripheral blood

Association between recurrence of hepatocellular carcinoma and α-fetoprotein messenger RNA levels in peripheral blood
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DOI:
10.1007/s00595-005-3077-5
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发表时间:
2005-12-01
期刊:
影响因子:
2.5
通讯作者:
Monden, M
Monden, M
中科院分区:
医学4区
文献类型:
--
作者:
Morimoto, O;Nagano, H;Monden, M

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目的。肝内和肝外复发是常见的,即使在治愈性肝细胞癌(HCC)切除后,提示术前或术中肿瘤细胞播散。甲胎蛋白(AFP)逆转录聚合酶链反应(RT-PCR)用于检测循环肝癌细胞。我们之前开发了一种定量方法,可以通过实时PCR估计AFP mRNA的水平。在本研究中,我们采用该方法测定HCC切除术前后的AFP mRNA水平,并将其与各种临床病理特征和预后进行比较。我们前瞻性地检查了38例HCC患者的外周血样本和其中25例患者的骨髓抽吸。作为对照,我们检查了20例良性疾病患者的骨髓。随访时间为32 ~ 66个月。采用Real-time RT-PCR检测AFP mRNA水平。38例外周血中有9例(23.7%)表达AFP。AFP mRNA的检测与原发性手术后肝外转移及较短的无病生存期显著相关(P = 0.0245)。如果骨髓样本中AFP mRNA的表达水平高于对照组的最大表达水平,则将其定义为阳性,因为在20个对照骨髓样本中,只有1个(5%)的AFP mRNA表达水平较低。使用这个截止水平,25例HCC患者中有12例(48%)的AFP mRNA呈阳性。骨髓RT-PCR结果与预后的临床病理特征无相关性。实时荧光定量PCR检测血液中而非骨髓中AFP mRNA水平,可用于预测术后肿瘤复发。
Purpose. Intra- and extrahepatic recurrence is common, even after curative resection for hepatocellular carcinoma (HCC), suggesting preoperative or intraoperative tumor cell dissemination. Reverse transcription - polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) is used to detect circulating liver cancer cells. We previously developed a quantitative method that allows estimation of the AFP mRNA level by real-time PCR. In the present study, we used this method to measure the AFP mRNA level before and after resection of HCC, then correlated the findings with various clinicopathological characteristics and prognosis.Methods. We prospectively examined peripheral blood samples from 38 patients with HCC, and bone marrow aspirate from 25 of these patients. As a control, we examined bone marrow from 20 patients with benign diseases. The follow-up period ranged from 32 to 66 months. Real-time RT-PCR was used to detect AFP mRNA levels in the samples.Results. AFP was expressed in 9 (23.7%) of the 38 peripheral blood samples. The detection of AFP mRNA was significantly correlated with extrahepatic metastasis after primary surgery, and a shorter disease-free survival time (P = 0.0245 each). Bone marrow samples were defined as positive if they expressed AFP mRNA at levels higher than the maximum expressed level in the controls, because only 1 (5%) of the 20 control bone marrow samples had low AFP mRNA expression. Using this cutoff level, 12 (48%) of the 25 patients with HCC had positivity for AFP mRNA. The results of bone marrow RT-PCR did not correlate with the clinocopathological characteristics of prognosis.Conclusions. Using real-time PCR to measure the AFP mRNA level in blood, but not bone marrow, could be useful for predicting postoperative tumor recurrence.