Supplementary Material for: Expression of c-Met in Primary and Recurrent Hepatocellular Carcinoma

<b><i>Background:</i></b>The clinical course of hepatocellular carcinoma (HCC) is complicated, because it often recurs and shows multiple lesions, some of which progress to a more malignant form, shortening the life of the patient. The hepatocyte growth factor receptor c-Met has been shown to play an important role in the pathogenesis of HCC, but the influence of c-Met expression on the clinical course of HCC remains to be fully elucidated. <b><i>Methods:</i></b>We randomly selected and included 600 tumor specimens obtained from the primary and recurrent lesions of 319 HCC cases between 1995 and 2007. The expression of c-Met was determined by immunohistochemistry using archived formalin-fixed paraffin-embedded samples. We analyzed the correlation between c-Met expression and clinical parameters, including survival. In addition, we examined c-Met expression in the malignant transition of HCC in all cases including recurrent lesions. <b><i>Results:</i></b>Survival analysis using the multivariate Cox proportional-regression model revealed that the prognosis was significantly better in the primary cases with high c-Met expression than in those with low c-Met expression (hazard ratio 0.159, 95% confidence interval 0.065–0.391; <i>p</i> &lt; 0.001). During the course of recurrence, some cases with high c-Met expression returned to low c-Met expression. Among 40 cases with high c-Met expression, 29 survived more than 2 years after detecting the high c-Met expression. <b><i>Conclusion:</i></b>High expression of c-Met may be a prognostic factor for a good, rather than a poor, HCC prognosis. The involvement of c-Met expression in the malignant transition of recurrent HCC is obscure.

<i>背景：</i>肝细胞癌（hepatocellular carcinoma, HCC）的临床病程复杂，常出现复发并呈现多病灶表现，部分病灶可进展为更高恶性程度的表型，缩短患者生存期。已有研究证实肝细胞生长因子受体c-Met（hepatocyte growth factor receptor c-Met）在肝细胞癌的发病机制中发挥重要作用，但c-Met表达对肝细胞癌临床病程的影响仍有待全面阐明。
<i>方法：</i>本研究于1995年至2007年间，随机选取并纳入319例肝细胞癌患者的原发灶与复发灶标本共计600份。采用存档的福尔马林固定石蜡包埋组织样本，通过免疫组化法检测c-Met的表达水平。本研究分析了c-Met表达与包括生存期在内的临床参数之间的相关性；此外，还针对所有病例（含复发灶）检测了肝细胞癌恶性转化过程中的c-Met表达情况。
<i>结果：</i>采用多因素Cox比例风险回归模型进行生存分析显示，c-Met高表达的原发灶病例预后显著优于c-Met低表达病例（风险比0.159，95%置信区间0.065~0.391；P<0.001）。在复发病程中，部分c-Met高表达病例的表达水平可回落至低表达状态。在40例c-Met高表达病例中，有29例在检测到高表达状态后生存期超过2年。
<i>结论：</i>c-Met高表达或可作为肝细胞癌预后良好的预测因子，而非不良预后的指标；c-Met表达在复发性肝细胞癌恶性转化中的作用仍不明确。