Yeh Chun-Nan, Pang See-Tong, Wu Ren-Ching, Chen Tsung-Wen, Jan Yi-Yin, Chen Miin-Fu
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.
Oncol Rep. 2009 Jan;21(1):49-56.
Cholangiocarcinoma (CCA), a lethal malignancy afflicting many thousands of patients throughout the world, develops through a multi-step progression. We have established an oral thioacetamide-induced model of rat CCA recapitulating the histologic progression of human CCA, especially for mass-forming CCA (MF-CCA). Our previous DNA microarray study showed MUC4 is overexpressed in rat CCA. Herein, we investigated the prognostic value of MUC4 for predicting overall survival rate (OS) for MF-CCA patients undergoing hepatectomy. Overexpression of MUC4 in rat CCA is demonstrated by RT-PCR. From the archives of Chang Gung Memorial Hospital, 53 MF-CCA patients undergoing hepatectomy were selected for an immunohistochemical study of MUC4. Fifteen clinicopathological variables (including MUC4 staining status) were used for survival analysis. MUC 4 is overexpressed in rat CCA. Fifty-three MF-CCA patients, 26 men and 27 women, with a median age of 60 years (range: 29-89) were studied. During the median follow-up duration of 14.7 months, the OS rates at 1, 3, and 5 years were 58.8, 25.5, and 16.5%, respectively. Univariate analysis showed that an absence of physical findings, better nutritional status, small tumor size, negative lymph node metastasis, an absence of MUC4 staining, and curative hepatic resection were associated with favorable OS rate for MF-CCA patients after hepatectomy. However, multivariate Cox proportional hazard analysis showed that an absence of MUC4 staining, small tumor size, and curative hepatectomy independently predicted MF-CCA patients with favorable OS rate after hepatectomy. In conclusion, an absence of MUC4 staining, small tumor size, and curative hepatectomy could independently predict MF-CCA patients with favorable OS rate after hepatectomy.
胆管癌（CCA）是一种致命的恶性肿瘤，全球有成千上万的患者受其折磨，它通过多步骤进展而发展。我们建立了一种口服硫代乙酰胺诱导的大鼠CCA模型，该模型再现了人类CCA的组织学进展，特别是对于肿块形成性CCA（MF-CCA）。我们之前的DNA微阵列研究表明，MUC4在大鼠CCA中过表达。在此，我们研究了MUC4对接受肝切除术的MF-CCA患者总生存率（OS）预测的预后价值。通过RT-PCR证实了MUC4在大鼠CCA中的过表达。从长庚纪念医院的档案中，选择了53例接受肝切除术的MF-CCA患者进行MUC4的免疫组织化学研究。15个临床病理变量（包括MUC4染色状态）用于生存分析。MUC4在大鼠CCA中过表达。研究了53例MF-CCA患者，其中男性26例，女性27例，中位年龄60岁（范围：29 - 89岁）。在中位随访期14.7个月期间，1年、3年和5年的OS率分别为58.8%、25.5%和16.5%。单因素分析显示，无体格检查异常、营养状况较好、肿瘤体积小、无淋巴结转移、无MUC4染色以及根治性肝切除与肝切除术后MF-CCA患者的良好OS率相关。然而，多因素Cox比例风险分析显示，无MUC4染色、肿瘤体积小和根治性肝切除独立预测肝切除术后MF-CCA患者具有良好的OS率。总之，无MUC4染色、肿瘤体积小和根治性肝切除可独立预测肝切除术后MF-CCA患者具有良好的OS率。
