Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma
Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma
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DOI：
10.3760/cma.j.issn.0366-6999.20121235
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发表时间：
2013-08-20
影响因子：
6.1
通讯作者：
Chen Xiao-ping
中科院分区：
文献类型：
--
作者：
Yan Xue-qiang;Zhang Wei;Chen Xiao-ping
Smad 4在许多癌症中存在突变。它在调节TGF-8信号通路中起肿瘤抑制剂的作用。为探讨Smad 4在肝内胆管癌（intrahepatic cholangiocarcinoma，ICC）组织中的表达及其与ICC生物学行为和预后的关系，采用免疫组化方法检测49例ICC组织和9例正常肝组织中Smad 4的表达。结果Smad 4在正常肝组织中的阳性表达率为100%，在ICC组织中的阳性表达率为44.9%。Smad 4蛋白在高分化ICC中的表达率为26.1%（6/23），在低、中分化ICC中的表达率为61.5%（16/26），34.3%（12/35）和71.4%（10/14）的组织中Smad 4表达阴性ICC在病理学肿瘤淋巴结转移（pTNM）I ~ II期和pTNM III ~ IV期的差异有统计学意义（P=0.018）。72%（8/11）的淋巴结转移性ICC和73.3%（11/15）的肝内转移性ICC呈阴性表达。结论Smad 4的表达与ICC的组织学分级、临床分期及转移有关（P <0.05）。Smad 4的检测有助于判断ICC的恶性程度及预后。
Background Smad4 is found mutated in many cancers. It acts as a tumor suppressor in the regulation of TGF-8 signaling pathway. The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinonna (ICC) and its relationship with the biological behavior and prognosis of the disease.Methods Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by imnnunohistochemical methods using Smad4 monoclonal antibodies. The expression of Smad4 was compared with the clinical pathological characteristics of the patients.Results The expression of Smad4 was 100% positive in normal liver tissues, which was higher than that in the ICC (44.9%). Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5% (16/26) of poorly to moderately differentiated ICCs, and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P=0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage I-II and pTNM stage III-IV separately. Furthermore, 72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein. The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P=0.000).Conclusions The expression of Smad4 was associated with the histological grade, clinical stage, and metastasis of ICC (P < 0.05). The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.