Clinicopathologic Correlations of Liver Kinase B1, E-Cadherin, and N-Cadherin Expression in Non-Small Cell Lung Cancer
Clinicopathologic Correlations of Liver Kinase B1, E-Cadherin, and N-Cadherin Expression in Non-Small Cell Lung Cancer
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非小细胞肺癌中肝激酶 B1、E-钙粘蛋白和 N-钙粘蛋白表达的临床病理相关性。
DOI：
10.1097/pai.0b013e31826b128b
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发表时间：
2013-07-01
影响因子：
1.6
通讯作者：
Wang, Enhua
中科院分区：
文献类型：
--
作者：
Liu, Shuli;Miao, Yuan;Wang, Enhua
肝激酶B1 （LKB1）作为肿瘤抑制因子的作用已经从观察到携带LKB1基因突变的Peutz-Jeghers综合征患者胃肠道恶性肿瘤的风险增加中出现。LKB1基因失活最近在肺癌的一个亚群中得到证实，并已被证明可触发肺腺癌细胞的上皮-间质转化。然而，LKB1蛋白表达的临床病理意义，特别是预后仍不清楚。采用免疫组化方法，研究肺癌患者LKB1、E-cadherin、N-cadherin表达与临床病理参数的相关性。正常支气管上皮细胞免疫组化结果显示，LKB1在细胞质中有强烈或中等表达，E-cadherin在细胞膜上有明显表达，而N-cadherin在细胞膜和/或细胞质上不存在或仅弱表达。相比之下，在肺癌样本中，25.7%（29/113）的病例LKB1表达缺失或降低，同时膜性E-cadherin表达缺失（25/29,P = 0.009），膜性和/或细胞质N-cadherin表达升高（18/29,P = 0.007）。LKB1表达缺失与组织学类型（P= 0.001）、分化不良（P= 0.004）、预后不良（P < 0.001）呈正相关。LKB1表达缺失与肺腺癌淋巴结转移相关（P= 0.022），是影响肺腺癌患者预后的独立因素（P= 0.003）。因此，LKB1表达缺失与上皮-间质转化标志物相关，可能是肺腺癌患者生存不良的有用标志物。
The role of liver kinase B1 (LKB1) as a tumor suppressor has emerged from the observation of increased risk of malignancy in gastrointestinal tract in Peutz-Jeghers syndrome patients harboring LKB1 gene mutations. LKB1 gene inactivation has recently been demonstrated in a subset of lung carcinoma and has been proven to trigger epithelial-mesenchymal transition in lung adenocarcinoma cells. However, the clinicopathologic significance, particularly prognosis, of LKB1 protein expression remains largely unclear. Using immunohistochemistry, we investigated the correlations between LKB1, E-cadherin, and N-cadherin expression and clinicopathologic parameters of lung cancer patients. Immunohistochemistry on specimens of the normal bronchial epithelium revealed that LKB1 was strongly or moderately expressed in the cytoplasm, and E-cadherin was expressed clearly on the cell membrane, whereas N-cadherin was absent or only weakly expressed at the membrane and/or in the cytoplasm. In contrast, in lung cancer samples, LKB1 expression was absent or decreased in 25.7% (29/113) cases accompanied with loss of membranous E-cadherin expression (25/29, P = 0.009) and increased membranous and/or cytoplasmic N-cadherin expression (18/29, P = 0.007). Loss of LKB1 expression positively correlated with histologic type (P = 0.001), poor differentiation (P= 0.004), and adverse prognosis (P < 0.001). Moreover, loss of LKB1 expression correlated with lymph node metastasis (P = 0.022) in lung adenocarcinoma samples and was an independent factor that impacted lung adenocarcinoma patients' prognosis (P= 0.003). Therefore, loss of LKB1 expression correlates with epithelial-mesenchymal transition markers and may be a useful marker of poor survival for the patient with lung adenocarcinoma.