Liu Shuli, Miao Yuan, Fan Chuifeng, Liu Yang, Yu Juanhan, Zhang Yong, Dai Shundong, Wang Enhua
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Appl Immunohistochem Mol Morphol. 2013 Jul;21(4):334-40. doi: 10.1097/PAI.0b013e31826b128b.
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.
肝脏激酶B1（LKB1）作为一种肿瘤抑制因子，是从观察携带LKB1基因突变的黑斑息肉综合征患者胃肠道恶性肿瘤风险增加中发现的。最近在一部分肺癌中证实了LKB1基因失活，并已证明其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，尤其是预后意义，仍 largely不清楚。我们采用免疫组织化学方法，研究了LKB1、E-钙黏蛋白和N-钙黏蛋白表达与肺癌患者临床病理参数之间的相关性。对正常支气管上皮标本进行免疫组织化学分析显示，LKB1在细胞质中呈强或中度表达，E-钙黏蛋白在细胞膜上清晰表达，而N-钙黏蛋白在细胞膜和/或细胞质中无表达或仅微弱表达。相比之下，在肺癌样本中，25.7%（29/113）的病例中LKB1表达缺失或降低，同时伴有膜性E-钙黏蛋白表达缺失（25/29，P = 0.009）以及膜性和/或细胞质N-钙黏蛋白表达增加（18/29，P = 0.007）。LKB1表达缺失与组织学类型（P = 0.001）、低分化（P = 0.004）及不良预后（P < 0.001）呈正相关。此外，LKB1表达缺失与肺腺癌样本中的淋巴结转移相关（P = 0.022），并且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一个有用标志物。
