title: Clinicopathologic correlations of liver kinase B1, E-cadherin, and N-cadherin expression in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Juanhan
authors.initials: J
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shundong
authors.initials: S
authors.lastname: Dai
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases