A Comparison Of Twist And E-cadherin Expression In Primary Lung Cancer And Corresponding Metastases

Purpose:Development of metastasis is one of the main causes of lung cancer-related death. It has been known previously that up-regulation of Twist,a highly conserved basic helix-loop-helix transcription factor, in lung cancer cells can promote epithelial to mesenchymal transition through down-regulation of E-cadherin. The aim of this study was to determine if the Twist and E-cadherin status of primary and metastatic lung carcinoma differs and to correlate Twist and E-cadherin expression in primary and metastatic lung cancer specimens.Method:Eleven patients with lung cancer and distant metastases were retrospectively studied,of whom both the primary and metastasis lesions were resected in Provincial Hospital affiliated to Shandong University,Shandong,China, from 2000 to 2009.Immunohistochemistry Streptavidin-Peroxidase(SP)staining was used to detect the expression of Twist and E-cadherin.The sections were scored for twist expression using a four-titer scale: 0, negative;1,weak signal;2,intermediate signal;and 3, strong signal. For E-cadherin,staining intensity was scored as 0(negative),1(trace), 2 (weak),3(intermediate) and 4(strong).Extent of staining was scored according to the percentage of tumor cells with membranous E-cadherin expression in relation to the whole cancer areas(0% to 100%).Then, the scores were multiplied and divided into 4 groups (5 to 100,101 to 200, 201 to 300, and 301 to 400) as corresponding staining degrees(1,2,3, and 4).Correlation analysis between Twist and E-cadherin expression was carried out by comparing total scores for each protein expression in the same sample using Spearman rank test.Wilioxon test was used to compare the Twist and E-cadherin status between primary tumours and related metastatic sites.Result:we demonstrated an overexpression of Twist protein in lung cancer tissues and found that increased Twist expression was correlated with decreased membranous E-cadherin expression. Discordance of Twist expression was observed in two(18.2%) patients. In one case, Twist was expressed higher in the primary tumor than in the metastasis. For E-caherin,nine cases(81.8%)showed primary tumor/metastasis discordance:in nine cases,E-caherin was expressed higher in the primary tumor than in the metastasis.Conclusion:E-cadherin can re-express in metastasis and Twist expression is not stable during metastatic progression. Our data imply that Twist induces EMT on NSCLC by reducing E-caherin expression,thus promoting metastasis.