title: Correlation of epithelial-mesenchymal transition markers with clinicopathologic parameters in adenocarcinomas and squamous cell carcinoma of the lung.
abstract: Epithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial cell junction proteins and the gain of mesenchymal markers. The aim of this study was to analyze the associations between the EMT-related markers vimentin, E-cadherin, β-catenin, slug, snail, and twist1 and clinicopathologic parameters as well as epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung carcinoma (NSCLC). Fifty-nine squamous cell carcinomas (SCC) and 43 adenocarcinomas (AD) were immunohistochemically examined for respective EMT markers and for EGFR, using the EGFR PharmDx kit (Dako) for protein expression and automated silver enhanced in situ hybridization (SISH) for copy number. Vimentin expression in tumor epithelia was significantly higher in AD samples than in SCC samples (P=0.015). Among AD samples, vimentin expression was positively correlated with histologic grade (2 vs. 3; P=0.021) and exhibited a tendency toward a positive correlation with pTNM stage (I vs. II-IV; P=0.052). EGFR gene copy number was positively correlated with EGFR protein expression among both AD samples (P=0.008) and SCC samples (P=0.042), with EGFR protein expression being significantly higher in SCC samples compared with AD (P=0.038). Among AD samples, EGFR protein expression was associated with higher cytoplasmic expression of β-catenin (P=0.031). Among SCC samples, EGFR protein expression was negatively correlated with nuclear expression of β-catenin (P=0.033) but positively with nuclear slug (P=0.021). The expression pattern of EMT markers in AD suggests that vimentin is a possible immunohistochemical predictor of tumor progression.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Myeong-hee
authors.initials: MH
authors.lastname: Shin
authors.forename: Chul Woung
authors.initials: CW
authors.lastname: Kim
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Kwang Sun
authors.initials: KS
authors.lastname: Suh
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin; D066246:ErbB Receptors