title: Expression of snail, twist, and Zeb1 in malignant mesothelioma.
abstract: We examined 56 malignant mesotheliomas, 117 lung adenocarcinomas, and 34 metastatic lung adenocarcinomas with antibodies to transcription factors involved in epitheliomesenchymal transition. The tumors were stained immunohistochemically with antibodies zeb1, twist, and snail. Malignant mesotheliomas exhibited a stronger expression of zeb1 and twist than lung adenocarcinomas (p < 0.001 for both). Metastatic adenocarcinomas displayed a more frequent expression of zeb1 and twist (p < 0.001 for both) than lung adenocarcinomas. Patients with snail positive mesotheliomas experienced a better survival (p = 0.046), whereas in lung adenocarcinomas, this trait predicted worse survival (p = 0.024). Biphasic mesotheliomas had a more frequent expression of snail or zeb1 than epithelioid and sarcomatoid mesotheliomas as a group (p = 0.034 and p = 0.005, respectively). E-cadherin was more commonly present in epithelioid mesotheliomas (p = 0.002). Cases with snail positivity showed a significantly lower apoptotic index (p = 0.039). Malignant mesotheliomas display strong twist and zeb1 expression, which may be an indication of transdifferentiation between the epithelioid and sarcomatoid cell types with biphasic mesotheliomas representing tumors in active transition. Metastatic adenocarcinomas show a higher expression of zeb1 and twist than primary lung tumors, confirming our previous findings and highlighting their significance in the metastatic process. Snail expression is associated with poor prognosis in lung adenocarcinomas, but an opposite effect was seen in mesothelioma, a fact which may be related to the different cellular origin of epithelial and mesothelial cells.
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Finland.
authors.forename: Heta
authors.initials: H
authors.lastname: Merikallio
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.forename: Kaisa
authors.initials: K
authors.lastname: Salmenkivi
authors.forename: Vuokko
authors.initials: V
authors.lastname: Kinnula
authors.forename: Teihu
authors.initials: T
authors.lastname: Harju
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D012189:Retrospective Studies; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D051879:Twist-Related Protein 1 / Q000096:biosynthesis*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1