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Expression of snail, twist, and Zeb1 in malignant mesothelioma

Authors

  • Heta Merikallio,

    1. Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland
    2. Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland
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  • Paavo Pääkkö,

    1. Department of Pathology, Oulu University Hospital, Oulu, Finland
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  • Kaisa Salmenkivi,

    1. Department of Pathology, University of Helsinki, Helsinki, Finland
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  • Vuokko Kinnula,

    1. Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
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  • Teihu Harju,

    1. Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland
    2. Department of Pathology, Oulu University Hospital, Oulu, Finland
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  • Ylermi Soini

    Corresponding author
    1. Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland
    • Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland
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Ylermi Soini, Department of Pathology and Forensic Medicine, School of Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Po Box 1627, Kuopio FI-70211, Finland. e-mail: ylermi.soini@uef.fi

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.

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