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Zeb1 and twist are more commonly expressed in metastatic than primary lung tumours and show inverse associations with claudins
  1. Heta Merikallio1,
  2. Riitta Kaarteenaho1,2,
  3. Paavo Pääkkö3,
  4. Siri Lehtonen4,
  5. Pasi Hirvikoski3,
  6. Riitta Mäkitaro1,
  7. Terttu Harju1,2,
  8. Ylermi Soini5
  1. 1Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland
  2. 2Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland
  3. 3Department of Pathology, Oulu University Hospital, Oulu, Finland
  4. 4Department of Surgery, Oulu University Hospital, University of Oulu and Clinical Research Center, Oulu, Finland
  5. 5Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University Kuopio, Kuopio, Finland
  1. Correspondence to Ylermi Soini, Department of Pathology and Forensic Medicine, School of Medicine, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; ylermi.soini{at}uef.fi

Abstract

Background Zeb1 and twist regulate expression of genes which take part in epitheliomesenchymal transition (EMT). Claudins are tight junctional proteins regulating polarity and paracellular permeability of epithelial cells.

Aims and methods To study Zeb1 and twist in 289 primary and 54 metastatic lung tumours and their relation to expression of claudins 1–5 and 7 by immunohistochemistry.

Results Metastatic tumours showed a significantly lower expression of zeb1 and twist (33.0% and 38.0% vs 5.0% and 14.5%, p<0.001 for both) and they also had a significantly lower expression of claudin 1 (p<0.001), claudin 4 (p<0.001), claudin 5 (p=0.001) and claudin 7 (p<0.001) than did primary tumours. Primary lung tumours showed a strong inverse association between zeb1 and claudin 1 (p=0.024) and claudin 2 (p=0.003). For twist an inverse association was found with claudin 5 (p=0.007). In metastatic tumours zeb1 was inversely associated with claudin 7 (p=0.050) and twist with claudin 5 (p=0.025). Overexpression of claudin 5 was associated with decreased survival (p=0.017). For zeb1 or twist, no association with survival was observed in primary or metastatic tumours.

Conclusions According to protein expression, involvement of zeb1 and twist in EMT in primary lung tumours is relatively infrequent. Carcinomas metastatic to the lung showed a significantly higher expression of these transcriptional factors than primary lung tumours, indicating their probable importance in the metastatic process. Zeb1 and twist were inversely associated with several claudins, indicating a role in their down-regulation.

  • Immunohistochemistry
  • lung cancer
  • metastasis
  • pulmonary pathology

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Footnotes

  • Funding This study was supported by Finnish Cancer Foundation, Special Government Funding (EVO) of Kuopio and Oulu University Hospital and the Finnish Lung Health Association (Filha).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the The ethics comittee of the Ostrobotnian District, Finland.

  • Provenance and peer review Not commissioned; not externally peer reviewed.

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