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.
- lung cancer
- pulmonary pathology
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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.