gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Nuclear LEF1/TCF4 correlate with poor prognosis in cerebral metastasis of lung adenocarcinomas

Meeting Abstract

  • Laila Siam - Abteilung für Neurochirurgie, Universitätsklinikum Göttingen
  • Annalen Bleckmann - Hämatologie/Onkologie, Universitätsklinikum Göttingen; Medizinische Statistik, Universitätsklinikum Göttingen
  • Florian Klemm - Hämatologie/Onkologie, Universitätsklinikum Göttingen
  • E. Rietkötter - Hämatologie/Onkologie, Universitätsklinikum Göttingen
  • Christiane Wegner - Neuropathologie, Universitätsklinikum Göttingen
  • Frank Kramer - Medizinische Statistik, Universitätsklinikum Göttingen
  • Tim Beissbarth - Medizinische Statistik, Universitätsklinikum Göttingen
  • Veit Rohde - Abteilung für Neurochirurgie, Universitätsklinikum Göttingen
  • Claudia Binder - Hämatologie/Onkologie, Universitätsklinikum Göttingen
  • Christine Stadelmann - Neuropathologie, Universitätsklinikum Göttingen
  • Tobias Pukrop - Abteilung für Neurochirurgie, Universitätsklinikum Göttingen

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMO.11.04

doi: 10.3205/13dgnc092, urn:nbn:de:0183-13dgnc0925

Published: May 21, 2013

© 2013 Siam et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: The transcription factors of the WNT-signaling pathway LEF1/TCF4 has been described in cerebral metastases of lung adenocarcinomas in mouse models. Their role in humans is unclear.

Method: We analyzed the WNT-signaling components LEF1, TCF4 and β-Catenin in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). In addition, we generated an AXIN2 and a LEF1/TCF4 gene signature, the latter as representative of WNT/β-Catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma.

Results: Nuclear TCF4 was positive in all adenocarcinoma samples, whereas only 36% depicted nuclear LEF1 and nuclear β-Catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p=0.01, HR=6.68), while nuclear β-Catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. It is Interesting that a high proliferation index Ki67 was also associated with shorter survival in this late-stage disease (p=0.03, HR 3.27).

To analyze the prognostic relevance in primary lung adenocarcinomas, we applied the AXIN2 and the LEF1/TCF4 gene signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p=0.01, HR=0.32). These clusters displayed diverging enrichment patterns of the cell cycle pathway.

Conclusions: In conclusion, our data show that LEF1/TCF4, but not β-Catenin, have prognostic relevance in cases of primary human lung adenocarcinomas and those with cerebral metastases. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of β-Catenin in this setting.