Molecular Diagnostics
British Journal of Cancer (2009) 101, 457–464. doi:10.1038/sj.bjc.6605136 www.bjcancer.com
Published online 14 July 2009
Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse
C Kahlert1,4, H Weber1,4, C Mogler2, F Bergmann2, P Schirmacher2, H G Kenngott1, U Matterne3, N Mollberg1, N N Rahbari1, U Hinz1, M Koch1, M Aigner1 and J Weitz1
- 1Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
- 2Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
- 3Institute of Occupational and Social medicine, Vo
strasse 2, 69115 Heidelberg, Germany
Correspondence: Dr med C Kahlert, E-mail: christoph.kahlert@med.uni-heidelberg.de
4These authors contributed equally to this work
Received 29 January 2009; Revised 8 May 2009; Accepted 18 May 2009; Published online 14 July 2009.
Abstract
Background:
ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported.
Methods:
In this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters.
Results:
We could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM.
Conclusions:
Our findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer.
Keywords:
ALCAM, CD166, ADAM17/TACE, pancreatic cancer, prognostic marker
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