Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse.
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.
Kahlert
C
C
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. christoph.kahlert@med.uni-heidelberg.de
Weber
H
H
Mogler
C
C
Bergmann
F
F
Schirmacher
P
P
Kenngott
H G
HG
Matterne
U
U
Mollberg
N
N
Rahbari
N N
NN
Hinz
U
U
Koch
M
M
Aigner
M
M
Weitz
J
J
D051722:ADAM Proteins / Q000032:analysis; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis* / Q000502:physiology; D005260:Female; D005326:Fetal Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D020410:Activated-Leukocyte Cell Adhesion Molecule
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C000606462:ADAM17 protein, human