Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Aug 4;101(3):457-64.
doi: 10.1038/sj.bjc.6605136. Epub 2009 Jul 14.

Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse

C Kahlert  1 , H Weber, C Mogler, F Bergmann, P Schirmacher, H G Kenngott, U Matterne, N Mollberg, N N Rahbari, U Hinz, M Koch, M Aigner, J Weitz
Affiliations

Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse

C Kahlert et al. Br J Cancer. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
CD166 expression in pancreatic cancer and normal pancreatic tissue. (A) Pancreatic tumour cells displaying a CD166 intensity of 0 next to remnant pancreatic islet cells with an intensity of 3. (B) Pancreatic tumour cells displaying a CD166 intensity of 1 next to a nerve with a CD166 intensity of 2 and remnant pancreatic islet cells with an intensity of 3. (C) Pancreatic tumour cells displaying a CD166 intensity of 2. (D) Pancreatic tumour cells displaying a CD166 intensity of 3 next to remnant pancreatic islet cells with an intensity of 3. (E) Pancreatic tumour cells displaying membranous expression of CD166. (F) Normal pancreatic tissue with membranous staining. Original magnification, × 400.
Figure 2
Figure 2
ADAM17 expression in pancreatic cancer. (A) Pancreatic tumour cells displaying an ADAM17 intensity of 0. (B) Pancreatic tumour cells displaying an ADAM17 intensity of 1. (C) Pancreatic tumour cells displaying an ADAM17 intensity of 2. (D) Pancreatic tumour cells displaying an ADAM17 intensity of 3. Original magnification, × 400.
Figure 3
Figure 3
Univariate analysis (log-rank test, Kaplan–Meier curves) of prognostic parameters in pancreatic cancer. (A) Intensity of cytoplasmic expression of CD166 (P=0.0006), (B) Membranous vs non-membranous expression of CD166 (P=0.03), (C) Intensity of cytoplasmic expression of ADAM17 (P=0.09), (D) Nodal status (P=0.02), (E) AJCC tumour stage (P=0.007), (F) adjuvant chemotherapy received vs not received (P=0.0001).
See this image and copyright information in PMC

References

    1. Arribas J, Bech-Serra JJ, Santiago-Josefat B (2006) ADAMs, cell migration and cancer. Cancer Metastasis Rev 25: 57–68 - PubMed
    1. Bech-Serra JJ, Santiago-Josefat B, Esselens C, Saftig P, Baselga J, Arribas J, Canals F (2006) Proteomic identification of desmoglein 2 and activated leukocyte cell adhesion molecule as substrates of ADAM17 and ADAM10 by difference gel electrophoresis. Mol Cell Biol 26: 5086–5095 - PMC - PubMed
    1. Burkhardt M, Mayordomo E, Winzer KJ, Fritzsche F, Gansukh T, Pahl S, Weichert W, Denkert C, Guski H, Dietel M, Kristiansen G (2006) Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer. J Clin Pathol 59: 403–409 - PMC - PubMed
    1. Choi S, Kobayashi M, Wang J, Habelhah H, Okada F, Hamada J, Moriuchi T, Totsuka Y, Hosokawa M (2000) Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin. Clin Exp Metastasis 18: 45–50 - PubMed
    1. Delcore R, Rodriguez FJ, Forster J, Hermreck AS, Thomas JH (1996) Significance of lymph node metastases in patients with pancreatic cancer undergoing curative resection. Am J Surg 172: 463–468; discussion 468–9 - PubMed

MeSH terms