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Comparative Study
. 2004 Mar 8;90(5):1053-8.
doi: 10.1038/sj.bjc.6601645.

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

R Grützmann  1 , J Lüttges, B Sipos, O Ammerpohl, F Dobrowolski, I Alldinger, S Kersting, D Ockert, R Koch, H Kalthoff, H K Schackert, H D Saeger, G Klöppel, C Pilarsky
Affiliations
Comparative Study

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

R Grützmann et al. Br J Cancer. .

Abstract

Gene expression profiling revealed ADAM9 to be distinctly overexpressed in pancreatic ductal adenocarcinoma (PDAC). We examined the relevance of ADAM9 expression in PDAC diagnosis and prognosis. A total of 59 infiltrating PDACs, 32 specimens from patients with chronic pancreatitis, 11 endocrine tumours and 24 acinar cell carcinomas were immunohistochemically analysed for ADAM9 expression. Staining for ADAM9 was detected in 58 out of 59 (98.3%) PDACs and in two out of 24 (8.3%) acinar cell carcinomas, but not in endocrine tumours. In the non-neoplastic pancreas, whether normal or chronically inflamed, ADAM9 was expressed in centroacinar and intralobular duct cells, but not in interlobular duct cells and their hyperplastic lesions. Pancreatic ductal adenocarcinomas showing cytoplasmic ADAM9 expression correlated with poor tumour differentiation and also with shorter overall survival than in cases showing only an apical membranous staining pattern (P=0.001). Multivariate analysis identified cytoplasmic ADAM9 expression as an independent marker of shortened survival in a set of 42 curatively (R0) resected PDAC (P<0.05, hazard ratio 2.85, 95% confidence interval: 1.21-6.71). The results show that ADAM9 expression distinguishes PDACs from other solid pancreatic tumours. In addition, cytoplasmic ADAM9 overexpression is associated with poor differentiation and shortened survival. Therefore, ADAM9 overexpression might contribute to the aggressiveness of PDACs.

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Figures

Figure 1
Figure 1
ADAM9 immunostaining in pancreatic tissues. Well-differentiated PDAC showing distinct apical ADAM9 staining at the luminal cell membrane (A); PDAC with luminal and basolateral membranous ADAM9 staining (B); poorly differentiated PDAC with basolateral membranous and focally accentuated cytoplasmic staining (arrow) (C, D); chronic pancreatitis with faint apical staining of the epithelium of a small duct (arrow) (E); normal pancreatic tissue showing staining of the luminal cell membrane of centroacinar cells and intralobular duct cells and faint granular staining of the cytoplasm of islet cells (arrow) (F).
Figure 2
Figure 2
Kaplan–Meier curves of overall survival of PDAC patients showing different ADAM9 expression patterns (cyt: cytoplasmic; lat: basolateral).
See this image and copyright information in PMC

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