Grützmann R, Lüttges J, Sipos B, Ammerpohl O, Dobrowolski F, Alldinger I, Kersting S, Ockert D, Koch R, Kalthoff H, Schackert H K, Saeger H D, Klöppel G, Pilarsky C
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, Dresden 01307, Germany.
Br J Cancer. 2004 Mar 8;90(5):1053-8. doi: 10.1038/sj.bjc.6601645.
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.
基因表达谱分析显示，ADAM9在胰腺导管腺癌（PDAC）中明显过表达。我们研究了ADAM9表达与PDAC诊断及预后的相关性。对59例浸润性PDAC、32例慢性胰腺炎患者的标本、11例内分泌肿瘤及24例腺泡细胞癌进行免疫组织化学分析，检测ADAM9的表达情况。在59例PDAC中有58例（98.3%）检测到ADAM9染色阳性，在24例腺泡细胞癌中有2例（8.3%）检测到阳性，而在内分泌肿瘤中未检测到阳性。在非肿瘤性胰腺组织中，无论是正常的还是慢性炎症的，ADAM9均表达于中央腺泡和小叶内导管细胞，但在小叶间导管细胞及其增生性病变中不表达。与仅表现为顶端膜染色模式的病例相比，显示细胞质ADAM9表达的胰腺导管腺癌与肿瘤低分化相关，且总生存期更短（P=0.001）。多变量分析确定，在一组42例接受根治性（R0）切除的PDAC中，细胞质ADAM9表达是生存期缩短的独立标志物（P<0.05，风险比2.85，95%置信区间：1.21-6.71）。结果表明，ADAM9表达可将PDAC与其他实性胰腺肿瘤区分开来。此外，细胞质ADAM9过表达与低分化及生存期缩短相关。因此，ADAM9过表达可能促使PDAC具有侵袭性。
