Gene expression profiles of pancreatic cancer and stromal desmoplasia

Gene expression studies were undertaken in normal pancreas and pancreatic a denocarcinomas to determine new candidate genes that can potentially be use d as markers of the disease. The characteristic desmoplastic stromal reacti on of pancreatic adenocarcinoma greatly hampers expression studies in this tumour type, and usually necessitates time-consuming tissue microdissection for enrichment of the tumour cell population. We show that fine needle asp iration of cancer provides a fast and efficient way of obtaining samples hi ghly enriched in tumour cells with sufficient yields of RNA. Using Atlas ca ncer cDNA arrays with 588 cancer-related genes, we describe gene expression profiles of normal pancreas, bulk pancreatic tumour tissues and pancreatic tumour aspirates containing more than 95% tumour cells. Analysis of bulk t issue specimens revealed differentially expressed genes belonging predomina ntly to the stromal component of the tumour. This contrasted with the resul ts obtained from tumour-cell enriched samples. Several genes already descri bed in pancreatic cancer (caspase 8, TIMP1, CD9, IL-13) were also different ially expressed in our study. Furthermore, we found dysregulated expression of genes not previously associated with pancreatic adenocarcinoma, such as Rac 1, GLG1, NEDD5, RPL-13a, RPS9 and members of the Wnt5A gene family. In summary, we present a panel of genes newly identified in the pathogenesis of pancreatic adenocarcinoma and demonstrate that fine needle aspirates of the tumour mass are a convenient source of material for gene expression stu dies in tumours accompanied by desmoplastic reactions.