Expression of Mesothelin mRNA in Pure Pancreatic Juice From Patients With Pancreatic Carcinoma, Intraductal Papillary Mucinous Neoplasm of the Pancreas, and Chronic Pancreatitis

Abstract

In the gene expression analysis of pancreatic carcinoma (PCa) using serial analysis of gene expression (SAGE) according to Ryu et al, the tag for the mesothelin mRNA transcript was present in 7 of 8 SAGE libraries derived from PCa but not in the 2 SAGE libraries derived from normal pancreatic duct epithelial cells. Mesothelin mRNA expression was confirmed with in situ hybridization in all 4 resected primary PCa tumors and with RT-PCR in 18 of 20 PCa cell lines, whereas mesothelin protein expression was confirmed with immunohistochemistry in all 60 resected primary PCa tissues by Argani et al. We evaluated mesothelin mRNA expression in pure pancreatic juice (PPJ) obtained from patients with PCa, chronic pancreatitis (CP), and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. We evaluated mesothelin mRNA expression in the PPJ obtained from 21 patients with PCa, 22 with CP, and 11 with IPMN with reverse transcriptase PCR (RT-PCR). The PCR products were analyzed with agarose gel electrophoresis. DNase I treatment before RT-PCR and direct sequencing of the RT-PCR bands were performed for the analysis of the RT-PCR bands. Two products, of 308 and 226 bp, were obtained with RT-PCR, and the 308-bp RT-PCR product was confirmed as being that derived from the genomic DNA by direct DNA sequencing. Mesothelin mRNA expression was discovered using RT-PCR in 11 (52%) of 21 patients with PCa, 5 (45%) of 11 with IPMN, and 3 (14%) of 22 with CP. Fisher's exact test revealed significant differences between PCa and CP for mesothelin mRNA (P < 0.01). Moreover, the RT-PCR product (226 bp) of mesothelin mRNA in the PPJ samples with PCa was generally stronger than that in the PPJ samples with IPMN. Expression of mesothelin mRNA in PPJ was not strictly specific to PCa and was apt to be stronger in PCa than in IPMN. Quantitative detection of mesothelin mRNA in PPJ may have potential diagnostic implications for pancreatic tumors.