Ralph H. Hruban

Pdx1 Expression in Pancreatic Precursor Lesions and Neoplasms

Pancreatic and duodenal homeobox (Pdx1) is a homeobox transcription factor required for the embryonic development of the pancreas. Pdx1 expression has been earlier identified in pancreatic ductal adenocarcinomas and endocrine neoplasms. This study characterizes Pdx1 protein expression in pancreatic precursor lesions and neoplasms, including pancreatic intraepithelial neoplasia (PanIN, n=32), intraductal papillary mucinous neoplasm (IPMN, n=88), mucinous cystic neoplasm (MCN, n=3), acinar cell carcinoma (ACC, n=8), pancreatic endocrine neoplasm (PEN, n=44), pancreatoblastoma (PB, n=1), solid pseudopapillary neoplasm (n=8), invasive ductal adenocarcinoma (n=67), and nondysplastic ductal epithelium. A mouse monoclonal antibody for Pdx1 was used to examine archived surgical pathology cases and tissue microarrays containing >655 tissue cores from more than 250 pancreatic specimens. Immunohistochemical labeling for Pdx1 was performed using standard methods and scored for percentage and intensity of nuclear labeling. Among non-neoplastic pancreatic tissues, Pdx1 nuclear protein was expressed in islet cells, cells of the centroacinar cell compartment, and non-neoplastic ductal epithelium. No expression of Pdx1 was seen in non-neoplastic acinar cells. Among pancreatic neoplasms, Pdx1 consistently labeled >50% of the tumor cells in 87.5% of ACC cases and 38.6% of PEN cases. Pdx1 expression was variable in invasive ductal adenocarcinoma and precursor lesions of ductal adenocarcinomas (PanIN, IPMN, and MCN). A single case of PB was examined and it showed Pdx1 in the acinar component, but no expression in squamoid nests. Solid pseudopapillary neoplasms did not express Pdx1. This study shows Pdx1 expression in precursor lesions of ductal adenocarcinomas, PEN, ACC, and a case of PB. In the immunohistochemical evaluation of neoplasms of the pancreas, Pdx1 expression is not a finding specific to PENs and ductal adenocarcinomas, but also occurs in precursor lesions (PanIN, IPMN, MCN) and other neoplasms of the pancreas.

Tumour epithelial vimentin expression and outcome of pancreatic ductal adenocarcinomas

Purpose:Tumour epithelial vimentin expression is a marker of mesenchymal differentiation and may be a useful marker of carcinomas with more aggressive behaviour. The aim of this study was to determine the extent and prognostic significance of vimentin expression in pancreatic ductal adenocarcinomas.Methods:Vimentin expression was detected by immunohistochemistry on tissue microarrays of surgically resected pancreatic ductal adenocarcinomas from 387 patients. The percentage of vimentin-immunolabelled neoplastic cells was correlated with outcome and with clinico–pathological factors using the Kaplan–Meier method and Cox multivariate survival models.Results:In all, 45% of primary pancreatic adenocarcinomas contained neoplastic cells that expressed vimentin, and in 27.5% of the cancers >10% of cells expressed vimentin. Vimentin expression was correlated with poor histological differentiation. By both uni- and multivariate survival analysis, neoplastic vimentin expression (P<0.01, HR 1.52, 95% confidence interval 1.14–2.04) was an indicator of a shorter postsurgical survival independent of other clinico–pathological variables.Conclusion:The presence of vimentin-expressing tumour epithelial cells in surgically resected pancreatic adenocarcinomas independently predicted a shorter postsurgical survival.

Expression Profiling of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is a uniquely challenging cancer. First, it is a deadly cancer. Pancreatic cancer is the fourth leading cause of cancer death in men and in women, and, despite advances in the treatment of other types of cancer, pancreatic cancer continues to have one of the highest mortality rates of any malignancy. Each year in the U.S. approx 29,000 patients are diagnosed with pancreatic cancer, and approx 29,000 will die of their disease (1). The poor prognosis for patients with pancreatic cancer is, in large part, due to the fact that almost all patients are diagnosed at an advanced stage of disease, as no known tumor markers exist that could be used to screen for pancreatic cancer at an earlier, potentially curative stage. This is a particular problem for those patients with a strong familial history of pancreatic cancer, who may have up to a 57-fold greater risk of developing pancreatic cancer in their lifetime (2,3). Second, even when a mass caused by a pancreatic cancer is identified, it can be very difficult to establish a definitive diagnosis. Deadly infiltrating adenocarcinomas of the pancreas can be so well differentiated that it can be difficult, and even at times impossible, to distinguish cancer from reactive changes histologically. Third, even when the diagnosis can be firmly established, pancreatic cancer simply does not respond to current chemotherapeutic or radiation therapies. Perhaps more than any other tumor type, a better understanding of the gene expression of pancreatic cancer is urgently needed.