1. ¹Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
2. ²Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
3. ³Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
4. ⁴Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
5. ⁵Department of Pathology, Academisch Medisch Centrum, Amsterdam, The Netherlands

Correspondence: Dr M Goggins, MD, Department of Pathology, Medicine, and Oncology, The Johns Hopkins Medical Institutions, 632 Ross Building, 720 Rutland Ave, Baltimore, MD 21205-2196, USA. E-mail: mgoggins@jhmi.edu

Received 25 May 2004; Revised 11 October 2004; Accepted 11 October 2004; Published online 25 March 2005.

Abstract

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.