1. ¹Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX, USA
2. ²Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA
3. ³Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA

Correspondence: Dr KL O'Connor, PhD, Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0525, USA. E-mail: kloconno@utmb.edu

Received 9 December 2006; Revised 5 March 2007; Accepted 7 March 2007; Published online 13 April 2007.

Abstract

Pancreatic adenocarcinomas are highly invasive cancers for reasons that are currently unclear. Here we sought to determine if the proinvasive integrin 64 may be related to pancreatic adenocarcinoma tumor progression. Expression of integrin 64 was analyzed via immunohistochemistry for the 4 subunit in normal pancreas, pancreatic intraepithelial neoplasia (PanIN) lesions, pancreatic adenocarcinomas and chronic pancreatitis. In normal pancreatic ducts, integrin 64 was noted only at the cell's basal interface with the basement membrane. In pancreatic adenocarcinomas, 92% (104/113) demonstrated overexpression of integrin 64 and altered localization to the cytoplasm and membranous regions. This pattern of expression was observed in all PanIN lesions as early as PanIN-1A, and was evident in lesions that were juxtapositioned to normal epithelium. In contrast, 93% (13/14) of chronic pancreatitis samples resembled the staining pattern of normal pancreas. When cancer was present in areas of chronic pancreatitis, this altered expression of 64 integrin identified the cancer. We conclude that integrin 64 is expressed only on the basal surface of ductal cells in normal pancreas and chronic pancreatitis. During pancreatic adenocarcinoma progression, the 64 integrin is dramatically overexpressed and displays altered localization at the earliest stages of PanIN, thus representing an early event in pancreatic adenocarcinoma progression.