Pdx1 Expression in Precursor Lesions and Neoplasms of the Pancreas
JY Park, SM Hong, M Goggins, A Maitra, RH Hruban. Johns Hopkins Hospital, Baltimore, MD
Background: Pdx1 is a homeobox transcription factor required for the development of both the endocrine and the exocrine pancreas. In both animal models as well as in humans, Pdx1 has previously been shown to become restricted to the islets of Langerhans in adult life. However, Pdx1 has been reported to be expressed in some pancreatic ductal adenocarcinomas. Our goal was to characterize the expression of Pdx1 in intraductal papillary mucinous neoplasms (IPMNs), pancreatic intraepithelial neoplasia (PanIN), acinar cell carcinomas (ACCs), pancreatic endocrine neoplasms (PENs), solid pseudopapillary neoplasms (SPNs), invasive ductal adenocarcinomas (IDAs) and non-dysplastic ductal epithelium.
Design: The anti-hPdx1 (clone 267712) mouse monoclonal antibody to Pdx1 (R&D Systems, Minneapolis, MN) was used to examine 12 tissue microarrays containing 655 tissue cores from 322 patients. Tissue microarrays were created from formalin-fixed paraffin-embedded tissue sections from the surgical pathology archives. The microarrays have cores representing the following tissue types: IPMN (n=88), IDA (n=69), PanIN (n=32), ACC (n=2), PEN (n=44), SPN (n=8), invasive ductal adenocarcinoma (n=70), and non-dysplastic ductal epithelium (n=74). Immunohistochemical labeling for Pdx1 was performed using standard methods, and scored for the intensity of nuclear labeling (0, 1+, 2+) as well as the distribution of positive labeling in each tissue type (0=0%, 1=1-25%, 2=26-50%, 3=51-75%, 4=76-100%). A composite score was created by multiplying the intensity and distribution scores.
Results: Pdx1 expression was seen in non-neoplastic ductal epithelium with a previously undescribed pattern of expression within the putative centroacinar cell compartment. The Pdx1 expression score was significantly higher (p<0.0001, ANOVA) in ACC (score, 4.11), non-neoplastic ductal epithelia (2.79), and PanIN (2.44), compared to PEN (1.87), IPMN (1.72), IDA (0.99), and SPN (0.40). By subgroup analysis, IPMN cases with mild dysplasia (1.43) had significantly lower (p=0.002, ANOVA) expression than non-neoplastic ducts (2.79).
Conclusions: This is the first study to demonstrate the expression of Pdx1 in non-neoplastic ductal epithelium as well as in pancreatic ductal carcinoma precursor lesions (PanIN and IPMN). The results of the present study imply that the capacity for Pdx1 expression in ductal epithelium is not lost after embryologic development. Taken together these results indicate the possibility of a larger role for Pdx1 in pancreatic tumorigenesis.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 206, Tuesday Afternoon