The Over-Expression of Prion Protein Associated with Loss of SMAD4 in Pancreatic Ductal Adenocarcinoma
L Zhang, W Xin. Nanjing Gulou Hospital, Nanjing, Jiangsu, China; University Hospital Case Medical Center, Cleveland, OH; Case Western Reserve University, Cleveland, OH
Background: Normal cellular prion protein (PrP) is a glycosyl-phosphatidylinositol anchored membrane protein. In our earlier study, we have detected that the over expression of PrP in about half of pancreatic ductal adenocarcinoma. However, we did not find genomic DNA or messenger RNA level changed, as well as genetic mutation. We concluded that the regulation of PrP expression was at post-transcriptional or translational level. SMAD4 (DPC4), which plays an important role in TGF- signaling pathway, and the loss of expression has been found in 50-60% of the pancreatic ducal adenocarcinomas. In this study, we would like to explore the relationship between SMAd4 and PrP, and investigate the possible role of SMAD4 regulating PrP expression in pancreatic ductal adenocarcinomas.
Design: Sixty-seven consecutive cases of primary pancreatic ductal adenocarcinomas were selected. Forty three of these 67 carcinoma cases had regional lymph node metastasis. Immunohistochemical study was performed on tissue microarray slides using monoclonal antibodies specific for PrP and SMAD4, respectively.
Results: By immunohistochemistry, PrP expression was not detected in normal acinar, small and large non-neoplastic ductal epithelium in all cases. SMAD4 were detected in normal pancreatic tissue and pancreatitis. We found that PrP was over-expressed in 58.2% (39/67) of pancreatic carcinomas, and loss of SMAD4 was identified in 59.7% (40/67) of pancreatic carcinomas. The expression of PrP was 80.0% (32/40) in SMAD4 negative carcinomas, which was much higher than that was 25.9% (7/27) in SMAD4 positive ones (P<0.01). Nevertheless, the association of expression of PrP and loss of SMAD4 does not correlated with the tumor staging.
Table 1: The Expressions of PrP and SMAD4 in Pancreatic Ductal Adenocarcinomas
|PrP positive||PrP negative||Total|
|Sensitiveity 80%, specificity 75%, P < 0.01|
Conclusions: Our data indicate that there is a higher rate of PrP protein over-expression in pancreatic ductal adenocarcinomas with loss of SMAD4. Therefore, the loss of SMAD4 might play an important role in regulating PrP expression, and it also suggests that PrP might involve in pancreatic carcinogenesis as a component of TGF- signaling pathway.
Category: Liver & Pancreas
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 229, Wednesday Morning