The Role of Notch Signaling Pathway in Human Fetal Pancreas and Pancreatic Cancer.
Huankai Hu, Lan Zhou, Amad Awadallah, Wei Xin. University Hospitals of Cleveland, Case Medical Center, OH; Case Western Reserve University, Cleveland, OH
Background: Notch signaling pathway plays an important role in the pancreatic embryogenesis mainly by animal model studies. There are limited studies of notch pathway on the development of human pancreas. Here we examine the expression of Notch1, the main notch receptor in the pancreas, in human fetal pancreas obtained from autopsy.
Currently targeting notch signaling pathway with γ-secretase inhibitor has been extensively studied as a treatment option for patients with pancreatic ductal carcinoma since notch pathway activation is an early event in the pancreatic tumorigenesis. The expression of Hes1 is one of the indicators for Notch activation. Here we compare Notch1 expression in the human pancreatic ductal adenocarcinoma and its precursors and explore the role of notch pathway in the pancreatic ductal adenocarcinoma.
Design: 43 autopsy cases of normal fetal pancreas and 66 surgical cases of pancreatic ductal adenocarcinoma were studies. Immunohistochemistry was performed using antibodies specific for Notch1 and Hes1.
Results: Notch 1 expression is identified in acinar cells and centroacinar cells, but not ductal cells or endocrine cells. The level of Notch1 expression increases during pancreatic maturation and reaches plateau right after birth. No expression of Notch1 is identified in acinar to ductal metaplasia and PanIN1-3. Notch1 reactivation is identified in 33% cases of pancreatic ductal adenocarcinoma. The notch activation in the cancer is confirmed by Hes1 expression. Notch1 expression in pancreatic ductal adenocarcinoma shows poorer differentiation comparing to Notch1 negative cancers.
|Positivity (%)||Expression Pattern|
|Normal pancreas||100||diffuse membrane|
|Chronic pancreatitis||100||variable, membrane|
|Acinar to ductal metaplasia||0||NA|
|Ductal adenocarcinoma||33||variable, luminal|