Differentiation of Pancreatic Intraepithelial Neoplasia-3 (PanIN-3) and Ductal Adenocarcinoma of the Pancreas from Lower Grade PanINs Utilizing Immunohistochemistry for Cell Polarity Protein Lethal Giant Larva 2 (lgl2)
M Lisovsky, K Dresser, B Woda, M Mino-Kenudson. Massachusetts General Hospital, Boston; UMassMemorial Medical Center, Worcester
Background: Pancreatic intraepithelial neoplasia (PanIN) is a precursor of ductal adenocarcinoma of the pancreas (PDAC). PanIN-3 has the highest potential to progress to PDAC and its distinction from lower grade PanINs, such as PanIN-1 and PanIN-2, is important for clinical management. However, morphologic grading of PanIN suffers from significant interobserver variability and may be difficult. A product of cell polarity gene lgl2 is a marker of gastric foveolar epithelium, which is expressed in a basolateral fashion, and is lost or mislocalized in gastric epithelial dysplasia and adenocarcinoma. Since PanIN shows gastric differentiation phenotype, we investigated the utility of Lgl2 expression for differentiating PanIN-3 from lower-grade PanINs.
Design: The immunohistochemical patterns of Lgl2 expression were examined in normal pancreatic ducts, 48 PanIN lesions of all histologic grades, and 91 PDACs on a tissue microarray or conventional sections. The expression pattern was recorded as basolateral, cytoplasmic, negative, or combinations of any of them.
Results: While normal duct epithelia showed negative Lgl2 immunoreactivity, all but one of 33 lesions of low-grade PanIN showed basolateral Lgl2 staining. Conversely, all 14 lesions of PanIN-3 and all 91 PDACs showed loss of Lgl2 staining or its abnormal cytoplasmic localization. Interestingly, a basolateral expression was focally seen in 4 PDACs with a foamy gland pattern, and was always admixed with negatively stained areas.
Conclusions: Our results show that low-grade PanINs express Lgl2 in a basolateral fashion recapitulating expression in benign gastric epithelium. Loss or abnormal Lgl2 expression is seen in PanIN-3 and PDAC and could be useful in separating them from lower-grade PanINs.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 207, Tuesday Afternoon