Immunohistochemical Analysis of EZH2 and E-Cadherin Expression in Pancreatic Adenocarcinoma in Fine Needle Aspiration
Ling Gao, Tatjana Antic, Elizabeth Hyjek, Can Gong, Jeffrey Mueller, Irving Waxman, Richard DeMay, Ward Reeves. University of Chicago, Chicago, IL
Background: Pancreatic adenocarcinoma (PAC) is the fourth deadliest cancer in the US. Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has improved PAC detection by obtaining diagnostic tissue that may be the only available in the inoperable patients. Recent studies show that partial or complete loss of E-cadherin (EC) is an independent poor prognostic indicator of PAC, related to anti-VEGF drug resistance. Similarly, nuclear accumulation of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that mediates increased invasiveness and metastasis by silencing downstream targets including EC, is a hallmark of poorly differentiated PAC. Depletion of EZH2 in vitro has been shown to sensitize cancer cells to chemotherapy. The present study aims to determine EC and EZH2 status in PAC in order to provide biomarkers for prognosis and potential treatment.
Design: IHC was performed on paraffin sections of EUS-FNA cell blocks from 38 PAC cases selected from 2009-2011 Cytopathology files. GI pick-ups served as an internal control. The intensity of EZH2 and EC expression in PAC and normal GI pick-ups were scored by a four tier grading system: negative (-), weak positive (+), moderate positive (++ to +++) and strong positive (++++).
Results: In 33 PAC cases, EZH2 demonstrated variable nuclear reactivity focally or diffusely. In GI pick-ups, EZH2 showed diffuse moderate nuclear reactivity. EC demonstrated strong membranous expression in normal epithelium and partial or complete loss in the areas of PAC. The majority of cases with poorly differentiated PAC, especially single tumor cells, showed near or complete loss of EC, while the nuclear reactivity of EZH2 was focally or diffusely increased (Fig 1). However, not all single tumor cells showed strong EZH2 expression. Five PAC cases showed minimal or no EZH2 expression but decreased EC expression, and 2 showed complete loss of EC focally.
Conclusions: IHC for EZH2 and EC can be successfully performed on EUS-FNA of PAC. Our results indicate that EZH2 and EC are not always inversely expressed, and the EZH2 expression level does not always correlate with the level of tumor differentiation. Therefore, analysis of EZH2 and EC expression may be helpful in prognostic stratification and treatment decisions in PAC.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 65, Monday Morning