Immunohistochemical analysis of E-cadherin and zeste homolog 2 expression in endoscopic ultrasound-guided fine-needle aspiration of pancreatic adenocarcinoma

Cancer Cytopathol. 2013 Nov;121(11):644-52. doi: 10.1002/cncy.21310. Epub 2013 May 14.

Abstract

Background: Recent studies have demonstrated that partial or complete loss of E-cadherin (EC) and nuclear accumulation of zeste homolog 2 (EZH2) are hallmarks of poorly differentiated pancreatic adenocarcinoma (PAC). Depletion of EZH2 sensitizes cancer cells to chemotherapy in vitro. The objective of this study was to determine EC and EZH2 expression by immunohistochemistry (IHC) in samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as potential biomarkers for treatment and disease prognosis.

Methods: Thirty-eight EUS-FNA samples from patients with a PAC diagnosis were analyzed by IHC for EC and EZH2 expression. Seven corresponding surgical resection specimens were included in the study. The intensity of EZH2 and EC expression in PAC and in normal gastrointestinal pick-ups (internal positive control) was scored by using a 4-tier grading system.

Results: EC demonstrated a focal, weak-to-moderate decrease in 24 PAC samples. Complete loss of EC expression was observed in the poorly differentiated areas represented by single tumor cells. The average staining intensity of EC in samples of poorly differentiated PAC was significantly lower than that of moderately differentiated PAC samples (P = .0005). EZH2 was variably positive in 31 of 38 PAC samples. The average staining intensity of EZH2 in moderately and poorly differentiated PACs did not differ significantly (P = .81).

Conclusions: EC and EZH2 expression was determined reliably by IHC on paraffin sections of EUS-FNA cell block specimens. The current results were consistent with prior reports indicating a decrease or loss of EC expression in poorly differentiated PAC. However, EZH2 expression did not always correlate inversely with EC expression and was more heterogeneous.

Keywords: E-cadherin; EZH2; adenocarcinoma; immunohistochemistry; ultrasound-guided fine-needle aspiration; zeste homolog 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins / analysis
  • Cadherins / metabolism*
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Polycomb Repressive Complex 2 / analysis
  • Polycomb Repressive Complex 2 / metabolism*

Substances

  • Cadherins
  • Neoplasm Proteins
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2

Supplementary concepts

  • Pancreatic Carcinoma