Assessment of HER-2 status in pancreatic adenocarcinoma: correlation of immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and survival

Am J Surg Pathol. 2005 Sep;29(9):1125-34. doi: 10.1097/01.pas.0000160979.85457.73.


HER-2 is a transmembrane growth factor receptor recognized in overexpression as an independent adverse prognostic factor in several cancers. This study measured HER-2 overexpression in pancreatic adenocarcinoma at the genetic, transcriptional, and translational level. Expression was gauged with regard to stage, grade, and survival. Pancreatic adenocarcinoma samples (n = 30) were analyzed with immunohistochemical labeling for HER-2 protein, Quantitative real-time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement of HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 gene expression. HER-2 expression in benign pancreatic lesions (n = 10) provided a control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+ immunohistochemistry (IHC) labeling, seven (23%) had significantly increased expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene amplification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance between methodologies was poor, but the best agreement was seen between FISH aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and FISH aneuploidy status (67% agreement). Tumor stage was positively associated with HER-2 mRNA and protein expression, but tumor grade and other patient characteristics did not reach statistical significance. A poor survival outcome was demonstrated with positive HER-2 status in all three measures of overexpression (Kaplan-Meier log-rank score; P < 0.01 [IHC], P = 0.05 [Q-RT-PCR], P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell surface levels highlights the limitations of immunohistochemical evaluation alone and stresses the need for further evaluation of response to anti-HER-2 targeted therapies in tumors displaying overexpression in gene copy, mRNA, and receptor protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Biomarkers, Tumor / analysis
  • Female
  • Gene Amplification
  • Gene Dosage
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • RNA, Messenger / analysis
  • Receptor, ErbB-2 / metabolism*
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Survival Rate


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptor, ErbB-2