Quantitation of HER2/neu expression in primary gastroesophageal adenocarcinomas using conventional light microscopy and quantitative image analysis

Arch Pathol Lab Med. 2012 Jun;136(6):610-7. doi: 10.5858/arpa.2011-0371-OA.

Abstract

Context: Human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in a proportion of gastroesophageal (GE) adenocarcinomas, and trastuzumab treatment results in significant improvement in overall survival in patients with HER2/neu-overexpressing GE tumors. Grading of HER2/neu expression in GE tumors and its clinical application is different from that of breast cancer. HER2/neu immunohistochemistry (IHC) image analysis (IA), widely used in breast cancer, has not been studied in GE tumors.

Objective: To evaluate the correlation between manual HER2/neu IHC scoring and HER2/neu IHC image analysis in GE adenocarcinomas with characterization of associated clinicopathologic features.

Design: Tumor grade, growth pattern, and stage were evaluated in 116 cases of primary GE adenocarcinoma biopsy and resection specimens. Using anti-HER2/neu antibody and the proposed HER2/neu scoring system for gastric cancer, HER2/neu IHC expression was recorded after manual scoring and automated IA interpretation.

Results: HER2/neu overexpression (IHC 3+) was detected in 19% (10 of 54) of gastric tumors, and overall correlation between manual HER2/neu IHC interpretation and IA interpretation was 78% (42 of 54). HER2/neu overexpression (IHC 3+) was detected in 26% (16 of 62) of GE junction tumors, and the overall correlation between manual HER2/neu IHC interpretation and IA interpretation was 84% (52 of 62).

Conclusions: The HER2/neu IHC scoring system for GE adenocarcinomas differs from that of breast carcinoma. Automated IA, validated for scoring of HER2/neu IHC in breast cancer, has a low correlation between HER2/neu IHC 2+ and IHC 3+ cases scored by conventional light microscopy and cannot be reliably used in the interpretation of HER2/neu IHC expression in GE adenocarcinomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • ErbB Receptors / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / metabolism*
  • Esophagogastric Junction / pathology
  • Genes, erbB-2*
  • Humans
  • Immunohistochemistry
  • Microscopy
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • ErbB Receptors
  • Receptor, ErbB-2