Histochemistry and Cell Biology

, Volume 143, Issue 1, pp 1–9

Image analysis of immunohistochemistry is superior to visual scoring as shown for patient outcome of esophageal adenocarcinoma

  • Annette Feuchtinger
  • Tabitha Stiehler
  • Uta Jütting
  • Goran Marjanovic
  • Birgit Luber
  • Rupert Langer
  • Axel Walch
Original Paper

DOI: 10.1007/s00418-014-1258-2

Cite this article as:
Feuchtinger, A., Stiehler, T., Jütting, U. et al. Histochem Cell Biol (2015) 143: 1. doi:10.1007/s00418-014-1258-2

Abstract

Quantification of protein expression based on immunohistochemistry (IHC) is an important step in clinical diagnoses and translational tissue-based research. Manual scoring systems are used in order to evaluate protein expression based on staining intensities and distribution patterns. However, visual scoring remains an inherently subjective approach. The aim of our study was to explore whether digital image analysis proves to be an alternative or even superior tool to quantify expression of membrane-bound proteins. We analyzed five membrane-binding biomarkers (HER2, EGFR, pEGFR, β-catenin, and E-cadherin) and performed IHC on tumor tissue microarrays from 153 esophageal adenocarcinomas patients from a single center study. The tissue cores were scored visually applying an established routine scoring system as well as by using digital image analysis obtaining a continuous spectrum of average staining intensity. Subsequently, we compared both assessments by survival analysis as an end point. There were no significant correlations with patient survival using visual scoring of β-catenin, E-cadherin, pEGFR, or HER2. In contrast, the results for digital image analysis approach indicated that there were significant associations with disease-free survival for β-catenin, E-cadherin, pEGFR, and HER2 (P = 0.0125, P = 0.0014, P = 0.0299, and P = 0.0096, respectively). For EGFR, there was a greater association with patient survival when digital image analysis was used compared to when visual scoring was (visual: P = 0.0045, image analysis: P < 0.0001). The results of this study indicated that digital image analysis was superior to visual scoring. Digital image analysis is more sensitive and, therefore, better able to detect biological differences within the tissues with greater accuracy. This increased sensitivity improves the quality of quantification.

Keywords

Digital image analysis Esophageal adenocarcinoma Membrane-bound biomarker Immunohistochemistry HER2 EGFR pEGFR β-catenin 

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Annette Feuchtinger
    • 1
  • Tabitha Stiehler
    • 1
  • Uta Jütting
    • 2
  • Goran Marjanovic
    • 3
  • Birgit Luber
    • 4
  • Rupert Langer
    • 5
  • Axel Walch
    • 1
  1. 1.Research Unit Analytical Pathology, German Research Center for Environmental Health, Institute of PathologyHelmholtz Zentrum MünchenNeuherbergGermany
  2. 2.German Research Center for Environmental Health, Institute for Computational BiologyHelmholtz Zentrum MünchenNeuherbergGermany
  3. 3.Department of General and Visceral SurgeryAlbert Ludwigs University of FreiburgFreiburgGermany
  4. 4.Institut für Allgemeine Pathologie Und Pathologische AnatomieTechnische Universität MünchenMunichGermany
  5. 5.Institute of PathologyUniversity of BernBernSwitzerland

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