Virchows Archiv

, Volume 455, Issue 4, pp 375–381 | Cite as

Intra- and interobserver reproducibility of interpretation of immunohistochemical stains of prostate cancer

  • Sara Jonmarker Jaraj
  • Philippe Camparo
  • Helen Boyle
  • François Germain
  • Bo Nilsson
  • Fredrik Petersson
  • Lars EgevadEmail author
Original Article


The evaluation of immunohistochemistry (IHC) is usually semiquantitative, and thus subject to observer variability. We analyzed the reproducibility of different IHC measures. Fifty TMA cores of prostate cancer were stained for PDX-1, a transcription factor overexpressed in the cytoplasm of prostate cancer cells. The strongest intensity was scored 0–3 and 1–3 was used for extent (1–33%, 34–66%, and 67–100%). The stains were evaluated twice by four observers: two genitourinary pathologists, and two medical doctors with no formal pathology training. Staining intensity was also measured with automated image analysis. The pathologists read the slides faster than nonpathologists (total time 88 and 178 min, respectively, p = 0.03). Mean weighted kappa for intraobserver agreement was 0.85 (range 0.81–0.89) for intensity and 0.43 (range 0.38–0.51) for extent with similar results among pathologists and nonpathologists. Mean weighted kappa for interobserver agreement was 0.80 (range 0.77–0.84) for intensity and 0.21 (range 0.11–0.26) for extent. The subjective estimations of intensity correlated with results of image analysis (r = 0.61–0.66, p < 0.001), but the correlation between observers was stronger (r = 0.75–0.81) and correlated better with Gleason grade. Thus, subjective assessment of intensity can be done with a high level of reproducibility while estimation of staining extent is less reliable. Although educated pathologists were faster, the level of pathology training is not crucial for obtaining reproducible results in the analysis of TMA-based studies.


Adenocarcinoma of the prostate Immunohistochemistry Reproducibility Image analysis Tissue microarray 


Conflict of interest statement

We declare that we have no conflict of interest. The Noesis company has let us use the Noesis digital analysis system free of charge, however, it has not been possible for the company to influence the results of this study


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sara Jonmarker Jaraj
    • 1
  • Philippe Camparo
    • 2
  • Helen Boyle
    • 3
  • François Germain
    • 4
  • Bo Nilsson
    • 1
  • Fredrik Petersson
    • 1
  • Lars Egevad
    • 1
    • 5
    Email author
  1. 1.Department of Oncology-Pathology, Karolinska InstitutetKarolinska University Hospital SolnaStockholmSweden
  2. 2.Service d’Anatomie et Cytologie PathologiquesHopital FochParisFrance
  3. 3.Department of OncologyCentre Leon BerardLyonFrance
  4. 4.NoesisGif sur YvetteFrance
  5. 5.International Agency for Research on CancerLyonFrance

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