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Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma

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Abstract

For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin–eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis.

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Disclosure and conflict of interest

Lilly provided funding for part of the mutation analysis, without any restrictions and honorary for advisory board meeting (Thunnissen) to “Stichting Research Fonds Pathologie” (=non-commercial pathology VU University Medical center-linked entity).

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  1. Bart Vrugt

    Present address: Institut für Klinische Pathologie, Universitäts Spital Zürich, Schmelzbergstrasse 12, 8091, Zürich, Switzerland

Authors and Affiliations

  1. Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Erik Thunnissen, Daniëlle A. M. Heideman, Katrien Grünberg & Divera Pronk

  2. Department of Pathology, Isala klinieken, Stilobadstraat 3, Overijssel, The Netherlands

    Evan Boers

  3. Department of Epidemiology and Biostatistics, VUmc, Amsterdam, The Netherlands

    Dirk J. Kuik & Birgit I Witte

  4. Department of Pathology, Laan van Londen 1800, 3317 DA, Dordrecht, The Netherlands

    Arnold Noorduin

  5. Department of Pathology, St. Antonius Ziekenhuis, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands

    Matthijs van Oosterhout & Cees Seldenrijk

  6. Department of Pathology, UMCG, Martiniziekenhuis, Van Swietenplein 1, 9700 RM, Groningen, The Netherlands

    Hannie Sietsma

  7. Department of Pulmonology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Egbert F. Smit

  8. Department of Pathology, AZM, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands

    Robertjan van Suylen

  9. Department of Pathology AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Jan von der Thusen

  10. Department of Pathology, Martiniziekenhuis, Van Swietenplein 1, 9728 NT, Groningen, The Netherlands

    Bart Vrugt

  11. Department of Pathology, Wagnerlaan 55, 6815 AD, Arnhem, The Netherlands

    Anne Wiersma

  12. Department of Pathology, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, Netherlands

    Michael den Bakker

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  1. Erik Thunnissen
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Thunnissen, E., Boers, E., Heideman, D.A.M. et al. Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma. Virchows Arch 461, 629–638 (2012). https://doi.org/10.1007/s00428-012-1324-x

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