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

Erik Thunnissen*, Evan Boers, Danielle A. M. Heideman, Katrien Grunberg, Dirk J. Kuik, Arnold Noorduin, Matthijs van Oosterhout, Divera Pronk, Cees Seldenrijk, Hannie Sietsma, Egbert F. Smit, Robertjan van Suylen, Jan von der Thusen, Bart Vrugt, Anne Wiersma, Birgit I. Witte, Michael den Bakker

*Corresponding author for this work

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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 (a parts per thousand yen8/11 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.

    Original languageEnglish
    Pages (from-to)629-638
    Number of pages10
    JournalVirchows Archiv
    Volume461
    Issue number6
    DOIs
    Publication statusPublished - Dec-2012

    Keywords

    • Adenocarcinoma
    • Squamous cell carcinoma
    • Lung cancer
    • Reproducibility
    • Immunohistochemistry
    • Mutation analysis
    • GROWTH-FACTOR RECEPTOR
    • BRONCHIAL BIOPSY SPECIMENS
    • TRANSCRIPTION FACTOR-I
    • KINASE DOMAIN MUTATIONS
    • OBSERVER VARIABILITY
    • ACTIVATING MUTATIONS
    • TISSUE MICROARRAY
    • CANCER PATIENTS
    • PHASE-III
    • GEFITINIB

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