Prognostic value and reproducibility of different microscopic characteristics in the WHO grading systems for pTa and pT1
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RESEARCH
Open Access
Prognostic value and reproducibility of different microscopic characteristics in the WHO grading systems for pTa and pT1 urinary bladder urothelial carcinomas Vebjørn Kvikstad1,2*† , Ok Målfrid Mangrud3†, Einar Gudlaugsson1, Ingvild Dalen4, Hans Espeland5, Jan P. A. Baak1,6,7† and Emiel A. M. Janssen1,2†
Abstract Background: European treatment guidelines for pTa and pT1 urinary bladder urothelial carcinoma depend highly on stage and WHO-grade. Both the WHO73 and the WHO04 grading systems show some intra- and interobserver variability. The current pilot study investigates which histopathological features are especially sensitive for this undesired lack of reproducibility and the influence on prognostic value. Methods: Thirty-eight cases of primary non-muscle invasive urothelial carcinomas, including thirteen cases with stage progression, were reviewed by three pathologists. Thirteen microscopic features were extracted from pathology textbooks and evaluated separately. Reproducibility was measured using Gwet’s agreement coefficients. Prognostic ability regarding progression was estimated by the area under curve (AUC) of the receiver operating characteristics (ROC) function. Results: The best reproducible features (Gwet’s agreement coefficient above 0.60) were papillary architecture, nuclear polarity, cellular maturation, nuclear enlargement and giant nuclei. Nucleoli was the strongest prognostic feature, and the only feature with an AUC above 0.70 for both grading systems, but reproducibility was not among the strongest. Nuclear polarity also had prognostic value with an AUC of 0.70 and 0.67 for the WHO73 and WHO04, respectively. The other features did not have significant prognostic value. Conclusions: The reproducibility of the histopathological features of the different WHO grading systems varied considerably. Of all the features evaluated, only nuclear polarity was both prognostic and significantly reproducible. Further validation studies are needed on these features to improve grading of urothelial carcinomas. Keywords: Papillary urothelial carcinoma, Grading, Reproducibility, Prognosis
Background Bladder cancer is the ninth most frequently diagnosed cancer worldwide. The incidence is highest in developed countries, and is the fourth most common cancer among men in Norway [1, 2]. Urothelial carcinoma accounts for about 90% of bladder cancers in industrialized countries * Correspondence: [email protected] † Jan P. A. Baak and Emiel A.M. Janssen are Both senior authors contributed equally. 1 Department of Pathology, Stavanger University Hospital, Stavanger, Norway 2 Department of Mathematics and Natural Science, University of Stavanger, Stavanger, Norway Full list of author information is available at the end of the article
[3], and 70–80% of these are non-muscle-invasive bladder cancers (NMIBC), pTa, pT1 or pTis, on first diagnosis. Among these 50–70% will recur, while only 15–25% will progress to a higher stage [4]. The follow-up of these patients is labor-intensive [5, 6], causin
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