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Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme

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A Correction to this article was published on 10 March 2020

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Abstract

A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5–10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff’s alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient’s age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.

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Data availability

The data set generated and/or analyzed during the current study are not publicly available due to medical confidentiality but are available from the first author or the corresponding author on reasonable request summarized form pending the approval of the institutional review board.

Change history

  • 10 March 2020

    The legends of Figs. 1 and 3 in the published original version of the above article are incorrect.

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Acknowledgments

The authors thank the following individuals: Susanne Dettwiler and Fabiola Prutek (Department of Pathology and Molecular Pathology, University Hospital Zurich), Kazue Kobayashi, Ayako Maruyama, Naoyuki Yamaguchi (Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences), Chikashi Ikegame, Kanae Takahashi, Yukie Kawaguchi and Chiaki Yokoyama (Division of Pathology, Niigata University Medical & Dental Hospital) for their outstanding technical assistance; Aashil Batavia for critical manuscript reading (Department of Pathology and Molecular Pathology, University Hospital Zurich); Takahiro Tanaka, Nobutaka Kitamura (Clinical and Translational Research Center, Niigata University Medical & Dental Hospital) and Daisuke Tokita (Clinical and Academic Research Promotion center, Tokyo Women’s Medical University) for assistance with the statistical analysis; Toshio Takagi (Department of Urology, Tokyo Women's Medical University) for insightful discussions on clinical aspects.

Funding

This work was supported in part by Niigata Foundation for the Promotion of Medicine (2015) to RO and the Swiss National Science Foundation grant to HM (No. S-87701-03-01).

Author information

Authors and Affiliations

  1. Histopathology Core Facility, Niigata University Faculty of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    Riuko Ohashi & Yoichi Ajioka

  2. Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland

    Riuko Ohashi, Peter Schraml, Niels J. Rupp & Holger Moch

  3. Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    Riuko Ohashi & Yoichi Ajioka

  4. Department of Diagnostic and Public Health, University of Verona, Piazzale Ludovico Antonio Scuro 10, 37134, Verona, Italy

    Guido Martignoni & Anna Caliò

  5. Department of Pathology, Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy

    Guido Martignoni & Diego Segala

  6. Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany

    Arndt Hartmann, Christine Stöhr & Franziska Erlmeier

  7. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Sven Wach

  8. Institute of Pathology, Technical University Munich, Trogerstrasse 18, 81675, Munich, Germany

    Franziska Erlmeier & Wilko Weichert

  9. Department of Urology, Technical University Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, Munich, Germany

    Michael Autenrieth

  10. Department of Pathology and Laboratory Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, 573-1010, Japan

    Chisato Ohe

  11. Department of Pathology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu, 430-8558, Japan

    Yoshiro Otsuki

  12. Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, 951-8566, Japan

    Takashi Kawasaki

  13. Department of Pathology, Tachikawa General Hospital, 1-24 Asahioka, Nagaoka, 940-8621, Japan

    Hiroshi Kobayashi

  14. Department of Pathology, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan

    Kazuhiro Kobayashi & Tatsuhiko Miyazaki

  15. Department of Pathology, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata, 950-1197, Japan

    Hiroyuki Shibuya

  16. Department of Diagnostic Pathology, Nagaoka Red Cross Hospital, 2-297-1 Sensyu, Nagaoka, 940-2085, Japan

    Hiroyuki Usuda

  17. Division of Pathology, Niigata University Medical & Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, 951-8520, Japan

    Hajime Umezu

  18. Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Fumiyoshi Fujishima

  19. Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan

    Bungo Furusato

  20. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan

    Bungo Furusato

  21. Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Idai-dori, Yahaba-cho, Shiwa-gun, Iwate, 028-3695, Japan

    Mitsumasa Osakabe & Tamotsu Sugai

  22. Department of Diagnostic Pathology, Kochi Red Cross Hospital, 1-4-63-11 hadaminamimachi, Kochi, Kochi, 780-8562, Japan

    Naoto Kuroda

  23. Department of Surgical Pathology, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, 480-1195, Japan

    Toyonori Tsuzuki

  24. Department of Surgical Pathology, Tokyo Women’s Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Yoji Nagashima

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  1. Riuko Ohashi
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  2. Guido Martignoni
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Contributions

RO and HM designed the research and wrote the paper. All authors acquired the data. RO, GM, AH, AC, DS, and HM analyzed and interpreted the pathological data. RO performed statistical analysis. All authors critically reviewed, edited, and approved the manuscript. RO and HM provided funding. HM supervised the study and is the guarantor of the study.

Corresponding author

Correspondence to Holger Moch.

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This study was approved by the institutional review board of each contributing institutions.

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The authors declare that they have no conflict of interest.

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The original version of this article was revised: The legends of Figures 1 and 3 in the published original version of the above article are incorrect. The original article has been corrected.

Electronic supplementary material

ESM 1

Supplementary Figure 1 pT stage (A), sarcomatoid differentiation (B) presence of necrosis (C) and presence of mitosis (D) and time to progression in the Japanese cohort (Kaplan-Meier survival analysis). Supplementary Figure 2 pT stage (A), sarcomatoid differentiation (B), presence of necrosis (C), presence of mitosis (D) and time to progression in the Italian cohort (Kaplan-Meier survival analysis). (PDF 591 kb)

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Ohashi, R., Martignoni, G., Hartmann, A. et al. Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme. Virchows Arch 476, 409–418 (2020). https://doi.org/10.1007/s00428-019-02710-w

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