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

  • Riuko Ohashi
  • Guido Martignoni
  • Arndt Hartmann
  • Anna Caliò
  • Diego Segala
  • Christine Stöhr
  • Sven Wach
  • Franziska Erlmeier
  • Wilko Weichert
  • Michael Autenrieth
  • Peter Schraml
  • Niels J. Rupp
  • Chisato Ohe
  • Yoshiro Otsuki
  • Takashi Kawasaki
  • Hiroshi Kobayashi
  • Kazuhiro Kobayashi
  • Tatsuhiko Miyazaki
  • Hiroyuki Shibuya
  • Hiroyuki Usuda
  • Hajime Umezu
  • Fumiyoshi Fujishima
  • Bungo Furusato
  • Mitsumasa Osakabe
  • Tamotsu Sugai
  • Naoto Kuroda
  • Toyonori Tsuzuki
  • Yoji Nagashima
  • Yoichi Ajioka
  • Holger MochEmail author
Original Article
Part of the following topical collections:
  1. Quality in Pathology

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.

Keywords

Chromophobe renal cell carcinoma Kidney Mitosis Necrosis Prognosis Sarcomatoid differentiation The Cancer Genome Atlas (TCGA) Tumor grade 

Notes

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.

Author 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.

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).

Compliance with ethical standards

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

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2019_2710_MOESM1_ESM.pdf (591 kb)
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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Riuko Ohashi
    • 1
    • 2
    • 3
  • Guido Martignoni
    • 4
    • 5
  • Arndt Hartmann
    • 6
  • Anna Caliò
    • 4
  • Diego Segala
    • 5
  • Christine Stöhr
    • 6
  • Sven Wach
    • 7
  • Franziska Erlmeier
    • 6
    • 8
  • Wilko Weichert
    • 8
  • Michael Autenrieth
    • 9
  • Peter Schraml
    • 2
  • Niels J. Rupp
    • 2
  • Chisato Ohe
    • 10
  • Yoshiro Otsuki
    • 11
  • Takashi Kawasaki
    • 12
  • Hiroshi Kobayashi
    • 13
  • Kazuhiro Kobayashi
    • 14
  • Tatsuhiko Miyazaki
    • 14
  • Hiroyuki Shibuya
    • 15
  • Hiroyuki Usuda
    • 16
  • Hajime Umezu
    • 17
  • Fumiyoshi Fujishima
    • 18
  • Bungo Furusato
    • 19
    • 20
  • Mitsumasa Osakabe
    • 21
  • Tamotsu Sugai
    • 21
  • Naoto Kuroda
    • 22
  • Toyonori Tsuzuki
    • 23
  • Yoji Nagashima
    • 24
  • Yoichi Ajioka
    • 1
    • 3
  • Holger Moch
    • 2
    Email author
  1. 1.Histopathology Core FacilityNiigata University Faculty of MedicineNiigataJapan
  2. 2.Department of Pathology and Molecular PathologyUniversity and University Hospital ZurichZurichSwitzerland
  3. 3.Division of Molecular and Diagnostic PathologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  4. 4.Department of Diagnostic and Public HealthUniversity of VeronaVeronaItaly
  5. 5.Department of PathologyPederzoli HospitalPeschiera del GardaItaly
  6. 6.Institute of PathologyUniversity Hospital Erlangen, Friedrich-Alexander-University Erlangen-NürnbergErlangenGermany
  7. 7.Department of Urology and Pediatric UrologyUniversity Hospital Erlangen, Friedrich Alexander-University Erlangen-NürnbergErlangenGermany
  8. 8.Institute of PathologyTechnical University MunichMunichGermany
  9. 9.Department of UrologyTechnical University MunichMunichGermany
  10. 10.Department of Pathology and Laboratory MedicineKansai Medical UniversityHirakataJapan
  11. 11.Department of PathologySeirei Hamamatsu General HospitalHamamatsuJapan
  12. 12.Department of PathologyNiigata Cancer Center HospitalNiigataJapan
  13. 13.Department of PathologyTachikawa General HospitalNagaokaJapan
  14. 14.Department of PathologyGifu University HospitalGifuJapan
  15. 15.Department of PathologyNiigata City General HospitalNiigataJapan
  16. 16.Department of Diagnostic PathologyNagaoka Red Cross HospitalNagaokaJapan
  17. 17.Division of PathologyNiigata University Medical & Dental HospitalNiigataJapan
  18. 18.Department of Anatomic PathologyTohoku University Graduate School of MedicineSendaiJapan
  19. 19.Cancer Genomics Unit, Clinical Genomics CenterNagasaki University HospitalNagasakiJapan
  20. 20.Department of PathologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  21. 21.Department of Molecular Diagnostic Pathology, School of MedicineIwate Medical UniversityIwateJapan
  22. 22.Department of Diagnostic PathologyKochi Red Cross HospitalKochiJapan
  23. 23.Department of Surgical PathologyAichi Medical University HospitalNagakuteJapan
  24. 24.Department of Surgical PathologyTokyo Women’s Medical University HospitalTokyoJapan

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