TY - JOUR
T1 - Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma
T2 - proposal of a novel two-tiered grading scheme
AU - Ohashi, Riuko
AU - Martignoni, Guido
AU - Hartmann, Arndt
AU - Caliò, Anna
AU - Segala, Diego
AU - Stöhr, Christine
AU - Wach, Sven
AU - Erlmeier, Franziska
AU - Weichert, Wilko
AU - Autenrieth, Michael
AU - Schraml, Peter
AU - Rupp, Niels J.
AU - Ohe, Chisato
AU - Otsuki, Yoshiro
AU - Kawasaki, Takashi
AU - Kobayashi, Hiroshi
AU - Kobayashi, Kazuhiro
AU - Miyazaki, Tatsuhiko
AU - Shibuya, Hiroyuki
AU - Usuda, Hiroyuki
AU - Umezu, Hajime
AU - Fujishima, Fumiyoshi
AU - Furusato, Bungo
AU - Osakabe, Mitsumasa
AU - Sugai, Tamotsu
AU - Kuroda, Naoto
AU - Tsuzuki, Toyonori
AU - Nagashima, Yoji
AU - Ajioka, Yoichi
AU - Moch, Holger
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Chromophobe renal cell carcinoma
KW - Kidney
KW - Mitosis
KW - Necrosis
KW - Prognosis
KW - Sarcomatoid differentiation
KW - The Cancer Genome Atlas (TCGA)
KW - Tumor grade
UR - http://www.scopus.com/inward/record.url?scp=85075385707&partnerID=8YFLogxK
U2 - 10.1007/s00428-019-02710-w
DO - 10.1007/s00428-019-02710-w
M3 - Article
C2 - 31760491
AN - SCOPUS:85075385707
SN - 0945-6317
VL - 476
SP - 409
EP - 418
JO - Virchows Archiv
JF - Virchows Archiv
IS - 3
ER -