TY - JOUR
T1 - Classic chromophobe renal cell carcinoma incur a larger number of chromosomal losses than seen in the eosinophilic subtype
AU - Ohashi, Riuko
AU - Schraml, Peter
AU - Angori, Silvia
AU - Batavia, Aashil A.
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 - Funding Information:
This work was supported in part by Niigata Foundation for the Promotion of Medicine (2015 to R.O.) and the Swiss National Science Foundation grant (No. S-87701-03-01 to H.M.). The authors thank Susanne Dettwiler and Fabiola Prutek (Department of Pathology and Molecular Pathology, University Hospital Zurich), Kazue Kobayashi, Ayako Maruyama, Ayako Sato, 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. They also thank Toshio Takagi (Department of Urology, Tokyo Women?s Medical University) for insightful discussions on clinical aspects. The results published here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.
Funding Information:
Funding: This work was supported in part by Niigata Foundation for the Promotion of Medicine (2015 to R.O.) and the Swiss National Science Foundation grant (No. S-87701-03-01 to H.M.).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/10
Y1 - 2019/10
N2 - Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan® CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC.
AB - Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan® CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC.
KW - Chromophobe renal cell carcinoma
KW - Chromosomal loss
KW - Copy number analysis
KW - Eosinophilic variant
KW - Pale cell
KW - Renal cell carcinoma
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U2 - 10.3390/cancers11101492
DO - 10.3390/cancers11101492
M3 - Article
AN - SCOPUS:85074731203
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 1492
ER -
