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Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy
Open AccessArticle

Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses Than Seen in the Eosinophilic Subtype

Histopathology Core Facility, Faculty of Medicine, Niigata University, Niigata 951-8510, Japan
Department of Pathology and Molecular Pathology, University and University Hospital Zurich, CH-8091 Zurich, Switzerland
Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan
Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland
Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
Department of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka 430-8558, Japan
Department of Pathology, Niigata Cancer Center Hospital, Niigata 951-8566, Japan
Department of Pathology, Tachikawa General Hospital, Nagaoka, Niigata 940-8621, Japan
Department of Pathology, Gifu University Hospital, Gifu 501-1194, Japan
Department of Pathology, Niigata City General Hospital, Niigata 950-1197, Japan
Department of Diagnostic Pathology, Nagaoka Red Cross Hospital, Nagaoka, Niigata 940-2085, Japan
Division of Pathology, Niigata University Medical & Dental Hospital, Niigata 951-8520, Japan
Department of Anatomic Pathology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan
Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan
Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan
Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan
Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi 780-8562, Japan
Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan
Department of Surgical Pathology, Tokyo Women’s Medical University Hospital, Shinjuku-ku, Tokyo 162-8666, Japan
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1492;
Received: 8 August 2019 / Revised: 21 September 2019 / Accepted: 26 September 2019 / Published: 3 October 2019
(This article belongs to the Special Issue Renal Cell Carcinoma)
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. View Full-Text
Keywords: chromophobe renal cell carcinoma; pale cell; eosinophilic variant; chromosomal loss; copy number analysis; renal cell carcinoma chromophobe renal cell carcinoma; pale cell; eosinophilic variant; chromosomal loss; copy number analysis; renal cell carcinoma
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Ohashi, R.; Schraml, P.; Angori, S.; Batavia, A.A.; Rupp, N.J.; Ohe, C.; Otsuki, Y.; Kawasaki, T.; Kobayashi, H.; Kobayashi, K.; Miyazaki, T.; Shibuya, H.; Usuda, H.; Umezu, H.; Fujishima, F.; Furusato, B.; Osakabe, M.; Sugai, T.; Kuroda, N.; Tsuzuki, T.; Nagashima, Y.; Ajioka, Y.; Moch, H. Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses Than Seen in the Eosinophilic Subtype. Cancers 2019, 11, 1492.

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  • Externally hosted supplementary file 1
    Doi: 10.5281/zenodo.3362283
    Description: Table S1: Copy number variation (chromosomal losses) in classic and eosinophilic chromophobe renal cell carcinomas in TCGA-KICH cohort (Chr. = chromosome) Table S2: Clinicopathological and copy number variation data of 64 chRCC of TCGA-KICH cohort.
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