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

Riuko Ohashi ,Naoto Kuroda ,Yoichi Ajioka ,Fumiyoshi Fujishima ,Hiroyuki Shibuya ,Takashi Kawasaki ,Toyonori Tsuzuki ,Yoshiro Otsuki ,Mitsumasa Osakabe ,Hiroshi Kobayashi ,Aashil A Batavia ,Silvia Angori ,Yoji Nagashima ,Bungo Furusato ,Chisato Ohe ,Niels J Rupp ,Hiroyuki Usuda ,Kazuhiro Kobayashi ,Tamotsu Sugai ,Tatsuhiko Miyazaki ,Peter Schraml ,Hajime Umezu ,Holger Moch

doi:10.3390/cancers11101492

Abstract

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.

Highlights

Chromophobe renal cell carcinoma is a distinct histological entity of renal cell carcinoma (RCC) described by Thoenes et al [1] in 1985. chromophobe renal cell carcinomas (chRCCs) accounts for approximately 5–7% of RCC [2,3,4].Thoenes et al used the term chromophobe cell for larger cells with reticular, but not clear cytoplasm and prominent cell membranes [1,2]
We used the absence of voluminous pale cells to define eosinophilic chRCC
More than 10 years ago, Brunelli et al analyzed classic and eosinophilic chRCCs by fluorescence in situ hybridization, but they have not observed different frequencies of chromosomal 2, 6, 10, and 17 losses [11]. This is in contrast to our OncoScan results with more chromosomal copy number variation (CNV) in classic than in eosinophilic chRCC

Summary

Introduction

Chromophobe renal cell carcinoma (chRCC) is a distinct histological entity of renal cell carcinoma (RCC) described by Thoenes et al [1] in 1985. Thoenes et al used the term chromophobe cell for larger cells with reticular, but not clear cytoplasm and prominent cell membranes (plant cell-like) [1,2]. Three years later, these authors described eosinophilic cells with smaller size and with fine oxiphilic granularity as a second cell component of chRCC [3]. Crotty et al used the term pale cell instead of the formerly used term chromophobe cell and considered pale cell and eosinophilic cell [5] as two main cell types in chRCC. Several ultrastructural studies showed that pale cells are characterized by numerous cytoplasmic microvesicles, a feature probably related to defective mitochondrial development, whereas mitochondria are abundant in eosinophilic cells [2,6,7,8].

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Conclusion