Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to, but distinct from, non‐sarcomatoid renal carcinomas

The Journal of Pathology: Clinical Research

Kanishka Sircar⁵  Suk-Young Yoo⁶  Tadeusz Majewski⁵  Khalida Wani⁵  Lalit R. Patel⁵  Horatiu Voicu²  Wandaliz Torres-Garcia⁶  Roel G. W. Verhaak⁶  Nizar Tannir¹  Jose A. Karam⁴  Eric Jonasch¹  Christopher G. Wood⁴  Pheroze Tamboli⁵  Keith A. Baggerly⁶  Kenneth D. Aldape³ 

[1] Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Medicine, Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA;Department of Pathology, Toronto General Hospital/Research Institute (UHN), Toronto, Ontario, Canada;Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

关键词: sarcomatoid;    renal;    carcinoma;    clear cell;    expression;    RNA‐seq;    molecular;   

DOI  :  10.1002/cjp2.23

来源: Wiley

【 摘 要 】

Abstract

Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the need to modify the pathological grading system and introduce the potential for candidate biomarkers to detect sarcomatoid change preoperatively without specifically sampling the histological sarcomatoid component.

【 授权许可】

CC BY-NC-ND   
© 2015 John Wiley and Sons Ltd and The Pathological Society of Great Britain and Ireland

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.