Stratification of Patients with Renal Cell Carcinoma by the Abundance of Sarcomatoid Features Reveals Differences in Survival and the Underlying Pathobiology.

Autor: Salgia NJ; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA., Aubrecht WM; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Wang L; Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Ram B; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Wasik BJ; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Khan A; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Attwood K; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Daza J; Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Long MD; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Eng KH; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Xu B; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Muhitch JB; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. Electronic address: jason.muhitch@roswellpark.org., Kauffman EC; Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. Electronic address: eric.kauffman@roswellpark.org.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2024 Oct; Vol. 7 (5), pp. 973-977. Date of Electronic Publication: 2024 Mar 12.
DOI: 10.1016/j.euo.2024.02.007
Abstrakt: Sarcomatoid renal cell carcinoma (sRCC) is histologically heterogeneous, with variable sarcomatoid amounts intermixed within epithelial carcinoma. However, the current classification for this aggressive disease is homogeneous and agnostic to the sarcomatoid proportion. We investigated whether sRCC subclassification has prognostic value and can reveal the biology underlying dedifferentiation and its clinical aggressiveness. On the basis of the intratumoral abundance of sarcomatoid features, cases were classified as sarcomatoid-high (≥10% sarcomatoid features) or sarcomatoid-low (<10% sarcomatoid features) in a cohort of 104 consecutive patients with sRCC undergoing nephrectomy at a single center. In comparison to sarcomatoid-low patients (n = 52), sarcomatoid-high patients (n = 52) had significantly shorter overall survival (median 14.5 vs 62.9 mo; p < 0.001), which was confirmed on multivariable analysis, and significantly shorter median metastasis-free survival among patients with clinically localized disease (10.7 vs 39.0 mo; p = 0.043). Transcriptomic analyses of 45 sRCC tumors revealed significant upregulation of nine hallmark pathways related to cell cycle/proliferation, epithelial-to-mesenchymal transition, reactive oxidative species, and interferon-α signaling among sarcomatoid-high (n = 24) versus sarcomatoid-low (n = 21) tumors. Categorization into transcriptomic clusters revealed predominance of proliferative, inflammatory, and immune effector phenotypes among sarcomatoid-high tumors, versus a hypoxia/angiogenesis phenotype among sarcomatoid-low tumors. Overall, these findings indicate prognostic value for sRCC subclassification into high versus low sarcomatoid groups and highlight key biology underlying the differences in clinical outcomes. PATIENT SUMMARY: Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of kidney cancer. The percentage of sarcomatoid features varies among tumors, but sRCC is still defined as a single kidney cancer type. Our results show that grouping patients according to their percentage of sarcomatoid features improves prediction of whether their tumors will become metastatic or lethal, and reveal molecular differences that may be important for this disease. Future assignment of sRCC to high and low sarcomatoid groups may help in guiding research and patient management.
(Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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