Mp36-12 Classification by Sarcomatoid Feature Abundance in Renal Cell Carcinoma Reveals Differential Patient Outcomes and Transcriptomic Features

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance I (MP36)1 May 2024MP36-12 CLASSIFICATION BY SARCOMATOID FEATURE ABUNDANCE IN RENAL CELL CARCINOMA REVEALS DIFFERENTIAL PATIENT OUTCOMES AND TRANSCRIPTOMIC FEATURES Nicholas J. Salgia, Wilhelm A. Aubrecht, Lin Wang, Bebu Ram, Brianna J. Wasik, Adil Khan, Kristopher Attwood, Jorge Daza, Mark D. Long, Kevin H. Eng, Bo Xu, Jason B. Muhitch, and Eric C. Kauffman Nicholas J. SalgiaNicholas J. Salgia , Wilhelm A. AubrechtWilhelm A. Aubrecht , Lin WangLin Wang , Bebu RamBebu Ram , Brianna J. WasikBrianna J. Wasik , Adil KhanAdil Khan , Kristopher AttwoodKristopher Attwood , Jorge DazaJorge Daza , Mark D. LongMark D. Long , Kevin H. EngKevin H. Eng , Bo XuBo Xu , Jason B. MuhitchJason B. Muhitch , and Eric C. KauffmanEric C. Kauffman View All Author Informationhttps://doi.org/10.1097/01.JU.0001008612.93052.9d.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sarcomatoid renal cell carcinoma (sRCC) is defined by the presence of pathognomonic spindle cells. sRCC thus contains variable sarcomatoid feature amounts intermixed with epithelial carcinoma, however classification of this aggressive disease is agnostic to sarcomatoid proportion. We investigated whether sRCC classification into sarcomatoid-high vs -low groups could improve prognostic value and reveal biology underlying dedifferentiation and its clinical aggressiveness. METHODS: sRCC cases (n=104) were identified from an institutional nephrectomy patient registry. Sarcomatoid feature involvement for each tumor was annotated by a blinded genitourinary pathology team. Clinical, sociodemographic, and pathologic features were collated. Unbiased statistical stratification into high versus low sarcomatoid percentages was performed, coalescing on a cut-point of≥10% sarcomatoid features. RNA sequencing was performed on a subset (n=45) of tumors; Hallmark gene set enrichment analysis was performed, and cases were assigned into previously defined microenvironmental clusters (Motzer et al. Cancer Cell. 2020). RESULTS: Compared to sarcomatoid-low patients (n=52), sarcomatoid-high patients (n=52) experienced significantly shorter overall survival (median 14.5 vs. 62.9 months, p<0.01; Figure 1A) including in multivariable analysis, and significantly shorter metastasis-free (median 10.7 vs. 39.0 months, p=0.043) among those with localized disease at resection. Transcriptomic analyses of tumors demonstrated upregulation of 10 Hallmark pathways relating to epithelial-to-mesenchymal transition, cell cycle/proliferation, reactive oxidative species, and immune activity in sarcomatoid-high (n=24) versus sarcomatoid-low (n=21) tumors (q<0.05). Classification by microenvironmental phenotype revealed a predominance of proliferative, inflammatory, and immune effector phenotypes within sarcomatoid-high tumors whereas hypoxia/angiogenesis phenotypes were predominant in sarcomatoid-low tumors. CONCLUSIONS: These findings demonstrate prognostic value for sRCC stratification into high and low sarcomatoid abundance groups and additionally highlight key transcriptomic features underlying differences in clinical outcome. Download PPT Source of Funding: NJS is supported by NIH T32CA085183. JBM is supported by NIH CA270155, DOD KCRP HT94252310666 and DOD KCRP W81XXWH2010720. Further support for all authors by the NCI Cancer Center Support Grant P30CA016056 awarded to Roswell Park Comprehensive Cancer Center © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e596 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Nicholas J. Salgia More articles by this author Wilhelm A. Aubrecht More articles by this author Lin Wang More articles by this author Bebu Ram More articles by this author Brianna J. Wasik More articles by this author Adil Khan More articles by this author Kristopher Attwood More articles by this author Jorge Daza More articles by this author Mark D. Long More articles by this author Kevin H. Eng More articles by this author Bo Xu More articles by this author Jason B. Muhitch More articles by this author Eric C. Kauffman More articles by this author Expand All Advertisement PDF downloadLoading ...