Molecular characterization and diagnostic criteria of renal cell carcinoma with emphasis on liquid biopsies

Abstract

Introduction: Over the past 6 years, important genomic and transcriptomic studies performed on RCC reported a comprehensive molecular description of RCC pathogenic alterations. Such molecular findings pave the way for an integrated classification, based on histopathology aspects and molecular alterations in order to personalize the clinical management of RCC. Areas covered: The aim of this review is to evaluate the current knowledge and the potential value of liquid biopsy in RCC. Studies on presence and analysis of circulating tumor DNA (ctDNA), circulating RNA, specific microRNA, long non-coding RNA, and circulating tumor cells are reported for each phase of disease, from the diagnostic setting to the localized disease and, lastly, in the metastatic stage. Expert opinion: Advantages of liquid biopsies compared to serial tissue sampling are numerous. However, some limitations must be addressed before considering liquid biopsy as a noninvasive biomarker of clinical utility. The suboptimal sensitivity depends on the assessment technique and genetic platforms used, the tumor organ, the tumor stage, tumor heterogeneity, and clonality. The rate of discordance with tumor tissue genotyping may depends on temporal heterogeneity, spatial heterogeneity, and/or assay error (false-negative or false-positive genotyping).