Understanding Factors that Influence Prognosis and Response to Therapy in Clear Cell Renal Cell Carcinoma

Abstract

In this review, we highlight and contextualize emerging morphologic prognostic and predictive factors in renal cell carcinoma. We focus on clear cell renal cell carcinoma (ccRCC), the most common histologic subtype. Our understanding of the molecular characterization of ccRCC has dramatically improved in the last decade. Herein, we highlight how these discoveries have laid the foundation for new approaches to prognosis and therapeutic decision-making for patients with ccRCC. We explore the clinical relevance of common mutations, established gene expression signatures, intratumoral heterogeneity, sarcomatoid/rhabdoid morphology and PD-L1 expression, and discuss their impact on predicting response to therapy.

Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

“…[11][12][13] ccRCC shows high levels of intratumor heterogeneity in terms of morphological features including pure solid tumor sheets, cystic degeneration, stroma-enrichment ranging to (at least partial) papillary growth patterns. 14 Interestingly, the growth of ccRCC follows a rather expansive than invasive mode resulting in the formation of compression of adjacent renal parenchyma and formation of a pseudo-capsule at the tumor/normal adjacent tissue interface. 15 This mode of expansion presumably translates into increased mechanical forces on growing tumor nodules and requires specialized as well as adaptive membrane composition in respective ccRCC cell populations.…”