Most common histological type of renal cell carcinoma

Refer Robbins 9/e p953 Clear cell carcinoma. This is the most common type, accounting for 70% to 80% of renal cell cancers. The tumors are made up of cells with clear or granular cytoplasm and are nonpapillary. They can be familial, but in most cases (95%) are sporadic. In 98% of these tumors, whether familial, sporadic, or associated with VHL syndrome, there is loss of sequences on the sho arm of chromosome 3. The deleted region harbors the VHL gene (3p25.3). A second nondeleted allele of the VHL gene shows somatic mutations or hypermethylation-induced inactivation in up to 80% of clear cell cancers, indicating that the VHL gene acts as a tumor suppressor gene in both sporadic and familial cancers (Chapter 7). The VHL gene encodes a protein that is pa of a ubiquitin ligase complex involved in targeting other proteins for degradation. Impoant among the targets of the VHL protein is the transcription factor hypoxia- inducible factor-1 (HIF-1). When VHL is inactive, HIF-1 levels remain high, even under normoxic conditions, causing inappropriate expression of a number of genes that are turned on by HIF. These include genes that promote angiogenesis, such as VEGF, and genes that stimulate cell growth, such as insulin-like growth factor-1 (IGF-1). In addition, HIF collaborates in complex ways with the oncogenic factor MYC to "reprogram" cellular metabolism in a way that ors growth. D