clear cell renal cell carcinoma

Images

 https://twitter.com/dozing_dog/status/737155200624918528

Immunochemistry

 vimentin+
 CD10+ (MME)
 CK7-

Differential diagnosis

 papillary clear cell renal cell carcinoma
 juvenile-type clear cell renal cell carcinoma (juvenile renal cell carcinoma)

• TFE3-associated renal cell tumor
• TFEB-associated renal cell tumor

Molecular biology

 3p25-26: VHL locus
 3p12-p21 locus (10897333)

Renal cell carcinoma of the clear cell type (ccRCC) is associated with loss of functional von Hippel-Lindau (VHL) protein and high, homogeneous expression of the G250MN protein, an isoenzyme of the carbonic anhydrase family. High expression of G250MN is found in all ccRCCs, but not in most normal tissues, including normal human kidney.

Predisposition

 von Hippel-Lindau syndrome
 familial non-syndromic clear cell renal cell carcinoma (FNSCCRCC)

LOH

 3p LOH
 14q LOH
 18 LOH (19%)

• 18q21 LOH

Gene mutations

Sporadic clear cell renal cell carcinoma (ccRCC), the most common type of adult kidney cancer, is often associated with genomic copy number aberrations on chromosomes 3p and 5q.

Aberrations on chromosome 3p are associated with inactivation of the tumor suppressor gene von-Hippel Lindau (VHL), which activates the hypoxia-inducible factors HIF1α and HIF2α. In contrast, ccRCC genes on chromosome 5q remain to be defined.

Two VHL-deficient subtypes of ccRCC have been defined, which express both HIF1α and HIF2α (H1H2) or only HIF2α (H2).

An analysis revealed a distinct pattern of genomic aberrations in each group, with the H1H2 group displaying, on average, a more aberrant genome than the H2 group. These study provided a significant advance in understanding ccRCCs by offering a molecular definition of two subtypes with distinct characteristics as well as two potential chromosome 5q oncogenes, the overexpression of which is sufficient to promote tumorigenesis by limiting cell death.

 VHL mutations

 Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. (22138691)

miRNAs

miRNAs are small, nonprotein coding RNAs that are differentially expressed in many malignancies. 80 miRNAs are dysregulated in clear cell renal cell carcinoma. (20022054)

A significant number of dysregulated proteins in clear cell renal cell carcinoma are potential miRNA targets. Also, many clear cell renal cell carcinoma dysregulated miRNAs are phylogenetically conserved. (20022054)

Variants

 bilateral clear cell renal cell carcinoma

Physiopathology

 Both mTOR and hypoxia-induced pathways are activated in primary and metastatic ccRCC. (21881486)
 PTEN loss seems to be an early event during tumorigenesis. (21881486)
 Tumor size, HIF-1α, and phos-S6 expression are found to be independent predictors of both DSS and tumor progression in primary ccRCC. (21881486)

See also

 Tumors

• renal tumors
• Carcinomas

References

 Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Guo G, Gui Y, Gao S, Tang A, Hu X, Huang Y, Jia W, Li Z, He M, Sun L, Song P, Sun X, Zhao X, Yang S, Liang C, Wan S, Zhou F, Chen C, Zhu J, Li X, Jian M, Zhou L, Ye R, Huang P, Chen J, Jiang T, Liu X, Wang Y, Zou J, Jiang Z, Wu R, Wu S, Fan F, Zhang Z, Liu L, Yang R, Liu X, Wu H, Yin W, Zhao X, Liu Y, Peng H, Jiang B, Feng Q, Li C, Xie J, Lu J, Kristiansen K, Li Y, Zhang X, Li S, Wang J, Yang H, Cai Z, Wang J. Nat Genet. 2011 Dec 4;44(1):17-9. PMID: 22138691

 Integrative Genomic Analyses of Sporadic Clear Cell Renal Cell Carcinoma Define Disease Subtypes and Potential New Therapeutic Targets. Dondeti VR, Wubbenhorst B, Lal P, Gordan JD, D’Andrea K, Attiyeh EF, Simon MC, Nathanson KL. Cancer Res. 2011 Dec 21. PMID: 22094876

 Immunoexpression Status and Prognostic Value of mTOR and Hypoxia-Induced Pathway Members in Primary and Metastatic Clear Cell Renal Cell Carcinomas. Schultz L, Chaux A, Albadine R, Hicks J, Kim JJ, De Marzo AM, Allaf ME, Carducci MA, Rodriguez R, Hammers HJ, Argani P, Reuter VE, Netto GJ. Am J Surg Pathol. 2011 Aug 29. PMID: 21881486

 The miR-17-92 Cluster is Over Expressed in and Has an Oncogenic Effect on Renal Cell Carcinoma. Chow TF, Mankaruos M, Scorilas A, Youssef Y, Girgis A, Mossad S, Metias S, Rofael Y, Honey RJ, Stewart R, Pace KT, Yousef GM. J Urol. 2009 Dec 16. PMID: 20022054

 Bonne AC, Bodmer D, Schoenmakers EF, van Ravenswaaij CM, Hoogerbrugge N, van Kessel AG. Chromosome 3 translocations and familial renal cell cancer. Curr Mol Med. 2004 Dec;4(8):849-54. PMID: 15579032

 Woodward ER. Familial non-syndromic clear cell renal cell carcinoma. Curr Mol Med. 2004 Dec;4(8):843-8. PMID: 15579031

 Hirsch MS, Weinstein MH, Thomas A, Dal Cin P. Identical karyotypes in synchronous bilateral clear cell renal cell carcinomas. Cancer Genet Cytogenet. 2002 Nov;139(1):86-7. PMID: 12547168