- Human pathology

Home > E. Pathology by systems > Urinary system > Kidneys > clear cell renal cell carcinoma

clear cell renal cell carcinoma

Wednesday 21 April 2004

renal clear cell carcinoma, ccRCC





- 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.


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


- 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 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)


- bilateral clear cell renal cell carcinoma


- 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


- 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