Clear cell renal cell carcinoma
Contributors
Daynna Wolff PhD FACMG
Tumor Type
Renal Cell Carcinoma
Tumor Classification
Clear Cell RCC
This tumor type accounts for 70-75% of all renal cell carcinoma cases (citation needed).
Description
Malignant epithelial cells with clear cytoplasm and a compact-alveolar (nested) or acinar growth pattern interspersed with intricate, arborizing vasculature. A variable proportion of cells with granular eosinophilic cytoplasm may be present. Infrequently, clear cell renal cell carcinoma has a distinct tubular pattern and rarely a pseudopapillary architecture is focally present."
IHC Markers
Positive: vimentin, CD10, RCC, PAX2, PAX8, CA-IX, EMA
Negative: CK7, CD117, AMACR, E-cadherin
Genomic Gain/Loss/LOH
| Chromosome | Gain/Loss/Amp | Region |
|---|---|---|
| 1 | Loss | 1p |
| 3 | Loss | 3p (3p21, 3p25 and/or 3p13-p14) |
| 4 | Loss | 4q |
| 5 | Gain | 5q |
| 8 | Loss | 8p |
| 9 | Loss | 9p, 9q |
| 14 | Loss | 14q |
Rearrangements
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Mutations (SNV/INDEL)
From Cosmic Mutated in >20%
Mutated in 10-20%
Mutated in 5-10%
Mutated in 2-5%
PTEN, KMT2C, AKAP9, KMT2D, TERT, RANBP2, PIK3CA, ATM, ARID1A, CDKN2A, SRGAP3, SMARCA4, MLLT4, TCF12
Note that additional rare gene mutations are listed by Randall et al (2014) [1]
mtDNA
Epigenomics (methylation)
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Main Pathways Involved
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Diagnosis
Deletion of 3p (bands) or LOH for 3p
Prognosis
Loss of 14, loss of 9p, loss of 18q and highly complex genotype are associated with high risk histological features and adverse clinical outcome, also significantly associated with high risk histologic features: loss of 1p, 4p, 9q, 15q, 16q, 17p, 18p, 21q, 22q and gains of 3q, 5p, 7p, 7q, 17q [2]. Losses of 1p, 4p, 4q, 8p, 9p, 9q, 13q, 14q and 18q correlate with higher grade and/or stage of the tumors [3][4] [5][6] [7] and loss of 4, 9p and 14q have been reported as independent prognostic factors for survival in ccRCC[8][9][10][11][12]
Therapeutics
Metastatic disease: loss of 21q, 22q
Familial Forms
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Links
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References
- ↑ Randall JM et al. (2014). Molecular aberrations in clear cell renal cell carcinoma. Cancer Metastasis Rev (2014) 33:1109–1124 PMID:25365943
- ↑ Wolff et al.
- ↑ Zhang et al, Adv Bioinform, 2010
- ↑ Wilhelm et al, Cancer res 2002; Moore et al, Oncogenesis, 2012
- ↑ Arai et al, Clin Canc Res 2008
- ↑ Gunawan et al. Cancer Res 2001
- ↑ Monzon et al, Mod Path 2011
- ↑ Zhang 2010
- ↑ Monzon 2011
- ↑ Klatte 2009
- ↑ Arai 2008
- ↑ Alimov et al Int J Oncol 2004; Moch et al 1996