Abstract
Chromophobe renal cell carcinoma (chRCC) patients have good prognosis. Only 5%–10% patients die of metastatic disease after tumorectomy, but tumor progression cannot be predicted by histopathological parameters alone. chRCC are characterized by losses of many chromosomes, whereas gene mutations are rare. In this study, we aim at identifying genes indicating chRCC progression. A bioinformatic approach was used to correlate chromosomal loss and mRNA expression from 15287 genes from The Cancer Genome Atlas (TCGA) database. All genes in TCGA chromophobe renal cancer dataset (KICH) for which a significant correlation between chromosomal loss and mRNA expression was shown, were identified and their associations with outcome was assessed. Genome-wide DNA copy-number alterations were analyzed by Affymetrix OncoScan® CNV FFPE Microarrays in a second cohort of Swiss chRCC. In both cohorts, tumors with loss of chromosomes 2, 6, 10, 13, 17 and 21 had signs of tumor progression. There were 4654 genes located on these chromosomes, and 13 of these genes had reduced mRNA levels, which was associated with poor outcome in chRCC. Decreased CDKN1A expression at mRNA (p = 0.02) and protein levels (p = 0.02) were associated with short overall survival and were independent predictors of prognosis (p < 0.01 and <0.05 respectively). CDKN1A expression status is a prognostic biomarker independent of tumor stage. CDKN1A immunohistochemistry may be used to identify chRCC patients at greater risk of disease progression.
Highlights
Chromophobe renal cell carcinoma is the third most common histological subtype of RCC and accounts for approximately 5–7% of RCC [1,2,3]
(ISUP) grading system and the older Fuhrman grading are not recommended for Chromophobe renal cell carcinoma (chRCC) [1,8], The current 2016 World Health Organization (WHO)/International Society of Urological several studies have challenged to Fuhrman develop grading a histopathological grading grading system and the older are not recommended for system chRCC for chRCC
We demonstrated that decreased Cyclin-dependent kinase inhibitor 1A (CDKN1A) expression at the mRNA and protein levels is an independent predictor of outcome in two independent chRCC cohorts
Summary
Chromophobe renal cell carcinoma (chRCC) is the third most common histological subtype of RCC and accounts for approximately 5–7% of RCC [1,2,3]. (ISUP) grading system and the older Fuhrman grading are not recommended for chRCC [1,8], The current 2016 World Health Organization (WHO)/International Society of Urological several studies have challenged to Fuhrman develop grading a histopathological grading Pathology (ISUP). Only recently, it was [1,8], several studies have challenged to develop a histopathological grading system for reported that classic harbors a larger number of chromosomal losses than in the eosinophilic chRCC [4,6,7,9,10,11,12,13]. Only recently, it was reported classic harbors a largerby number of chromosomal than in the eosinophilic subtype [14], that which is chRCC often accompanied reduced expression losses of “CYCLOPS”
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