Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell Carcinoma

Klatte, Tobias; Rao, Priya; Martino, Michela de; LaRochelle, Jeffrey C.; Shuch, Brian; Zomorodian, Nazy; Said, Jonathan; Kabbinavar, Fairooz; Belldegrun, Arie S.; Pantuck, Allan J.

doi:10.1200/jco.2007.15.8345

Cited by 184 publications

(199 citation statements)

References 43 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…For example, recent studies of clearcell RCC using these methodologies have had a rate of 3p loss detection ranging from 60 to 76% of the cases evaluated. 22,23 In our series, 3p losses-including the region of the VHL gene-and 5q gains were the most frequent chromosomal copy number change detected in clear-cell RCC. Losses of 3p were seen in 7/11 (64%) of clear-cell RCCs, whereas 5q gains were observed in 5/11 (45%).…”

Section: Aberrationmentioning

confidence: 57%

“…In addition, chromosomal copy number changes were evaluated in clear-cell papillary RCC using single-nucleotide polymorphism (SNP) arrays to examine genomewide changes and exclude the presence of recurrent copy number changes-such as losses of 3p and/or 5q gains-that are known to occur in clear-cell RCC. 16,[22][23][24] Quantitative real-time PCR (qRT-PCR) was carried out to evaluate VHL mRNA expression in clear-cell papillary RCC. Finally, we performed immunohistochemistry for markers of HIF pathway activation (CA9, HIF-1a, and GLUT-1) and additional markers (CK7, AMACR, TFE3, CD10, and 34bE12) shown to be relevant in the diagnosis/ differential diagnosis of these tumors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

et al. 2011

View full text Add to dashboard Cite

Over the past few years several investigators have independently described unique low-grade renal epithelial neoplasms with clear cytoplasm, focal to diffuse papillary architecture, and occasional leiomyomatous stromal metaplasia that are not currently recognized in the World Health Organization classification of renal tumors. These tumors have been referred to by a variety of names including clear-cell papillary renal cell carcinoma and recently ''clear-cell tubulopapillary renal cell carcinoma''. On the basis of the available data, such tumors are positive for cytokeratin 7 (CK7) and carbonic anhydrase IX (CA9), while being negative for CD10, a-methylacyl-CoA racemase (AMACR), and TFE3. These tumors reportedly lack trisomies of chromosomes 7 and 17, deletions of 3p25, von Hippel-Lindau (VHL) gene mutations, and VHL promoter hypermethylation. Herein, we report on nine cases of this tumor emphasizing detailed studies of the VHL gene and hypoxiainducible factor (HIF) pathway. Molecular studies performed included VHL mutational analysis, copy number changes assessed using single-nucleotide polymorphism arrays, and qRT-PCR for VHL mRNA expression. Immunohistochemical stains for markers of HIF pathway activation (HIF-1a, CA9, and glucose transporter-1 (GLUT-1)) as well as other relevant markers (CK7, CD10, AMACR, and TFE3) were performed. None of our tumors harbored VHL gene mutations, losses of chromosomal region 3p25, or trisomies of chromosomes 7 or 17. VHL mRNA was overexpressed in our tumors relative to normal renal tissue and clear-cell renal cell carcinoma. All cases showed strong co-expression of CK7, HIF-1a, GLUT-1, and CA9. No expression of TFE3, CD10, or AMACR was seen. The morphological, immunophenotypic, and molecular features of these unique low-grade tumors are sufficiently distinct to allow separation from other renal cell carcinoma subtypes. The coexpression of CA9, HIF-1a, and GLUT-1 in the absence of VHL gene alterations in clear-cell papillary renal cell carcinoma suggests activation of the HIF pathway by non-VHL-dependent mechanisms.

show abstract

Section: Aberrationmentioning

confidence: 57%

mentioning

confidence: 99%

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Recently, among patients with clear cell RCC, deletions of 3p were associated with a better prognosis (p ϭ .03) than with loss of 4p, 9p, and 14q, which were associated with a significantly poorer prognosis [63]. In papillary type 1 and type 2 tumors, poorer survival was noted with loss of 9p and 3p, whereas trisomy 17 was associated with a more favorable prognosis [64].…”

Section: Prognostication/predicting Response To Therapymentioning

confidence: 99%

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

2011

Self Cite

View full text Add to dashboard Cite

In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed. The Oncologist 2011;16(suppl 2):4 -13

show abstract

“…Some studies have equally shown that integrating cytogenetic information to existing prognostic factors could lead to a nomogram having an accuracy of 0.89 for predicting disease-specific survival. 27 If these findings are confirmed, renal biopsy might be used more frequently to guide more personalized management.…”

Section: Future Perspectivesmentioning

confidence: 99%

The role of renal biopsy in small renal masses

Burruni

Lhermitte

Cerantola

et al. 2016

CUAJ

View full text Add to dashboard Cite

Renal biopsy is being increasingly proposed as a diagnostic tool to characterize small renal masses (SRM). Indeed, the wide adoption of imaging in the diagnostic workup of many diseases had led to a substantial increased incidence of SRM (diameter ≤4 cm). While modern ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) techniques have high sensitivity for detecting SRM, none is able to accurately and reliably characterize them in terms of histological features. This is currently of key importance in guiding clinical decision-making in some situations, and in these cases renal biopsy should be considered.In this review, we aim to summarize the technique, diagnostic performance, and predicting factors of nondiagnostic biopsy, as well as the future perspectives.

show abstract

Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell Carcinoma

Abstract: This cytogenetic study serves as a proof of principal that genetic information, such as loss of chromosome 9, can be obtained from widely available technology, and can provide additional prognostic information to standard clinicopathologic variables.

Cited by 184 publications

References 43 publications

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

The role of renal biopsy in small renal masses

Contact Info

Product

Resources

About