Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Kluger, Harriet M.; Siddiqui, Summar; Angeletti, Cesar; Sznol, Mario; Kelly, William Kevin; Molinaro, Annette M.; Camp, Robert L.

doi:10.1038/labinvest.2008.65

Cited by 47 publications

(40 citation statements)

References 21 publications

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“…Two separate tissue microarray (TMA) sets were constructed using archival, surgical material from non-overlapping resected RCC cases that have been described previously 25 26. Cohort A consisted of a large series of patients (n=334) with renal tumours resected between 1987 and 1999 and included a total of two 0.6 mm cores from the tumour.…”

Section: Methodsmentioning

confidence: 99%

“…Cohort A consisted of a large series of patients (n=334) with renal tumours resected between 1987 and 1999 and included a total of two 0.6 mm cores from the tumour. Two hundred and ninety-four of the patients had a matched normal adjacent kidney core 26. The cohort included clear cell RCC (71%), papillary RCC (14%), oncocytoma (6%), chromophobe RCC (2%), as well as unclassified/other histologies (7%).…”

Section: Methodsmentioning

confidence: 99%

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PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

et al. 2014

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Aims Immunohistochemical stains have greatly improved the diagnostic accuracy of renal cell carcinoma (RCC) for primary and distant tumours. We evaluate a marker that has recently been incorporated in clinical practice, PAX-8, in primary and metastatic RCCs. Methods Two distinct tissue microarrays were used, one consisting of over 334 renal tumours, 294 with adjacent normal kidney and the other with 40 matched nephrectomy and metastatic sites of RCC. PAX-8 expression was assessed by a method of quantitative immunofluorescence. Results PAX-8 was positive in 96% (146/152) of normal renal tissue and 83% (227/272) of renal tumours. PAX-8 staining was positive in clear cell, papillary and chromophobe tumours in 80% (165/207), 95% (39/41) and 100% (6/6) of samples, respectively. Overall, intensity of PAX-8 expression was significantly higher in RCC metastatic sites than in the primary site (p=0.0047), however, in matched sites there was no statistically significant difference in the proportion of positive versus negative specimens (p=0.274). Conclusions As the role of molecular markers expands in the diagnostic algorithm, this study confirms that PAX-8 expression is a useful diagnostic marker for RCC. PAX-8 expression was found in the primary tumour and distant sites. Compared with normal tissue and other histological types, clear cell RCC has lower PAX-8 expression and is less frequently positive, therefore, the lack of expression does not exclude a tumour of renal origin.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

et al. 2014

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“…Yang et al described a link between hypoxia, HIF-1α and the transcription factor TWIST, 67 to strongly correlate with microvessel density, a measure of the degree of angiogenesis. 29 A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells such as VEGFR and PDGFR. Other HIF targets include genes involved in glucose metabolism (Endoglin and others), 20 cell proliferation and survival (TGFα and EGFR) and metastasis (MUC1).…”

Section: Epithelial To Mesenchymal Transition (Emt)mentioning

confidence: 99%

Signaling pathways in renal cell carcinoma

Gowrishankar

Cairns

2010

Cancer Biology & Therapy

188

139

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“…As secondary antibodies we used mouse EnVision reagent (DAKO, neat) and Alexa 546 conjugated goat anti-rabbit secondary antibody (Molecular Probes, Eugene, OR; 1:100) for targeting ALDH1 as a single target. For multiple targets we used mouse EnVision and rabbit EnVison (DAKO, neat), after blocking horseradish peroxidase as previously described, 34 and Alexa Fluor 546 goat anti-guinea pig secondary antibody (Molecular Probes) for 1 hour at room temperature. Cy5-tyramide (Perker Elmer, Life Science, MA) and biotinylated tyramide (Perker Elmer) followed by streptavidinconjugated Alexa Fluor 750 (Invitrogen, Molecular Probes) were used to visualize the targets.…”

Section: Multiplexed Immunohistochemical Staining For Single Target mentioning

confidence: 99%

In Situ Identification of Putative Cancer Stem Cells by Multiplexing ALDH1, CD44, and Cytokeratin Identifies Breast Cancer Patients with Poor Prognosis

Neumeister

Agarwal

Bordeaux

et al. 2010

The American Journal of Pathology

138

100

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A subset of cells, tentatively called cancer stem cells (CSCs), in breast cancer have been associated with tumor initiation, drug resistance, and tumor persistence or aggressiveness. They are characterized by CD44 positivity, CD24 negativity, and/or ALDH1 positivity in flow cytometric studies. We hypothesized that the frequency or density of these cells may be associated with more aggressive tumor behavior. We borrowed these multiplexed, flow-based methods to develop an in situ method to define CSCs in formalin-fixed paraffin-embedded breast cancer tissue, with the goal of assessing the prognostic value of the presence of CSCs in breast cancer. Using a retrospective collection of 321 nodenegative and 318 node-positive patients with a mean follow-up time of 12.6 years, we assessed TMAs using the AQUA method for quantitative immunofluorescence. Using a multiplexed assay for ALDH1, CD44, and cytokeratin to measure the coexpression of these proteins, putative CSCs appear in variable sized clusters and in 27 cases (of 490), which showed significantly worse outcome (log rank P ‫؍‬ 0.0003). Multivariate analysis showed that this marker combination is independent of tumor size, histological grade, nodal status, ER-, PR,-and HER2-status. In this cohort, ALDH1 expression alone does not significantly predict outcome. We conclude that the multiplexed method of in situ identification of putative CSCs identifies high risk patients in breast cancer.

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Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Cited by 47 publications

References 21 publications

PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

Signaling pathways in renal cell carcinoma

In Situ Identification of Putative Cancer Stem Cells by Multiplexing ALDH1, CD44, and Cytokeratin Identifies Breast Cancer Patients with Poor Prognosis

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