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Open Access Research article

Expression of drug targets in primary and matched metastatic renal cell carcinoma tumors

Saadia A Aziz1, Joshua A Sznol1, Adebowale Adeniran2, Fabio Parisi2, Yuval Kluger2, Robert L Camp2 and Harriet M Kluger1*

Author Affiliations

1 Department of Medicine and Yale Cancer Center, 333 Cedar St., WWW213, New Haven, CT, 06520, USA

2 Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

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BMC Clinical Pathology 2013, 13:3  doi:10.1186/1472-6890-13-3

Published: 1 February 2013

Abstract

Background

Targeted therapies in renal cell carcinoma can have different effects on primary and metastatic tumors. To pave the way for predictive biomarker development, we assessed differences in expression of targets of currently approved drugs in matched primary and metastatic specimens from 34 patients.

Methods

Four cores from each site were embedded in tissue microarray blocks. Expression of B-Raf, C-Raf, cKIT, FGF-R1, HIF-2α, mTOR, PDGF-Rβ, VEGF-R1, VEGF-R2, VEGF-R3, VEGF, VEGF-B, VEGF-C, VEGF-D, MEK1, and ERK1/2 was studied using a quantitative immunofluorescence method.

Results

No significant differences were observed in global expression levels in primary and metastatic renal cell carcinoma tumors, with the exception of MEK, which had higher expression in metastatic than primary specimens. Similarly, more ki67 positive cells were seen in metastatic specimens. Correlations between marker expression in primary and metastatic specimens were variable, with the lowest correlation seen for FGF-R1 and VEGF-D. There were no significant differences in the degree of heterogeneity in primary versus metastatic tumors.

Conclusions

Expression of most of the studied markers was similar in primary and metastatic renal cell carcinoma tumors, suggesting that predictive biomarker testing for these markers can be conducted on either the primary or metastatic tumors for most markers.

Keywords:
Renal cell carcinoma; Targeted therapy; Predictive biomarkers; VEGF