Abstract

A subset of renal cell carcinoma (RCC) patients has been shown to respond to anti-EGFR therapy. As KRAS and BRAF mutations are associated with poor response to anti-EGFR therapy in some cancers, it has been suggested that screening for KRAS and BRAF mutations in RCC may be a promising strategy to identify patients who might respond to EGFR-targeted therapy. The aim of this study was to investigate the mutation status of EGFR, KRAS and BRAF in RCC patients. Renal tumors and normal renal samples from forty-eight patients who underwent radical or partial nephrectomy for kidney cancer were used in this study. Histological classification of the tumors was performed according to International Union against Cancer (UICC) / American Joint Committee on Cancer (AJCC) classification. Seventeen patients (48%) had clear-cell RCC, 7 (20%) had chromophobe RCC, and 11 patients (32%) had papillary RCC. DNA isolated from the samples was subjected to melting curve mutation analysis for EGFR, BRAF and KRAS using ABI-3130 DNA sequencer. DNA sequencing analysis of RCC samples, when compared with morphologically normal matched regions, did not show any exon mutations. Our results do not support the notion that EGFR, KRAS and BRAF might be mutated in RCC.

Highlights

  • Renal cell carcinoma (RCC) constitutes 3% of all adult malignancies [1]

  • As KRAS and BRAF mutations are associated with poor response to anti-epidermal growth factor receptor (EGFR) therapy in some cancers, it has been suggested that screening for KRAS and BRAF mutations in RCC may be a promising strategy to identify patients who might respond to EGFR-targeted therapy

  • Our results do not support the notion that EGFR, KRAS and BRAF might be mutated in RCC

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Summary

Introduction

Renal cell carcinoma (RCC) constitutes 3% of all adult malignancies [1]. According to Surveillance, Epidemiology, and End Results (SEER) data, the annual increase in RCC incidence is 2.5-3%, as we have started to use modern imaging methods more frequently since 1970s [2]. 60% of new diagnoses are coincidental, 25% of the patients are metastatic during the diagnosis [3]. Radical nephrectomy or nephron sparing surgery is the standard treatment for localized RCC, while 30% of the patients experience recurrence after the surgery [3]. Despite the tremendous improvements in our understanding of the molecular mechanisms of RCC, and the introduction of many novel multi-tyrosine kinase inhibitors in clinical practice for the treatment of RCC the five-year survival of metastatic patients continues to be less than 10%. There is a need for a better understanding of the molecular mechanisms of RCC and the discovery of more efficient therapeutics for the management of metastatic RCC. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor of the Erb family, is overexpressed in both

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