The EGFR-KRAS-BRAF-MEK-ERK (MAPK) pathway plays an important role in most cancers with close association of EGFR, KRAS or BRAF mutations with carcinogenesis and drug resistance. EGFR have been developed for molecular targeted therapy of various cancers. However, it remains to be determined whether aberration of this pathway is essential for the survival of clear cell renal cell carcinoma (CCRCC) and whether EGFR tyrosine kinases inhibitors (TKIs) could benefit CCRCC patients. In this study, we

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... etect EGFR, KRAS and BRAF mutations in CCRCC, investigate the potential of EGFR TKIs for the treatment of CCRCC patients, and summarize clinicopathological characteristics of CCRCC carrying EGFR, KRAS and BRAF mutations. EGFR, KRAS and BRAF mutation in 100 CCRCC from China were detected by high resolution melting analysis. Positive mutations were confirmed using direct se-quencing. The cases with EGFR, KRAS and BRAF mutations were further assessed by immunohistochemistry (IHC). The diagnosis of CCRCC was confirmed by IHC staining of CK (Pan), EMA, Vimentin, CD10, Desmin and SMA, and the activation of MAPK pathway was assessed by IHC staining of EGFR, KRAS, BRAF and p-BRAF. One KRAS while no EGFR or BRAF mutations were identified in these 100 CCRCC patients. The case with KRAS mutation was histologic grade G4, tumor stage III and TNM stage III (T3N0M0). Lung metastasis was found four months after surgery and the patient died two and a half months after metastasis. The tumor with KRAS mutation was positive for CK (Pan), EMA, Vimentin, CD10, but negative for desmin and SMA, and positive for KRAS, BRAF, and p-BRAF, but negative for EGFR. To conclude, our results support EGFR, KRAS and BRAF mutations are rare in CCRCC, EGFR TKIs may be not suitable for the majority of CCRCC patients and CCRCC patients with the tumor carrying KRAS mutation might have poor prognosis.