关键词: 癌, 肾细胞, MAP激酶信号系统, 肿瘤转移, 骨, 突变

Abstract:

Objective： To investigate the expression of MEK/ERK signaling pathways in renal cell carcinoma with bone metastasis, and to analyze the differences of expressions of VEGFR-2, MEK, ERK on the primary and metastasis tissue and its mechanism. Methods: The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology, Peking University People’s Hospital from January 1, 2009 to January 1, 2010. The expression of MEK/ERK signaling pathways was detected in the 7 renal cell carcinoma patients` primary and matched metastatic tissues with ICH, The antibody concentrations were 1 ∶200, 1 ∶25, and 1 ∶250, respectively. The mutation of the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the se-cond exon of the MEK1 gene were detected with PCR.  Results: The expression intensities of VEGFR-2, MEK, and ERK were measured by H-score ［intensity (1, 2, 3, or 4) multiplied by the distribution (%)］. VEGFR-2, MEK, and ERK expressions were divided into 3 groups according to the positive distribution of the tumor cells: 1, 0－5%; 2, 6%－50%; and 3, >50%, To assess intratumor heterogeneity, three distinct microscopic fields (×200) from each specimen were used to evaluate the expressions, Subsequently, the scores were averaged to obtain a single concatenated score for each tissue. VEGFR-2, MEK, and ERK expressions were assessed by 2 independent pathologists who were blinded to the clinicopathological data. The data were expressed as the mean value of the triplicate experiments. The expressions of MEK, and ERK were higher in the metastatic tissues than in the matched RCC tissues (6.10±4.10 vs.  1.33±0.51, P=0.015; 9.10±2.24 vs. 4.43±2.84, P=0.021) while the expression of VEGFR2 was not different between the primary and metastatic tissues (P=0.901). No mutation was detected on the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the second exon of the MEK1 gene. Conclusion: MEK/ERK signaling pathways may play an important role in the metastasis and the resistance of sunitinib in RCC patients with bone metastasis.

Key words: Carcinoma, renal cell, MAP kinase signaling system, Neoplasm metastasis, Bone, Mutation