Comparative Study With Sarcomatoid Renal Cell Carcinoma Tissue Differentiation Between The Two Kinds Of Vhl Gene Mutation, Vhl/hif Pathway Of Protein Expression

BACKGROUND&OBJECTIVE:Renal cell carcinoma with sarcomatoid differentiation (SRCC) is an uncommon neoplasm.Sarcomatoid differentiation can be found in all subtypes of RCC. The mutation of von Hippel-Lindau (VHL) tumor suppressor gene is closely related with tumorigenesis of clear cell renal cell carcinoma (CCRCC).But the reports of VHL gene mutation incidence was different in many researchs, and there is a dispute about the relationship between prognosis with clinicopathological features. Futhermore the molecular mechnism of VHL gene mutation with RCC is not fully understood. We studied VHL gene mutation and pVHL, HIF-la and VEGF immunohistochemistry of21cases of renal cell carcinoma with sarcomatoid differentiation and16cases of clear cell renal cell carcinoma. Especially discriminate epithelial components and sarcomatous components by manual microdissection. This study was to determine the mutation of VHL gene in renal cell carcinoma with sarcomatoid differentiation in Chinese people, explore the characteristics of the VHL tumor suppressor gene mutation and its relationship with clinicopathological features, provide important information for the further study of the molecular mechanism of renal cell carcinoma with sarcomatoid differentiation.METHODS:We retrospectively reviewed21patients treated for SRCC and16patients for CCRCC in Fudan University Shanghai Cancer Center between2007and2011. Manual microdissection, polymerase chain reaction (PCR) bi-directional sequencing and immunohistochemical method were used to detect the mutation of VHL gene and the expression of pVHL, HIF-la and VEGF. The data obtained were statistically analyzed using statistical software SPSS13.0.RESULTS:1.Of the21specimens of SRCC,2(9.5%) had various VHL gene mutations.Substitution mutation in1case, insertional mutation in1case. One was located in exon1, one in exon2. Two mutations exist in both the epithelial components and sarcomatous components. Of the16specimens of ccRCC,3(18.8%) had various VHL gene mutations. Substitution mutation in2case, deletion mutation in1case.One was located in exon1, one in exon2and one in exon3.2. In21cases of renal cell carcinoma with sarcomatoid differentiation of tissues, the immunohistochemical results as follows:pVHL-positive rate was11/21(52.4%); HIF-la positive rate was16/21(76.2%); VEGF positive rate4/21(19.0%). The sarcomatoid and epithelial tumor components in all21cases showed concordant p-VHL, HIF-la and VEGF expression patterns. In16cases of clear cell renal cell carcinoma, p-of VHL of HIF-la and VEGF positive rate:8/16(50.0%),10/16(62.5%), and2/16(12.5%).CONCLUSION:The percent of the mutation of VHL gene in renal cell carcinoma with sarcomatoid differentiation is very low, there may be other genes involved in the process of sarcomatoid differentiation. Both the sequencing results and the immunohistochemical results suggest that the epithelial components and sarcomatous components in renal cell carcinoma with sarcomatoid differentiation may share the same origin.