Expression Of Succinate Dehydrogenase Subunit Protein And Detection Of Gene Mutation In Succinate Dehydrogenase-deficient Renal Cell Carcinoma

Objective: To analyze the relationship between the subunit protein expression and gene mutation,and to explore the relationship between the deficiency of protein expression and clinicopathologic features in succinate dehydrogenasedeficient renal cell carcinoma(SDH-deficient RCC).Methods: Immunohistochemical study was performed in 214 cases of RCC by using the EnVision method.Cases of SDH-deficient RCC were further screened.Polymerase chain reaction(PCR)was used to amplify exon 3 of SDHA gene,exon 1,3,4,5,6 and 7 of SDHB gene,exon 1 and 3 of SDHC gene,and exon 1,2 and 3 of SDHD gene;then DNA direct sequencing analysis was used for detecting its mutation.Cases of SDH-deficient RCC were further analyzed for clinicopathologic features.Results: Seven SDH-deficient(negative)RCC were found in all 214 cases of RCC(3.3%,7/214).Two were male and five were female with a female predominance(M:F=1:2.5).The patients ranged in age from 41 to 77 years old(median=56 years old,mean=56 years old).Three cases had tumor located in left kidney and 4 cases had tumor in right kidney.Among the seven cases of SDH-deficient RCC,2(0.9%,2/214)were found negative with SDHA,3(1.4%,3/214)were found negative with SDHB,1(0.5%,1/214)SDHC-deficient(negative)RCC and 1(0.5%,1/214)SDHD-deficient RCC were also found.The unique pathological characteristics of the seven cases of SDH-deficient RCC were as following: Five cases were clear cell renal cell carcinoma(CCRCC)with low grade nucleus,one was chromophobe renal cell carcinoma(ChRCC)and the last one was papillary renal cell carcinoma(PRCC);The tumor cells were round or polygonal with clear or eosinophilic cytoplasm,and cytoplasmic eosinophilic flocculent material could be seen;Five cases belonged to low grade nucleus including WHO/ISUP G1 and G2.The expression of SDHx protein was found positive in the left 207 cases.All cases were successfully amplified by PCR in the SDH-deficient RCC and they all had SDHB gene mutations.6 cases had SDHB gene exon 1 point mutation,5 cases had SDHB gene exon 4 mutation,1 case had SDHB gene exon 3 point mutation and one case had SDHB gene exon 6 mutation.The rest exons of the SDHx gene were wild-type sequence.Conclusion: SDH-deficient RCC has distinctive clinicopathologic characteristics,and most of them belong to clear cell renal cell carcinoma with low grade nucleus.Genetic detecting is necessary for the cases of SDHx protein expression deficiency(negative).