Expression Of Succinate Dehydrogenase Subunit Protein And Detection Of Gene Mutation In Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors

Objective:To analyze the relationship between the loss of protein expression and its gene mutations,and to explore the relationship between protein expression loss and clinicopathologic features and prognosis,and to provide theoretical guidance for the treatment of succinate dehydrogenase-deficient gastrointestinal stromal tumors(SDH-deficient GISTs)by detecting the expression and gene mutation of succinate dehydrogenase subunits in SDH-deficient GISTs.Methods: The immunohistochemical EnVision technique was used to detect the expression of succinate dehydrogenase(SDH)subunits in tumor tissues of GISTs;polymerase chain reaction(PCR)was used to amplify exon 9 of SDHA gene,and exon 1,2,3,4,5,6 and 7 of SDHB gene,and exon 1 and 3 of SDHC gene,and exon1,2 and 3 of SDHD gene,then DNA sequencing was used to detect its mutations;and clinical data analysis and followed-up were performed on the proteins expression defect(negative)GISTs cases.Results: In 171 cases of GISTs,162 cases of SDHB protein were found to be positive,accounting for 94.7%(162/171);and 9 cases were found to be SDHBdeficient(negative),accounting for 5.3%(9/171).With in the 9 cases SDHB-deficient(negative)GISTs,2 were male and 7 were female;the age of initial diagnosis was 15 to 78 years(median =39 years,mean=41 years);tumors all involved the stomach;the diameter of tumor varied from 0.5 to 15.0cm(mean=6.9cm);epithelioid cell type,spindle cell type and mixed cell type were 3 cases respectively;4 cases were multinodularity(plexiform)in the wall of stomach.1 case was found to beintraperitoneal implantation metastasis,1 case was found to have vascular invasion,and the other 7 patients had no vessel invasion and metastasis.Among SDHB-deficient GISTs,2 SDHA-deficient(negative)cases were found(1.2%,2/171)and none of SDHC and SDHD deficient(negative)GISTs was found.7 cases were successfully amplified by PCR in 9 cases of SDHB deficient(negative)and they all had SDHB gene mutations.4 cases had an SDHB gene exon 1 point mutation,1 case had an SDHB gene exon 7 insertion mutation.1 case not only had an exon 1 mutation but also a heterozygous mutation in the exon 4 in SDHB gene.1 case had an exon 1mutation and an exon 6 deletion mutation in the SDHB gene.The rest of the gene exons were wild-type sequences.Five of the nine SDH-deficient GISTs had followed-up data: one died 8 months after surgery of unknown cause,four did not recur or metastasize and no history of paraganglioma and pulmonary chondroma was found in them and their families.No mutation in CKIT and PDGFRA gene was discovered in 9 cases of SDH-deficient GISTs.Conclusion: SDH-deficient GISTs has unique clinicopathologic features and a favorable prognosis,and a small proportion of cases are SDHA-deficient,no SDHCand SDHD-deficient case is found.It is necessary to detect its genes to guide the treatment in the SDHx-deficient(negative)GISTs.