Utility of Immunohistochemical Investigation of SDHB and Molecular Genetic Analysis of SDH Genes in the Differential Diagnosis of Mesenchymal Tumors of GIT
Ondrej Daum, Monika Sedivcova, Magdalena Dubova, Michal Michal. Medical Faculty Hospital, Charles University, Plzen, Czech Republic
Background: In 2010 loss of expression of succinate dehydrogenase B (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastrointestinal stromal tumors (GISTs), mainly those associated with Carney trias or occurring in childhood or young adulthood. Later it was found out that these tumors may harbour inactivating germline mutations of genes encoding subunits od SDH (SDHB-D). To evaluate possible diagnostic utility of SDHB immunohistochemistry and molecular genetic analysis of SDHB-D we performed this study.
Design: Eleven cases of KIT/PDGFRA wt GISTs (7 gastric, 4 intestinal), 12 gastric schwannomas (GSs), 20 solitary fibrous tumors (SFTs), 4 leiomyomas (LMs), 16 leiomyosarcomas (LMSs), 5 synovial sarcomas (SSs), 3 endometrioid stromal sarcomas (ESSs), and 1 ileal inflammatory myofibroblastic tumor (IMT) were retrieved from our archives. Three recent cases of KIT or PDGFRA mut GISTs were used as control cases. SDHB immunoexpression of all tumors was compared with molecular genetic profiles of cases containing DNA of sufficient quality. In GIST cases, their pattern was compared with previous markers.
Results: Among the 11 KIT/PDGFRA wt GISTs, 5 tumors were SDHB+. Of these, 2 were of epithelioid type, and none showed mutations in SDHB-D. Among the 6 SDHB- cases, only 1 was of spindle cell type, and no SDHB-D mutations were identified. Interestingly, in 1 of the control GIST cases, which was located in the mediastinum, showed epithelioid morphology and was SDHB-, molecular genetic analysis revealed an SDHD sequence change (G12S) with questionable pathogenicity in addition to W557_E561del of exon 11 of KIT. Five SFTs were SDHB-, one of them carried an SDHB sequence change (S163P) with questionable pathogenicity. Among the 15 SDHB+ cases of SFTs, one tumor also carried a G12S sequence change of SDHD. Two GSs, 1 LM, 2 LMSs, and 1 SS were SDHB-, but no SDHB-D mutations were identified in these types of tumor. All 3 ESSs and 1 IMT were SDHB+ and without identifiable SDHB-D mutations.
Conclusions: Based on the comparison of SDHB-D genotype and SDHB immunoexpression, it may be hypothesized that other additional genetic and epigenetic factors may play a role in regulating expression of SDHB. Furthermore, the study showed that SDHB immunohistochemistry alone is not sufficient to exclude other tumors than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 68, Wednesday Morning