Cellular and Molecular Biology


Utility of immunohistochemical investigation of SDHB and molecular genetic analysis of SDH genes in the differential diagnosis of mesenchymal tumors of GIT

M. Dubova1, M. Sedivcova2, M. Michal1, B. Kokoskova1,2, A. Ryska3, D. Smid4 and O. Daum1,2

1Siklīs Department of Pathology, Medical Faculty Hospital, Charles University, Plzen, 2Biopticka laborator s.r.o., Plzen, 3The Fingerland Department of Pathology, University Hospital, Hradec Kralove and 4Surgical Clinic, Medical Faculty Hospital, Charles University, Plzen, Czech Republic

Offprint requests to: Ondrej Daum, M.D., Ph.D., Sikl's Department of Pathology, Medical Faculty Hospital, Charles University, Edvarda Benese 13, Plzen, 305 99, Czech Republic. e-mail: daum@fnplzen.cz

Summary. Loss of expression of beta subunit of succinate dehydrogenase (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastro-intestinal stromal tumors (GISTs). To evaluate possible diagnostic utility of SDHB immunohistochemistry in the differential diagnostics of mesenchymal tumors of gastrointestinal tract (GIT), 11 cases of KIT/PDGFRA wt GISTs, 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 investigated for SDHB immunoexpression together with molecular genetic analysis of genes encoding succinate dehydrogenase (SDH). Three recent cases of KIT/PDGFRA mutant GISTs were used as controls. Among the 11 KIT/PDGFRA wt GISTs, 6 expressed SDHB, 1 of them harboring a sequence change of SDHD. All SDHB-negative cases were SDHB-D wt. In 1 of the control GIST cases molecular genetic analysis revealed an SDHD sequence change in addition to a mutation in KIT exon 11. No SFT was truly SDHB-negative, but in 2 of them the staining was impossible to analyze. Furthermore, 1 SFT carried an SDHB and another 1 SDHD sequence change. All GSs, LMs, LMSs, SSs, ESSs, and IMT were SDHB-positive or non-analyzable, and SDHB-D wt. Additional factors may play a role in regulating expression of SDHB. Furthermore, SDHB immuno-histochemistry alone may be misleading in excluding tumors other than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT. Histol Histopathol 30, 223-232 (2015)

Key words: GIST, Stromal tumor, KIT, PDGFRA , SDH

DOI: 10.14670/HH-30.223