title: Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms.
abstract: Losses in the succinate dehydrogenase (SDH) complex characterize 20% to 30% of extra-adrenal paragangliomas and 7% to 8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%), including a patient with an SDHB-deficient GIST. Histologically, the SDHB-negative renal carcinomas varied. There was 1 clear cell carcinoma with a high nuclear grade, 1 papillary carcinoma type 2, 1 unclassified carcinoma with a glandular pattern, and 1 oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, 1 in the retroperitoneal lymph nodes). There were no cases with SDHB loss among 64 renal oncocytomas. SDHB losses were not seen in other carcinomas, except in 1 prostatic adenocarcinoma (1/57), 1 lymphoepithelial carcinoma of the stomach, and 1 (1/40) seminoma. On the basis of this study, SDHB losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study.
authors.affiliation: *Laboratory of Surgical Pathology, National Cancer Institute, Bethesda, MD †Department of Pathology/Haartman Institute and HusLab, Helsinki University Hospital, Helsinki, Finland ‡Department of Pathology and Cell Biology, Jefferson Medical College of Thomas Jefferson University and University Hospital, Philadelphia, PA §Department of Pathomorphology, Medical University of Gdansk, Gdansk ∥Department of Pathology, National Tuberculosis and Lung Diseases Research Institute, Warsaw ¶Independent Laboratory of Pathology, Zdunomed, Szczecin, Poland.
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.forename: Maarit
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: Peter
authors.initials: P
authors.lastname: McCue
authors.forename: Piotr
authors.initials: P
authors.lastname: Czapiewski
authors.forename: Renata
authors.initials: R
authors.lastname: Langfort
authors.forename: Piotr
authors.initials: P
authors.lastname: Waloszczyk
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wazny
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lasota
authors.forename: Zengfeng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase