Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms.

Authors

Markku Miettinen, Laboratory of Surgical Pathology, National Cancer InstituteFollow
Maarit Sarlomo-Rikala, Department of Pathology, Haartman Institute, Helsinki University HospitalFollow
Peter McCue, Department of Pathology and Cell Biology, Jefferson Medical College, Thomas Jefferson UniversityFollow
Piotr Czapiewski, Department of Pathomorphology, Medical University of Gdansk
Renata Langfort, Department of Pathology, National Tuberculosis and Lung Diseases Research InstituteFollow
Piotr Waloszczyk, Independent Laboratory of Pathology, Zdunomed
Krzysztof Wazny, Department of Pathomorphology, Medical University of Gdansk
Wojciech Biernat, Department of Pathomorphology, Medical University of Gdansk
Jerzy Lasota, Laboratory of Surgical Pathology, National Cancer Institute
Zengfeng Wang, Laboratory of Surgical Pathology, National Cancer InstituteFollow

Document Type

Article

Publication Date

1-1-2014

Comments

This article has been peer reviewed. It was published in: Applied Immunohistochemistry and Molecular Morphology

Volume 22, Issue 1, January 2014, Pages 31-36.

The published version is available at DOI: 10.1097/PAI.0b013e31828bfdd3

Copyright © 2013 by Lippincott Williams and Wilkins

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.

Recommended Citation

Miettinen, Markku; Sarlomo-Rikala, Maarit; McCue, Peter; Czapiewski, Piotr; Langfort, Renata; Waloszczyk, Piotr; Wazny, Krzysztof; Biernat, Wojciech; Lasota, Jerzy; and Wang, Zengfeng, "Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms." (2014). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 157.
https://jdc.jefferson.edu/pacbfp/157

PubMed ID

23531856