title: [Expression of SDHB, EPAS1 and MIB-1 in Zuckerkandl paragangliomas].
abstract: OBJECTIVE
  To explore the significance of succinate dehydrogenase B (SDHB) mutation and EPAS1 overexpression in Zuckerkandl paragangliomas (PGL) and examine their correlations with malignant infiltration and metastasis.
  
  
  METHODS
  From March 2008 to July 2011, the clinical profiles of 16 Zuckerkandl PGL patients were analyzed retrospectively. For increased diagnostic specificity, a complex immunohistochemical panel of tissue microarray was performed for SDHB, EPAS1 and MIB-1. Positive expression identified as a granular cytoplasmic staining. Greater than or equal to 50% as strongly positive (+++), 1% to 10% as weakly positive (+).
  
  
  RESULTS
  Tissue microarray immunohistochemical staining showed SDHB immunoreactivity in the cytoplasm, whereas EPAS1 and MIB-1 in the nuclear of tumor cells. Positive expression of EPAS1 in which 13 cases of Zuckerkandl PGL. And high expression strongly associated with malignancy. SDHB mutation of 7 cases are all EPAS1 positive staining. Non-gene mutation 9 cases tumor specimens, 6 cases were EPAS1 positive expression (P < 0.05). CgA positive expression in 11 cases benign Zuckerkandl PGL, strongly positive in 4 malignant cases (4/4). MIB-1 below 1% in 12 cases of benign Zuckerkandl PGL. And in 4 malignant cases, MIB-1 was about 3%. Malignant neoplasms had significantly higher EPAS1, CgA and MIB-1 expression compared to benign counterparts (P < 0.05).
  
  
  CONCLUSIONS
  The SDHB mutation causes the EPAS1 over expression in PGL and correlation with higher positive expression of CgA and MIB-1. It may be one of the mechanisms of malignant invasiveness and metastasis in PGL.
authors: Department of Urology & Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors: Jian-hua
authors: JH
authors: Deng
authors: Han-zhong
authors: HZ
authors: Li
authors: Yu-shi
authors: YS
authors: Zhang
authors: Wei-feng
authors: WF
authors: Xu
authors: Quan-cai
authors: QC
authors: Cui
mesh_terms: D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010220:Para-Aortic Bodies / Q000473:pathology; D010236:Paraganglioma, Extra-Adrenal / Q000378:metabolism* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D046888:Tissue Array Analysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D055815:Young Adult; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019394:Ki-67 Antigen; D013385:Succinate Dehydrogenase; D044767:Ubiquitin-Protein Ligases; D000099162:Endothelial PAS Domain-Containing Protein 1; C108095:SDHB protein, human; C513496:MIB1 ligase, human