title: Downregulation of fumarate hydratase is related to tumorigenesis in sporadic renal cell cancer.
abstract: OBJECTIVE
  Although germline mutations of fumarate hydratase (FH) are a useful molecular marker of hereditary leiomyomatosis and renal cell cancer (RCC) syndrome, their clinical significance in sporadic RCC has not been studied in detail. The aim of the present study was to investigate possible correlations between the expression of FH and the clinical implications of sporadic RCC.
  
  
  METHODS
  FH mRNA levels were evaluated in 140 tumor specimens from patients with primary RCC and in 62 specimens of corresponding normal-appearing kidney tissue using real-time quantitative polymerase chain reaction. Immunohistochemical staining was performed on 6 normal surrounding tissues and 71 RCC tissues.
  
  
  RESULTS
  FH mRNA levels were significantly lower in tumor tissues than in matched normal-appearing kidney tissues (p = 0.031). In all normal tissues, FH staining intensity was strong. However, the expression of FH showed no significant correlation with the pathological and clinical characteristics of patients with sporadic RCC.
  
  
  CONCLUSIONS
  Our results showed that FH mRNA expression decreased significantly in correlation with the transition from normal renal parenchyma to RCC. FH may be an indicator or tumorigenesis in sporadic RCC and could be a potential target for therapies against RCC in the future.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Yun-Sok
authors.initials: YS
authors.lastname: Ha
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.forename: Hyung-Yoon
authors.initials: HY
authors.lastname: Yoon
authors.forename: Yong-June
authors.initials: YJ
authors.lastname: Kim
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Woo
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005649:Fumarate Hydratase / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D005649:Fumarate Hydratase