title: Inverse correlation of aberrant expression of fragile histidine triad (FHIT) protein with cyclin D1 protein and prognosis in Chinese patients with cholangiocarcinoma.
abstract: BACKGROUND
  This is the first study to explore the relationship between the expression of fragile histidine triad, FHIT and cyclin D1 proteins, and the clinicopathological significance of the two proteins in Chinese patients with cholangiocarcinoma.
  
  
  METHODS
  Immunohistochemistry was used to study 53 cases of cholangiocarcinoma, 30 para-neoplastic and 20 normal bile ducts for their expression status of FHIT and cyclin D1 and then the results were analyzed with the patient's age, sex, tumour site, histological grade and clinical stage as well as overall median survival time.
  
  
  RESULTS
  Compared with the para-neoplastic and normal cholangiocytes, the expression of FHIT was obviously decreased (p=0.0001), whereas that of cyclin D1 was significantly increased (p=0.0001) in carcinoma cells. The expression of FHIT was found to be correlated with the histological grade (p=0.007) and the clinical stage (p=0.004), but not with age (p=0.776), sex (p=0.246) or tumour site (p=0.347). The expression of cyclin D1 was also showed statistically associated with the histological grade (p=0.043) and clinical stage (p=0.047), but not with age (p=0.965), sex (p=0.751) or tumour site (p=0.948). Further, the expression of FHIT was found to be inversely correlated with the expression of cyclin D1 (p=0.0001). The loss of expression of FHIT and the expression of cyclin D1 were significantly related to the cancers with shorter median survival time (p=0.0001, p=0.0081). The expression of FHIT was an independent prognostic factor (p=0.005).
  
  
  CONCLUSIONS
  The expression of FHIT may be inversely correlated with the expression of cyclin D1. It is suggested that the loss of FHIT protein and overexpression of cyclin D1 protein may play an important role in carcinogenesis and prognosis of cholangiocarcinoma.
authors.affiliation: Department of Pathology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China. zhaopo@301hospital.com.cn
authors.forename: Po
authors.initials: P
authors.lastname: Zhao
authors.forename: Yali
authors.initials: Y
authors.lastname: Lu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism*; D015331:Cohort Studies; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D019938:Cyclin D1; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C530104:CCND1 protein, human