title: Fragile histidine triad expression in oral squamous cell carcinoma and precursor lesions.
abstract: OBJECTIVE
  Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHIT expression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival.
  
  
  METHODS
  Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes.
  
  
  RESULTS
  By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (chi2=13.8; degrees of freedom=4; P=0.008). Loss of FHIT expression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (chi2=3.8; degrees of freedom=1; P=0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P=0.546, Kaplan-Meier, log-rank).
  
  
  CONCLUSIONS
  FHIT seems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.
authors.affiliation: School of Dentistry, The University of Manchester, North Manchester General Hospital, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Kujan
authors.forename: Richard
authors.initials: R
authors.lastname: Oliver
authors.forename: Luca
authors.initials: L
authors.lastname: Roz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.forename: Noel
authors.initials: N
authors.lastname: Ribeiro
authors.forename: Robert
authors.initials: R
authors.lastname: Woodwards
authors.forename: Nalin
authors.initials: N
authors.lastname: Thakker
authors.forename: Philip
authors.initials: P
authors.lastname: Sloan
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D016019:Survival Analysis; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase