title: The expression of FHIT in salivary carcinoma ex pleomorphic adenoma.
abstract: BACKGROUND
  Carcinoma ex-pleomorphic adenoma (Ca-ex-PA) is considered to be a malignant transformation product of pre-existing pleomorphic salivary adenoma (PSA).
  
  
  OBJECTIVE
  Our study aimed to characterise alterations in the immunohistochemical expression of the Fragile Histidine Traid (FHIT) and Cyclin-dependent Kinase Inhibitor 2A (CDKN2A) (p16(INK4a)) genes during tumour progression model from PSA to Ca-ex-PA in a cross sectional study.
  
  
  METHODS
  Paraffin blocks of 29 cases of PSA which were surrounded by normal parotid gland, and 26 cases of Ca-ex-PA were retrieved and validated. In all cases of Ca-ex-PA, a PSA 'ghost' was identified and the malignant element was either undifferentiated carcinoma or adenocarcinoma. Immunohistochemical staining and evaluation for CDKN2A and FHIT in 55 specimens were undertaken.
  
  
  RESULTS
  The results showed positive nuclear expression of p16 and FHIT in normal parotid gland. None (0%) of the PSA cases demonstrated loss of expression of nuclear FHIT, while 6/26 (23.1%) showed loss of FHIT express. Loss of CDKN2A expression was found in 12/29 (41.4%) of PSAs and 8/26 (30.8%) of Ca-ex-PAs. The nuclear expression pattern for FHIT was significantly more frequent in Ca-ex-PAs compared to PSAs (p=0.014).
  
  
  CONCLUSIONS
  Our data suggest that inactivation of tumour suppressor genes plays an important role in the evolution of Ca-ex-PA. Furthermore, alteration of CDKN2A expression was found to be an early event in the malignant transformation of pleomorphic adenoma and could be considered as a target for gene therapy. More interestingly, we found that nuclear FHIT expression could be used as a good marker to distinguish PSA from Ca-ex-PA.
authors: Department of Biomedical Sciences, School of Dentistry, AlFarabi College, Riyadh, Saudi Arabia. omar.kujan@gmail.com
authors: Omar
authors: O
authors: Kujan
authors: Bassel
authors: B
authors: Tarakji
authors: Nalin
authors: N
authors: Thakker
authors: Abdul Aziz
authors: AA
authors: Al Kheraif
authors: Philip
authors: P
authors: Sloan
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016612:Paraffin Embedding; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase