title: FHIT (fragile histidine triad) gene analysis in cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  Recently a candidate tumor suppressor gene, FHIT (fragile histidine triad), was identified at chromosome 3p14.2. Abnormality of this gene has been observed in a variety of human tumors. Although aberrant FHIT transcripts in a substantial percentage of cervical cancer cell lines and primary cervical tumors were also noted, some other studies revealed different results. Therefore, its association with the development of cervical cancer is still debatable. Because allelic loss in chromosome 3p is also a frequent finding in cervical intraepithelial neoplasia (CIN), we compared the transcription pattern and expression of FHIT in the preinvasive cervical lesions and normal cervical epithelia to investigate its possible role in cervical carcinogenesis.
  
  
  METHODS
  Thirty-five consecutive CIN lesions taken from conization specimens and 33 normal cervical epithelial tissues taken from hysterectomy for benign diseases were included in this study. Total RNA was extracted from the pathology-confirmed tissue samples and first-strand cDNA was synthesized. It was amplified using a nested reverse transcription polymerase chain reaction (RT-PCR) method. The PCR products were then subjected to subcloned sequence analysis. Paraffin blocks from all of the samples were selected and prepared for immunohistochemical study with an anti-FHIT polyclonal antibody.
  
  
  RESULTS
  All the cDNAs of CIN and normal cervical epithelial tissues showed the expected size of RT-PCR product. However, 7 of the 35 (20%) CIN lesions and 5 of the 33 (15%) normal cervical epithelia also presented aberrant transcripts in addition to the normal-sized transcript of FHIT. Deletion of the cDNA segment covering exon 4 to exon 8 was the most frequent finding in the cases that showed abnormal FHIT transcripts. FHIT protein was intermediately or strongly expressed in most of the CIN lesions and normal squamous epithelia. However, reduced or absent FHIT expression was observed heterogeneously in the 7 CIN lesions and 5 normal cervices in which aberrant FHIT transcripts were detected.
  
  
  CONCLUSIONS
  Because the normal-sized FHIT transcript was present robustly in all of the CIN lesions and the abnormal FHIT transcripts occurred with similar frequency and pattern in the CIN lesions and normal cervical tissues, we suggest that abnormal FHIT transcription might not be causal in the early process of cervical carcinogenesis.
authors.affiliation: Division of Gynecologic Oncology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China. fsliu@vghtc.vghtc.gov.tw
authors.forename: F S
authors.initials: FS
authors.lastname: Liu
authors.forename: Y T
authors.initials: YT
authors.lastname: Hsieh
authors.forename: J T
authors.initials: JT
authors.lastname: Chen
authors.forename: E S
authors.initials: ES
authors.lastname: Ho
authors.forename: M J
authors.initials: MJ
authors.lastname: Hung
authors.forename: A J
authors.initials: AJ
authors.lastname: Lin
mesh_terms: D017766:Acid Anhydride Hydrolases; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase