5'-CpG island methylation of the FHIT gene is associated with reduced protein expression and higher clinical stage in cervical carcinomas

Ultrastruct Pathol. 2003 Nov-Dec;27(6):417-22. doi: 10.1080/01913120390250329.

Abstract

Aberrant transcription of the FHIT gene has been observed in many solid tumors, suggesting that 5'-CpG island methylation of the FHIT gene is involved in tumor development. The authors investigated the status of the 5'-CpG island methylation of the FHIT gene and protein expression in a series of 40 cervical carcinomas and 10 normal cervical epithelial samples, and correlated the data with clinicopathological findings. Methylation-specific PCR was applied to detect the incidence of the 5'-CpG island methylation, and immunohistochemistry was used for FHIT protein staining. 5'-CpG island methylation of the FHIT gene was detected in 40% (16/40) of the cervical cancer samples and in none of normal cervical epithelial specimens. Furthermore, the 5'-CpG island methylation was positively associated with clinical stage (p=.002). All the normal cervical epithelial samples (10/10) and 90% (36/40) of the cervical carcinomas were positive when the unmethylated primer pair was applied. Of the 16 cervical carcinomas with 5'-CpG island methylation of the FHIT gene by PCR, 15 showed reduced FHIT protein expression. This study suggests that 5'-CpG island methylation plays an important role in inactivation of the FHIT gene in cervical cancer.

MeSH terms

  • Acid Anhydride Hydrolases / biosynthesis*
  • Acid Anhydride Hydrolases / genetics
  • Adult
  • Aged
  • CpG Islands / genetics*
  • DNA Methylation*
  • Female
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Neoplasm Proteins
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases