Loss of FHIT protein expression is a marker of adverse evolution in good prognosis localized breast cancer

Int J Cancer. 2003 Dec 10;107(5):854-62. doi: 10.1002/ijc.11462.


The FHIT tumor suppressor gene, which encompasses the fragile site FRA3B at 3p14.2, is altered frequently in many types of human cancers. To determine its importance as a prognostic marker in breast cancer, the expression of the FHIT protein was studied in a series of 452 breast carcinomas by using immunohistochemistry on sections of tissue microarrays. Three distinct levels of FHIT expression were observed: in 154 cases (34.1%) expression was unchanged as compared to normal level; in 78 (17.2%) no expression was found; in the remaining 220 cases (48.7%), expression was intermediate. Overall, two-thirds of the cases had abnormal levels of the protein. Absence of FHIT was significantly associated with a higher grade (p < 0.01) and absence of hormone receptors (p < 0.001). The patients were separated into Group I (153 node-negative good prognosis patients who did not receive adjuvant chemotherapy) and Group II (226 high-risk patients treated by adjuvant chemotherapy) according to the St.-Gallen conference consensus. The median follow-up was 48 months. Among Group I but not Group II patients, a multivariate analysis showed that FHIT expression was significantly associated with disease-free survival. The relative risk of recurrence for FHIT-negative Group I patients was 2.37 (1.21-4.64; p = 0.03). Thus, among the patients who present with tumors of apparent good prognosis, FHIT is an independent prognostic factor that distinguishes a subgroup of patients who could benefit from adjuvant treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases*
  • Adult
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Female
  • Gene Deletion*
  • Genes, Tumor Suppressor*
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Reproducibility of Results
  • Survival Analysis
  • Time Factors


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases