title: Loss of FHIT protein expression is a marker of adverse evolution in good prognosis localized breast cancer.
abstract: 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.
authors.affiliation: Département d'Oncologie Moléculaire, Institut Paoli-Calmettes and U119 INSERM, IFR57, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Valérie-Jeanne
authors.initials: VJ
authors.lastname: Bardou
authors.forename: Cornel
authors.initials: C
authors.lastname: Popovici
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Jeannine
authors.initials: J
authors.lastname: Geneix
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Jacques
authors.initials: J
authors.lastname: Hassoun
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D013997:Time Factors; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase