The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma.
BACKGROUND
The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma.


METHODS
In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods.


RESULTS
Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors.


CONCLUSIONS
These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas.
Gatalica
Z
Z
Department of Pathology, John Sealy Hospital, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Lele
S M
SM
Rampy
B A
BA
Norris
B A
BA
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002278:Carcinoma in Situ / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D016009:Chi-Square Distribution; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008408:Mastectomy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase