Analysis of the fragile histidine triad (FHIT) gene in lobular breast cancer

The fragile histidine triad (FHIT) gene is a candidate tumour suppressor ge ne in breast and other cancers. We investigated deletions within the FHIT g ene in lobular breast cancer and found that 16% of cases showed loss of het erozygosity (LOH) within the gene. We compared LOH within FHIT in lobular a nd ductal breast tumours and found a significant association between LOH at FHIT and the ductal histological type (P < 0.001). To determine whether ge nomic alteration of the FHIT gene in lobular breast cancer leads to Fhit in activation we have assessed the level of Fhit expression by immunohistochem ical detection and determined that 27% (15 of 55) consecutive sporadic lobu lar tumours showed negative or reduced Fhit expression. A significant assoc iation was found between LOH at the FHIT gene and reduced Fhit expression i n lobular and ductal tumours (P = 0.035 and P = 0.001, respectively). Thus, genetic alterations within the FHIT gene, leading to loss of Fhit protein, may play an important role in the carcinogenesis of a significant number o f sporadic lobular breast cancers, even though the apparent frequency of ge nomic alterations within the gene is lower than in ductal breast cancer. (C ) 2000 Published by Elsevier Science Ltd. All rights reserved.