FHIT loss of function in human primary breast cancer correlates with advanced stage of the disease

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumor suppressor gene involved in different tumor types, We have assesse d 29 human primary breast carcinomas for both the presence of abnormal FHIT transcripts and the Fhit protein levels as compared with the normal breast epithelium of the same patients. In addition, we have also examined a seco nd retrospective series of 156 consecutive breast carcinomas for the expres sion of the Fbit protein. In nine (31%) cases of the first series, FHIT tra nscripts were either aberrant or absent as determined by reverse transcript ion-PCR, and Fhit protein levels in tumors were low or absent as determined immunohistochemically. In 11 other cases (38%), only normal FHIT transcrip ts were detected by PCR, paralleled by the reduction or absence of Fhit pro tein, In the remaining nine eases (31%), the presence of the normal FHIT tr anscript corresponded to protein levels that were similar in tumor and norm al breast epithelia, Thus, alterations in FHIT transcripts were detected in 31% of the patients, but reduction or absence of Fhit protein occurred in 69% of the breast carcinoma samples examined. These data suggest that alter ation in Fhit expression in breast carcinomas is a frequent event. Analysis of correlation between Fhit expression and pathological, clinical, and bio logical parameters in these 29 tumors and in a second retrospective series of 156 consecutive primary breast carcinomas indicated that a decrease or a n absence of Fhit protein expression is associated with high proliferation and large tumor size.