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 assessed 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 second retrospective series of 156 consecutive breast carcinomas for the expression of the Fhit protein. In nine (31%) cases of the first series, FHIT transcripts were either aberrant or absent as determined by reverse transcription-PCR, and Fhit protein levels in tumors were low or absent as determined immunohistochemically. In 11 other cases (38%), only normal FHIT transcripts were detected by PCR, paralleled by the reduction or absence of Fhit protein. In the remaining nine cases (31%), the presence of the normal FHIT transcript corresponded to protein levels that were similar in tumor and normal 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 alteration in Fhit expression in breast carcinomas is a frequent event. Analysis of correlation between Fhit expression and pathological, clinical, and biological parameters in these 29 tumors and in a second retrospective series of 156 consecutive primary breast carcinomas indicated that a decrease or an absence of Fhit protein expression is associated with high proliferation and large tumor size.