INCREASED PROLIFERATIVE ACTIVITY AND P53 EXPRESSION IN NORMAL GLANDULAR BREAST-TISSUE AFTER RADIATION-THERAPY

Radiation used in breast-conserving therapy (BCT). for early breast ca ncer, to eradicate residual malignant cells after tumour resection, in duces DNA damage and cell death. Little is known about the effect of t he commonly used doses of radiation therapy on normal breast tissue. U nder physiological conditions, p53 plays a role in maintaining genomic stability and regulating progression through the cell cycle. In norma l glandular breast tissue, p53 expression is very low, as is prolifera tive activity. The purpose of this study was to investigate the levels of p53 expression and proliferative activity in non-malignant glandul ar epithelium of the breast after BCT. The immunohistochemical express ion of p53 and Ki-67 was semiquantitatively correlated in non-malignan t glandular epithelium in biopsies before and after BCT in 24 women wi th breast cancer. In 18 cases, a recurrence was diagnosed and in the r emaining cases, the clinical suspicion was not histologically confirme d. In addition, in six cases with contralateral breast cancer, the sam e immunohistochemical evaluation was performed in tissue from both bre asts. The mean interval between the two surgical interventions was 50 months. The percentage of p53 immunoreactive epithelial cells in norma l breast tissue was significantly (P<0.01) higher after radiation ther apy than before in the ipsilateral side (0.2 per cent +/- 0.3 and 4.6 per cent +/- 4.5, respectively). Ki-67 immunoreactivity was also signi ficantly increased (P<0.001) after radiation therapy, from 0.6 per cen t to an average of 4.8 per cent in epithelial cells. In contrast, in t he patients with contralateral breast cancer, the levels of p53 and Ki -67 immunoreactivity in the normal glandular breast tissue were compar able to the ipsilateral side (P=0.7 and P=0.1, respectively). In concl usion, increased expression of p53 and Ki-67 is present in normal glan dular breast tissue, even 2-5 years after radiation therapy. (C) 1998 John Wiley & Sons, Ltd.