Expression of proliferation and apoptosis-related proteins in usual ductalhyperplasia of the breast

Expression of proliferation- and apoptosis-related proteins was studied by immunohistochemistry in 130 usual ductal hyperplasias of the breast, of whi ch 39 cases (30%) had adjacent invasive cancer. Overexpression of cyclin D1 and Ki-67 was found in 6% and 29% of the cases, respectively. Only two mil d ductal hyperplasias were Her-2/neu positive. Overexpression of p21 and re duced expression of p27, both cdk-inhibitors, was seen in 16% and 27% of th e lesions, respectively. Reduced expression of bcl-2 was found in 16% of th e cases, and p53 accumulation was present in 8%. Expression of six of the s even studied proteins showed no significant difference between mild, modera te, or florid ductal hyperplasias, indicating that there are no important c ell biological differences with regard to the studied proteins between the lesions within this morphologically continuous spectrum. In addition, there were no differences between lesions with and without an invasive component . Cyclin D1 positivity was exclusively seen in lesions with 75% or more p27 -positive nuclei. No significant correlations were found between other prot eins. Twenty-three of 91 lesions (25%) had multiple events, of which five s howed altered expressions of three or four proteins. In conclusion, altered protein expression of several proliferation- and apoptosis-related genes t hat are known to be involved in invasive breast cancer also may be found in usual ductal hyperplastic lesions, including several lesions with multiple events. This implies that usual ductal hyperplastic lesions may be among t he earliest lesions within the breast oncogenetic spectrum. HUM PATHOL 29:1 539-1545. Copyright (C) 1998 by W.B. Saunders Company.