Similarity in expression of cell cycle proteins between in situ and invasive ductal breast lesions of same differentiation grade

There is increasing evidence that there are different progression routes le ading to invasive breast cancer, depending on histology and differentiation grade. The aim of this study was to determine alterations in the expressio n of proteins involved in proliferation and apoptosis in non-invasive and i nvasive ductal breast lesions. Immunohistochemistry was performed on 106 us ual ductal hyperplasias (UDH), 61 DCIS lesions and 53 invasive ductal breas t carcinomas. Increased proliferation (Ki67), overexpression of cyclin D1, HER-linen, pit and p53, and decreased expression of bcl-2 and p27 could alr eady be found in UDH, Significant differences between UDH and DCIS lesions were found for only one protein when UDH was compared with well-differentia ted DCIS (p27), for three proteins when compared with intermediately differ entiated DCIS (p21, cyclin DI, Ki-67), and far all proteins when compared w ith poorly-differentiated DCIS, Comparing DCIS with invasive lesions of sam e differentiation grade, proliferation was elevated in the invasive lesions . Altered expression of the other proteins was in general only slightly inc reased in the invasive lesion compared with DCIS, The number of proteins wi th altered expression per lesion was highest in poorly-differentiated lesio ns and was comparable between DCIS and invasive cancer of the same differen tiation grade. In conclusion, the biggest changes in expression of these pr oliferation and apoptosis related proteins appear to occur during the trans ition from hyperplasia to DCIS; they probably play a minor role in the tran sition from DCIS to invasive breast lesion of same differentiation grade. W ell-differentiated in situ and invasive breast lesions share many of the ab errations in expression of these proteins, as do poorly-differentiated in s itu and invasive lesions. However, there are manly differences between the well and poorly-differentiated lesions. This further supports the existence of different progression routes leading to breast cancer; Copyright (C) 20 01 John Wiley & Sons, Ltd.