Cyclin D-1 gene amplification and overexpression are present in ductal carcinoma in situ of the breast

Cyclin D1 (CCND1) amplification is found in 10-15 per cent of invasive brea st carcinomas, but it is not web established whether this gene alteration a lso occurs in the precursor of invasive breast carcinoma, ductal carcinoma in situ (DCIS), By Southern blot analysis, cyclin D1 gene amplification was detected in 10 per cent (3/32) of DCIS cases. In addition, 15 cases of DCI S were analysed using bright field in situ hybridization (BRISH), of which 11 had already been analysed by Southern blotting, One additional case with gene amplification was found by BRISH. The use of BRISH for the detection of gene amplification is shown to be a novel and reliable in situ method on paraffin-embedded tissue sections. By immunohistochemistry, 147 cases of D CIS mere analysed for the expression of cyclin D1, Cyclin D1 overexpression was found in 9 per cent of well-differentiated, 29 per cent of intermediat ely differentiated, and 19 per cent of poorly differentiated DCIS, No stati stically significant association was found between cyclin D1 overexpression and the differentiation grade of DCIS, although 90 per cent of the cases t hat show overexpression are classified as intermediately and poorly differe ntiated, An association was found between cyclin D1 overexpression and oest rogen receptor positivity, Cyclin D1 overexpression was found in all four c ases with cyclin D1 gene amplification, but was also found in 30 per cent ( 8/27) of cases without detectable gene amplification, It is concluded that cyclin D1 gene amplification is an early event in the development of breast carcinoma and occurs in poorly differentiated DCIS, Cyclin D1 protein over expression is also present in tumours without cyclin D1 gene amplification and is seen predominantly in DCIS of intermediately and poorly differentiat ed histological type and oestrogen receptor positivity, Copyright (C) 1999 John Wiley & Sons, Ltd.