AMPLIFICATION OF CCND1 AND EXPRESSION OF ITS PROTEIN PRODUCT, CYCLIN D1, IN DUCTAL CARCINOMA IN-SITU OF THE BREAST

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disea se clinically and biologically. The few available studies of its natur al history implicate DCIS as a non-obligate precursor for invasive car cinoma. We have used fluorescence in situ hybridization (FISH) to dete ct gene amplification of the cell cycle regulator gene CCND1 in 88 exa mples of formalin-fixed, paraffin-embedded DCIS. Expression of its pro tein product cyclin D1 was detected by immunohistochemistry. CCND1 was amplified in 18% of DCIS cases. High grade DCIS was more likely to sh ow amplification than low grade DCIS (32% versus 8%; P = 0.08). Gene a mplification was associated with cyclin D1 protein expression (P = 0.0 01), although cyclin D1 was detected in cases that did not demonstrate gene amplification. Overall, cyclin D1 protein was detected in 50% of DCIS cases. Although only 2 of 23 (8%) cases of low grade DCIS had CC ND1 amplification, over 50% (13/23) of these cases expressed cyclin D1 protein. Low grade DCIS had a higher mean percentage of nuclei expres sing cyclin D1 than did intermediate or high grade DCIS (P = 0.007). M echanisms other than gene amplification may be responsible for increas ed cyclin D1 protein in DCIS, especially in low grade DCIS. Identifyin g mechanisms that control cell cycle progression in DCIS may yield clu es to its biological behaviour.