Topoisomerase IIα expression in ductal carcinoma in situ of the breast: A preliminary study

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIα (Topo IIα) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIα and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIα was consistently negative in normal ductal epithelium. Topo IIα—labeling index (Topo IIα-LI) was 0.7 ± 0.6% for grade I, 4.3 ± 3.9% for grade II, and 13.4 ± 8.9 for grade III lesions (P < .01). For mixed nuclear grade DCIS, Topo IIα-LI was 6.8 ± 4.8. There was no difference in Topo IIα-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIα-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIα-LI was significantly higher in c-erbB-2—positive lesions (Topo IIα-LI- 12.4 ± 8.5) as compared with negative lesions (Topo IIα-LI- 3.9 ± 4.5, P < .0001). Overexpression of c-erbB-2 and Topo IIα is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions. HUM PATHOL 31:1249-1254.