DNA topoisomerase II-alpha expression in duct hyperplasia and in situ ductcarcinoma of the breast: Correlation with histologic classification of in situ duct carcinoma

Proliferative lesions of the breast include both ductal hyperplasias and du ctal carcinoma in situ (DCIS). It is becoming apparent that this group of l esions is heterogeneous both in clinical behavior and morphologic pattern. Separation of ductal hyperplasia from in situ ductal cancer is based on mor phologic features. Lesions of DCIS were recently grouped into low, intermed iate, and high-grade categories based on morphologic features of nuclear cy tology, necrosis, and architecture. Although it is generally agreed that mi totic activity is greater in high-grade lesions than in low-grade ones, pro liferation measurements were not included in the newer classification schem es of DCIS, DNA topoisomerase II-alpha (topo II-alpha) is well-characterized molecule t hat was recently shown to be a marker of cell proliferation in invasive bre ast cancer. An antibody against the protein recognizes the enzyme in paraff in-embedded human tissue sections and can be used to estimate the fraction of cycling cells in both normal and tumor tissue. In this study, we stained for topo II-alpha 38 proliferative lesions of the breast in which the diag noses ranged from ductal hyperplasia to high-grade DCIS, The average topo I I-alpha index in ductal hyper plasias was 1.64 +/- 1.1 (n = 13); in low-gra de DCIS, 6.06 +/- 6.3 (n = 7); in intermediate-grade DCIS, 13.55 +/- 7.7 (n = 10); and in high-grade DCIS, 34.1 +/- 12.3 (n = 8). The incorporation of cell proliferation into the grading of proliferative breast lesions can be readily accomplished by immunohistochemical staining for topo II-alpha, an d in this report we demonstrate that this technique can be performed reliab ly and quickly in a routine pathology practice by standard light microscopy .