Mommers E C, van Diest P J, Leonhart A M, Meijer C J, Baak J P
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Hum Pathol. 1998 Dec;29(12):1539-45. doi: 10.1016/s0046-8177(98)90028-4.
Expression of proliferation- and apoptosis-related proteins was studied by immunohistochemistry in 130 usual ductal hyperplasias of the breast, of which 39 cases (30%) had adjacent invasive cancer. Overexpression of cyclin D1 and Ki-67 was found in 6% and 29% of the cases, respectively. Only two mild ductal hyperplasias were Her-2/neu positive. Overexpression of p21 and reduced expression of p27, both cdk-inhibitors, was seen in 16% and 27% of the lesions, respectively. Reduced expression of bcl-2 was found in 16% of the cases, and p53 accumulation was present in 8%. Expression of six of the seven studied proteins showed no significant difference between mild, moderate, or florid ductal hyperplasias, indicating that there are no important cell biological differences with regard to the studied proteins between the lesions within this morphologically continuous spectrum. In addition, there were no differences between lesions with and without an invasive component. Cyclin D1 positivity was exclusively seen in lesions with 75% or more p27-positive nuclei. No significant correlations were found between other proteins. Twenty-three of 91 lesions (25%) had multiple events, of which five showed altered expressions of three or four proteins. In conclusion, altered protein expression of several proliferation- and apoptosis-related genes that are known to be involved in invasive breast cancer also may be found in usual ductal hyperplastic lesions, including several lesions with multiple events. This implies that usual ductal hyperplastic lesions may be among the earliest lesions within the breast oncogenetic spectrum.
通过免疫组织化学方法研究了130例乳腺普通导管增生中增殖和凋亡相关蛋白的表达情况，其中39例（30%）伴有相邻浸润性癌。分别在6%和29%的病例中发现细胞周期蛋白D1和Ki-67过表达。仅有两例轻度导管增生为Her-2/neu阳性。分别在16%和27%的病变中观察到细胞周期蛋白依赖性激酶抑制剂p21过表达和p27表达降低。16%的病例中发现bcl-2表达降低，8%的病例中存在p53积聚。所研究的七种蛋白中的六种在轻度、中度或旺炽性导管增生之间未显示出显著差异，表明在这个形态学连续谱系内的病变之间，在所研究的蛋白方面不存在重要的细胞生物学差异。此外，有浸润成分和无浸润成分的病变之间也没有差异。细胞周期蛋白D1阳性仅见于p27阳性核占75%或更多的病变中。其他蛋白之间未发现显著相关性。91个病变中有23个（25%）存在多种异常情况，其中5个显示三种或四种蛋白表达改变。总之，在乳腺普通导管增生性病变中，包括一些存在多种异常情况的病变，也可能发现几种已知与浸润性乳腺癌相关的增殖和凋亡相关基因的蛋白表达改变。这意味着乳腺普通导管增生性病变可能是乳腺肿瘤发生谱系中最早的病变之一。
