Zhu X L, Hartwick W, Rohan T, Kandel R
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Mod Pathol. 1998 Nov;11(11):1082-8.
Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.
细胞周期蛋白D1在调节细胞周期进程中起关键作用。在乳腺癌中已检测到细胞周期蛋白D1的基因扩增和蛋白过表达，但对于这些变化是否发生在正常乳腺组织以及与浸润性乳腺癌发生风险增加相关的乳腺病变中，人们了解甚少。我们通过差异聚合酶链反应（PCR）和免疫组织化学染色，在30例乳腺良性疾病（16例无异型性的上皮增生和14例非典型导管增生）和18例导管原位癌中寻找细胞周期蛋白D1基因扩增和蛋白过表达情况。我们将所得频率与15例正常乳腺组织和17例浸润性导管癌中的频率进行比较。我们发现，正常乳腺组织中有15%出现细胞周期蛋白D1基因扩增，无异型性的上皮增生中有19%，非典型导管增生中有27%，导管原位癌中有35%，浸润性导管癌中有25%；蛋白过表达的相应比例分别为13%、13%、57%、50%和64%。这些结果表明，细胞周期蛋白D1扩增和蛋白过表达可在出现组织学改变之前发生，但这些变化在具有细胞异型性的组织学病变（非典型增生和导管原位癌）中频率更高，达到与浸润性癌中观察到的频率相似的水平。
