乳腺外周型乳头状瘤及其癌变细胞的克隆性研究  

Clonality of the peripheral papilloma and cancerous cells of breast

作　　者：牛昀[1] 于琦[1] 于泳[1] 丁秀敏[1] 史玉荣[1] 

机构地区：[1]天津医科大学肿瘤医院国家(教育部)乳腺癌防治重点实验室,300060

出　　处：《中华医学杂志》2007年第8期542-545,共4页National Medical Journal of China

基　　金：天津市科委自然科学基金(033611911)

摘　　要：目的探讨乳腺外周性乳头状瘤及其癌变细胞和导管内癌的克隆性,寻找较为特异性有效的早期诊断辅助性方法。方法收集外周型乳头状瘤26例、外周型乳头状瘤伴不典型增生25例、导管内癌27例、癌变至导管内癌的16例作为研究对象,并用20例正常乳腺组织作对照,采用基于女性 X 染色体 AR 基因多态性的克隆性分析技术检测,根据带型不同判断各种样本的克隆性。结果 26例外周型乳头状瘤中24例(92.3%)和20例正常乳腺组织显示为多克隆性增生;27例导管内癌均显示单克隆性增生;在25例外周型乳头状瘤伴不典型增生样本中10例(40%)显示 AR 位点长度多态性丢失,属于单克隆性增生;16例癌变至导管内癌标本中癌灶与伴不典型增生部分均显示单克隆性增生。结论正常乳腺组织和外周型乳头状瘤具有多克隆性,而伴不典型增生的外周型乳头状瘤部分病例为单克隆性增生。外周型乳头状瘤伴不典型增生属于乳腺癌前病变。克隆性分析可有助于筛选高危病例及鉴别诊断。Objective To study the clonality status of peripheral papilloma （peri-MP）, ductal carcinoma in situ （ DCIS）, and normal tissue of the breast using an assay based on inactivation mosaicism of the length-polymorphic X-chromosomes at the androgen receptor （AR） locus and to explore a reliable way to distinguish the benign and malignant （or pre-malignant ） cases judged morphologically. Methods Specimens of breast tissues were obtained from 26 cases of peri-PM, 25 cases of peri-PM with atypical ductal hyperplasia （ADH）, and 27 cases pf DCIS, 16 cases of developed canceration, and 20 normal women. DNA was extracted and amplified via nested-PCR with or without previous digestion by the methylationsensitive restriction endonuclease Hha I. The products were resolved on denaturing polyacrylamide gels and visualized through silver staining. The clonality of these samples was analyzed by showing the lanes. Results Loss of polymorphism at the AR locus was found in all the cases with DCIS and in 10 cases （10/25, 40. 0% ） of peri-PM with ADH, indicating the monoclonality of the tumor. Twenty-four cases （92.3%） of the 26 cases with peri-PM and the 20 specimens of normal tissue were shown to be polyclonal. In the 16 cases of developed canceration identical X chromosome inactivation （monoclonal alterations） was observed in the cancer focus, parts of peri-PM with ADH, and the part of DCIS. Conclusion Normal breast tissue and peri-PM show polyclonalty and the peri-PM with ADH shows monoclonality. Clonality analysis may be a useful modality to screen high-risk cases from precancerous lesions or to distinguish between the benign hyperplasia and early carcinoma.

关 键 词：乳腺外周型乳头状瘤 癌前病变 导管内癌 克隆性分析 AR基因 

分 类 号：R737.9[医药卫生—肿瘤]