中文摘要：

目的肿瘤抑制基因p53突变是浸润性乳腺癌发生发展中常见事件,而其与包括普通型增生（UDH）,不典型增生（ADH）及导管内原位癌（DCIS）的乳腺导管内增生性病变关系不明。探讨p53在乳腺导管内增生性病变的外显子突变情况,以期了解p53突变在乳腺癌发生发展中的作用。方法用高分辨率熔解曲线和测序研究122例乳腺导管内增生性病变中p53外显子5～8的突变情况。结果经HRM筛选,14例患者DNA熔解曲线与野生型标准品熔解曲线大于阈值,经测序分析,其中13例出现p53外显子突变。35例UDH中均未发现突变,10.7%（6/56）ADH和22.6%（7/31）DCIS发现至少1个位点的点突变,其中1例DCIS发现2个位点的突变。结论 p53突变发生于乳腺导管内增生性病变中的ADH与DCIS,其可能为乳腺癌发生发展中的早期事件。

英文摘要：

Objective Although p53 mutation is one of the most common alterations identified in invasive breast carcinomas,it is not clear whether its alteration frequently occurs in intraductal proliferative lesions including usual ductal hyperplasia （UDH）,atypical ductal hyperplasia （ADH） and ductal carcinoma in situ （DCIS）.The aim of this study is to investigate the p53 mutation in intraductal proliferative lesions,and clarify its significance in breast carcinogenesis.Methods p53 mutation was examined in 122 cases of noninvasive breast lesions including UDH,ADH and DCIS by high-resolution melting （HRM）,followed by DNA sequence.Results The positive rates of p53 mutation were 0.0%,10.7% and 22.6% in UDH,ADH and DCIS,respectively.Conclusion p53 mutation occurs in intraductal proliferative lesions including ADH and DCIS,and might be an early event in breast carcinogenesis.