Rieger-Christ K M, Pezza J A, Dugan J M, Braasch J W, Hughes K S, Summerhayes I C
Cell and Molecular Biology Laboratory, Robert E Wise Research and Education Institute, Burlington, MA 01805, USA.
Mol Pathol. 2001 Apr;54(2):91-7. doi: 10.1136/mp.54.2.91.
The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients.
Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and beta-catenin were assessed with the use of immunohistochemistry.
Immunohistochemistry revealed a lack of expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma.
These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.
小叶原位癌（LCIS）与浸润性乳腺癌之间的关系尚未明确。为了确定LCIS是否为浸润性癌的前驱病变，对23例患者的LCIS及相关浸润性乳腺癌的突变状态和E-钙黏蛋白表达进行了分析。
从23例患者的组织中分别显微切割出LCIS灶及相关浸润癌灶。采用单链构象多态性（SSCP）分析E-钙黏蛋白基因的第4至16外显子；利用免疫组织化学评估E-钙黏蛋白和β-连环蛋白的蛋白表达及定位。
免疫组织化学显示，大多数LCIS样本和浸润灶中E-钙黏蛋白和β-连环蛋白缺乏表达。除4例患者外，LCIS及相关浸润区域的染色模式均相同。当E-钙黏蛋白缺失时，β-连环蛋白也未检测到，提示这些病变中缺乏其他经典钙黏蛋白成员的表达。在这组患者中未发现LCIS及相关浸润性癌中E-钙黏蛋白的同时突变。然而，对浸润性病变周围多个原位癌灶的E-钙黏蛋白进行突变分析，为支持导管原位癌作为浸润性导管癌的前驱病变提供了证据。
这些数据支持以下假说，即LCIS不是浸润性乳腺癌的前驱病变，而是发生浸润性疾病风险增加的一个标志物。
