De Leeuw W J, Berx G, Vos C B, Peterse J L, Van de Vijver M J, Litvinov S, Van Roy F, Cornelisse C J, Cleton-Jansen A M
Department of Pathology, Leiden University Medical Center, The Netherlands.
J Pathol. 1997 Dec;183(4):404-11. doi: 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.
Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and gamma-catenin, were studied in a series of 38 lobular breast carcinomas with known E-cadherin mutation status. The effect of loss of E-cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane-associated E-cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non-sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E-cadherin and alpha- and beta-catenin expression was found; in 50 per cent of these cases, additional loss of gamma-catenin was observed. In six invasive lobular carcinomas, expression of both E-cadherin and catenins was retained. In none of these carcinomas was an E-cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E-cadherin and catenins in all the cases studied--remarkably, also, in four cases positive for E-cadherin and catenin expression in the invasive component. These results indicate that simultaneous loss of E-cadherin and alpha-, beta- and gamma-catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer. Events additional to E-cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma.
由于突变失活，细胞间粘附分子E-钙粘蛋白的表达缺失在浸润性小叶乳腺癌中经常出现。在一系列38例已知E-钙粘蛋白突变状态的小叶乳腺癌中，研究了E-钙粘蛋白以及构成粘着连接细胞质复合体的分子α-、β-和γ-连环蛋白的表达模式。研究了E-钙粘蛋白因突变失活（或其他机制）而缺失对连环蛋白表达的影响。在38例浸润性小叶癌中，有32例观察到质膜相关E-钙粘蛋白表达完全缺失，其中21例在E-钙粘蛋白的细胞外结构域发现了突变。总共鉴定出15个小缺失或插入的移码突变，范围从1到41bp，3个无义突变和3个剪接突变。突变分布在整个编码区域，未检测到热点。在所有病例中，均发现E-钙粘蛋白以及α-和β-连环蛋白表达同时缺失；在其中50%的病例中，还观察到γ-连环蛋白额外缺失。在6例浸润性小叶癌中，E-钙粘蛋白和连环蛋白的表达均得以保留。在这些癌中均未检测到E-钙粘蛋白突变。与浸润性小叶癌相邻的小叶原位癌在所有研究病例中均显示E-钙粘蛋白和连环蛋白同时缺失——值得注意的是，在浸润成分中E-钙粘蛋白和连环蛋白表达呈阳性的4例病例中也是如此。这些结果表明，E-钙粘蛋白以及α-、β-和γ-连环蛋白的同时缺失可能是小叶原位癌形成过程中的一个重要步骤，而小叶原位癌是浸润性小叶乳腺癌的前体。E-钙粘蛋白失活之外的其他事件必定参与了小叶原位癌向浸润性小叶癌的转变。
