Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N−/C−) and 72 (24%) cases showed expression of only the C-terminus (N−/C+). In all cases, the expression of p120-catenin and β-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N−/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N−/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.

乳腺浸润性小叶癌（ILC）的特点是肿瘤细胞的不粘性生长，这主要与E-钙粘蛋白（E-cad）表达完全丧失有关。然而，ILC 中已报道 E-cad 蛋白的一些异常表达模式与其形态不一致。我们在此报道了表达一种新型异常E-cad蛋白的ILC病例，该蛋白缺乏N端结构域，但在细胞膜上保留了C端结构域。使用针对 E-cad N末端或C 末端区域的特异性抗体对 299 例 ILC 病例进行免疫组织化学染色，结果显示 227 例 (76%) 病例显示两个末端 (N−/C−) 和 72 例 (72%) 的膜表达缺失。 24%) 病例仅显示 C 末端 (N−/C+) 的表达。在所有情况下，p120-catenin 和 β-catenin 的表达与 E-cad C 末端的表达一致。临床病理分析显示，ILC细胞中N−/C+表达与组织学亚型（尤其是混合型ILC与另一种组织学类型）和免疫组化分子亚型（尤其是三阴性亚型）显着相关，但与预后因素（pT）无关。或pN）。此外，E-cad N 端细胞质定位异常的 15 例中有 12 例 (80%) 显示 C端结构域的弥漫性膜表达。使用识别细胞外近膜区域的抗体进行的额外免疫组织化学显示，28 (39%) 的 N-/C+ 病例丢失了膜表达，表明 N 末端区域的缺失模式存在多样性。我们的研究结果为因 ILC 中 E-cad 蛋白 N 末端缺陷而导致 E-cad 功能丧失提供了一种新机制。