Kleer C G, van Golen K L, Braun T, Merajver S D
Department of Pathology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
Mod Pathol. 2001 May;14(5):458-64. doi: 10.1038/modpathol.3880334.
E-cadherin is a transmembrane glycoprotein that mediates epithelial cell-to-cell adhesion. Because loss of E-cadherin expression results in disruption of cellular clusters, it has been postulated that E-cadherin functions as a tumor suppressor protein. The role of E-cadherin in inflammatory breast cancer (IBC), a distinct and highly aggressive form of breast cancer, is largely unknown. The aim of our study was to elucidate whether E-cadherin expression contributes to the development and progression of the IBC phenotype and to investigate any differences in E-cadherin expression between IBC and stage-matched non-IBC. Forty-two breast cancer cases (20 IBC and 22 non-IBC) were identified. Strict and well-accepted criteria were used for the diagnosis of IBC. Clinical and pathologic features were studied, and formalin-fixed, paraffin-embedded tissue sections were immunostained for E-cadherin, estrogen and progesterone receptors (ER and PR, respectively), and HER2/neu. Statistical analysis was performed using Fisher's exact test. All IBC uniformly expressed E-cadherin, whereas 15 of the 22 (68%) of the non-IBC expressed the protein (P = .006). Intralymphatic tumor emboli in the IBC cases were also all E-cadherin positive. Two IBC tumors demonstrated invasive lobular histology, and both cases were positive for E-cadherin. Of the non-IBC cases, three were invasive lobular carcinomas, and all were positive for E-cadherin. No association was found between E-cadherin expression and ER, PR status, or HER2/neu overexpression. Our study demonstrates that there is a strong association between E-cadherin expression and IBC and suggests that E-cadherin may be involved in the pathogenesis of this form of advanced breast cancer. In our study, we demonstrate that circulating IBC tumor cells strongly express E-cadherin, thereby providing an important exception to the positive association between E-cadherin loss and poor prognosis in breast cancer.
E-钙黏蛋白是一种介导上皮细胞间黏附的跨膜糖蛋白。由于E-钙黏蛋白表达缺失会导致细胞簇的破坏，因此推测E-钙黏蛋白作为一种肿瘤抑制蛋白发挥作用。E-钙黏蛋白在炎性乳腺癌（IBC）（一种独特且侵袭性很强的乳腺癌形式）中的作用在很大程度上尚不清楚。我们研究的目的是阐明E-钙黏蛋白表达是否有助于IBC表型的发生和进展，并研究IBC与分期匹配的非IBC之间E-钙黏蛋白表达的任何差异。确定了42例乳腺癌病例（20例IBC和22例非IBC）。采用严格且被广泛接受的标准诊断IBC。研究了临床和病理特征，并用福尔马林固定、石蜡包埋的组织切片对E-钙黏蛋白、雌激素和孕激素受体（分别为ER和PR）以及HER2/neu进行免疫染色。使用Fisher精确检验进行统计分析。所有IBC均一致表达E-钙黏蛋白，而22例非IBC中有15例（68%）表达该蛋白（P = 0.006）。IBC病例中的淋巴管内肿瘤栓子也均为E-钙黏蛋白阳性。2例IBC肿瘤表现为浸润性小叶组织学，且两例均为E-钙黏蛋白阳性。在非IBC病例中，3例为浸润性小叶癌，且均为E-钙黏蛋白阳性。未发现E-钙黏蛋白表达与ER、PR状态或HER2/neu过表达之间存在关联。我们的研究表明E-钙黏蛋白表达与IBC之间存在密切关联，并提示E-钙黏蛋白可能参与这种晚期乳腺癌形式的发病机制。在我们的研究中，我们证明循环中的IBC肿瘤细胞强烈表达E-钙黏蛋白，从而为E-钙黏蛋白缺失与乳腺癌预后不良之间的正相关提供了一个重要的例外情况。
