Hidaka N, Nagao T, Asoh A, Kondo Y, Nagao K
Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara, Chiba, Japan.
Mod Pathol. 1998 Nov;11(11):1039-45.
Bronchioloalveolar carcinoma (BAC) has features distinct from those of conventional pulmonary adenocarcinoma (CPA) in terms of its characteristic growth pattern along alveolar walls and intrapulmonary metastasis via the aerogenous route. We speculated, therefore, that BAC might differ from CPA in its capacity for cell-to-cell or cell-to-basement membrane adhesion. E-cadherin (E-CD), one of the most important elements of epithelial integrity molecules, is related to tumor metastasis in various organs. Differences of E-CD and associated catenin expressions between BAC and CPA, however, have not been elucidated. We examined the expression of E-CD and alpha-, beta- and gamma-catenin immunohistochemically in 18 BACs (9 mucinous, 7 nonmucinous, and 2 sclerosing) in comparison with CPAs, all of which were well-differentiated adenocarcinomas. In addition, we analyzed the correlation between the expression of these cell adhesion molecules and the presence of intrapulmonary metastasis, histologic subtypes, and cell proliferation activity. Clinicopathologically, we observed intrapulmonary metastases in 4 of the 18 BACs and none of the CPAs. In 14 of the 18 BACs, more than one-half of the tumor cells expressed E-CD, and the E-CD expression level was significantly higher in the BACs than in the CPAs. In addition, all of the BACs exhibited preserved membranous staining for E-CD, whereas in 5 of the 14 CPAs, the expression pattern was disorganized cytoplasmic staining; the difference was statistically significant. The Ki-67 labeling index was significantly lower in the BACs than in the CPAs. There were no appreciable differences in E-CD expression among the BAC subtypes. E-CD expression was significantly lower in the BACs with intrapulmonary metastasis than in the BACs without intrapulmonary metastasis. These findings indicated to us that BAC was distinct from CPA in terms of proliferation activity and expression of certain adhesion molecules and that E-CD downregulation was associated with a tendency toward intrapulmonary metastasis.
细支气管肺泡癌（BAC）在其沿肺泡壁的特征性生长模式以及通过气源性途径的肺内转移方面，具有与传统肺腺癌（CPA）不同的特征。因此，我们推测BAC在细胞间或细胞与基底膜黏附能力方面可能与CPA不同。E-钙黏蛋白（E-CD）是上皮完整性分子的最重要成分之一，与多种器官的肿瘤转移有关。然而，BAC和CPA之间E-CD及相关连环蛋白表达的差异尚未阐明。我们采用免疫组织化学方法检测了18例BAC（9例黏液性、7例非黏液性和2例硬化性）中E-CD以及α-、β-和γ-连环蛋白的表达，并与CPA进行比较，所有CPA均为高分化腺癌。此外，我们分析了这些细胞黏附分子的表达与肺内转移的存在、组织学亚型以及细胞增殖活性之间的相关性。临床病理方面，我们在18例BAC中有4例观察到肺内转移，而CPA中无一例发生肺内转移。在18例BAC中的14例中，超过一半的肿瘤细胞表达E-CD，且BAC中E-CD的表达水平显著高于CPA。此外，所有BAC均表现出E-CD的膜性染色保存完好，而在14例CPA中的5例中，表达模式为杂乱的细胞质染色；差异具有统计学意义。BAC中的Ki-67标记指数显著低于CPA。BAC各亚型之间E-CD表达无明显差异。有肺内转移的BAC中E-CD表达显著低于无肺内转移的BAC。这些发现向我们表明，BAC在增殖活性和某些黏附分子的表达方面与CPA不同，且E-CD下调与肺内转移倾向相关。
