Davidson B, Berner A, Nesland J M, Risberg B, Berner H S, Tropè C G, Kristensen G B, Bryne M, Ann Florenes V
Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway.
J Pathol. 2000 Dec;192(4):460-9. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH726>3.0.CO;2-M.
The aims of this study were firstly, to investigate the expression of E-cadherin complex proteins in ovarian carcinoma cells in serous effusions and in primary and metastatic lesions; and secondly to study the value of these four proteins and calretinin, a mesothelial marker, in the differential diagnosis of ovarian carcinoma cells from reactive mesothelial cells in effusions. Sixty-seven malignant effusions and 97 corresponding primary (n=36) and metastatic (n=61) lesions were immunohistochemically stained for E-cadherin and alpha-, beta-, and gamma-catenin. Staining extent and intensity were scored. Effusion specimens were additionally analysed for calretinin immunoreactivity. Membrane immunoreactivity for E-cadherin and alpha-, beta-, and gamma-catenin was detected on carcinoma cells in the majority of the effusions, but rarely on reactive mesothelial cells (p<0.001 for all markers). Calretinin immunoreactivity was confined to mesothelial cells (p<0.001). An association was seen between E-cadherin and alpha-catenin expression, in both effusions and solid tumours, and for beta-catenin in solid tumours (range p<0. 001 to p=0.014). Up-regulation of all four cadherin complex proteins was seen in carcinoma cells in effusions, when compared with corresponding primary tumours (range p<0.001 to p=0.028). As with effusions, metastatic lesions showed up-regulation of alpha-, beta-, and gamma-catenin when compared with primary carcinomas (p=0.002-0. 015). Carcinoma cells in effusions showed in addition elevated levels of E-cadherin when compared with metastatic lesions (p<0.001). Staining results in effusions showed no association with effusion site, tumour type or histological grade. Immunoblotting on 29 malignant effusions confirmed the presence of all four proteins in the majority of samples and co-precipitation of E-cadherin and beta-catenin was seen in ten specimens examined. E-cadherin complex proteins are widely expressed in ovarian carcinoma cells. Together with calretinin, they form a powerful battery of markers for the cytological diagnosis of carcinoma cells in effusions. The up-regulation of E-cadherin complex proteins in serous effusions and metastatic lesions may mark an early metastatic phenotype and possibly mediates survival of tumour cells at these sites through the inhibition of apoptosis.
本研究的目的，其一，是调查E-钙黏蛋白复合蛋白在浆液性积液中的卵巢癌细胞以及原发性和转移性病变中的表达情况；其二，是研究这四种蛋白以及间皮标志物钙视网膜蛋白在鉴别诊断积液中的卵巢癌细胞与反应性间皮细胞中的价值。对67例恶性积液以及97例相应的原发性（n = 36）和转移性（n = 61）病变进行免疫组织化学染色，检测E-钙黏蛋白、α-连环蛋白、β-连环蛋白和γ-连环蛋白。对染色范围和强度进行评分。另外，对积液标本进行钙视网膜蛋白免疫反应性分析。在大多数积液的癌细胞上检测到E-钙黏蛋白、α-连环蛋白、β-连环蛋白和γ-连环蛋白的膜免疫反应性，但在反应性间皮细胞上很少见（所有标志物p < 0.001）。钙视网膜蛋白免疫反应性仅限于间皮细胞（p < 0.001）。在积液和实体瘤中均观察到E-钙黏蛋白与α-连环蛋白表达之间存在关联，在实体瘤中β-连环蛋白也存在关联（范围为p < 0.001至p = 0.014）。与相应的原发性肿瘤相比，积液中的癌细胞中所有四种钙黏蛋白复合蛋白均上调（范围为p < 0.001至p = 0.028）。与积液情况类似，与原发性癌相比，转移性病变中α-连环蛋白、β-连环蛋白和γ-连环蛋白上调（p = 0.002 - 0.015）。与转移性病变相比，积液中的癌细胞中E-钙黏蛋白水平也升高（p < 0.001）。积液中的染色结果与积液部位、肿瘤类型或组织学分级无关。对29例恶性积液进行免疫印迹分析，证实大多数样本中存在所有四种蛋白，在检测的10个标本中观察到E-钙黏蛋白和β-连环蛋白的共沉淀。E-钙黏蛋白复合蛋白在卵巢癌细胞中广泛表达。它们与钙视网膜蛋白一起，构成了用于积液中癌细胞细胞学诊断的强大标志物组合。浆液性积液和转移性病变中E-钙黏蛋白复合蛋白的上调可能标志着早期转移表型，并可能通过抑制凋亡介导肿瘤细胞在这些部位的存活。
