Gonzalez M A, Pinder S E, Wencyk P M, Bell J A, Elston C W, Nicholson R I, Robertson J F, Blamey R W, Ellis I O
Department of Histopathology, The City Hospital, Nottingham, U.K.
J Pathol. 1999 Apr;187(5):523-9. doi: 10.1002/(SICI)1096-9896(199904)187:5<523::AID-PATH296>3.0.CO;2-3.
This study examines the expression of the cell-cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix-cell adhesion molecules beta1- and alpha2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of alpha- and beta/gamma-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of alpha- and beta/gamma-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p=0.002) and tumour type (p<0.001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. alpha-catenin intensity also showed a relationship with grade (p=0.008) and with oestrogen receptor (ER) status (p=0.006). beta/gamma-catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with beta1- and alpha2-integrin, respectively, and co-ordinated loss of beta1- and alpha2-integrin expression was found. Both beta1- and alpha2-integrin expression were associated with histological grade (p=0.003 and p=0.031, respectively) and beta1 immunoreactivity with tumour type (p=0.010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p=0.087) towards poorer survival of patients with tumours with absent or weak expression of beta1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour.
本研究检测了细胞间黏附分子E-钙黏蛋白及其相关蛋白连环蛋白,以及基质-细胞黏附分子β1-整合素和α2-整合素在原发性浸润性乳腺癌中的表达。通过对55例冰冻切片进行免疫组化,以半定量评分免疫反应强度和比例来评估表达情况。研究了这些分子之间的相互关系,以及它们与其他组织学和预后特征及生存情况的关联。E-钙黏蛋白表达缺失与α-连环蛋白和β/γ-连环蛋白免疫染色缺失之间存在显著关联。20%的病例中,E-钙黏蛋白抗体的膜免疫反应性缺失。分别有24%和22%的乳腺癌病例中观察到α-连环蛋白和β/γ-连环蛋白的胞质表达缺失。E-钙黏蛋白的反应强度与组织学分级(p = 0.002)和肿瘤类型(p < 0.001)显著相关。小叶癌常表现出E-钙黏蛋白表达缺失,如其他研究报道;这些肿瘤中也发现了连环蛋白表达缺失。α-连环蛋白强度也与分级(p = 0.008)和雌激素受体(ER)状态(p = 0.006)有关。β/γ-连环蛋白表达与其他已知预后因素无关。分别有49%和42%的病例β1-整合素和α2-整合素无膜免疫染色,且发现β1-整合素和α2-整合素表达协同缺失。β1-整合素和α2-整合素表达均与组织学分级相关(分别为p = 0.003和p = 0.031),β1-整合素免疫反应性与肿瘤类型相关(p = 0.010)。尽管观察到一种趋势(p = 0.087),即β1-整合素表达缺失或较弱的肿瘤患者生存率较低,但所检测的变量均未显示与肿瘤大小、淋巴结分期或总生存存在统计学显著关联。这些标志物的表达具有生物学意义,但在预测临床行为方面似乎没有额外的作用。