Blanchard Anne A, Skliris George P, Watson Peter H, Murphy Leigh C, Penner Carla, Tomes Ladislav, Young Tamara L, Leygue Etienne, Myal Yvonne
Department of Pathology, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E0W3.
Virchows Arch. 2009 Jun;454(6):647-56. doi: 10.1007/s00428-009-0770-6. Epub 2009 Apr 23.
In the present study we investigated the protein expression of claudins 1, 3, and 4 and their relationship to clinical variables and outcome in a cohort of ER-ve and ER+ve human invasive breast cancers. Immunohistochemical analysis was performed on tissue microarrays representing a total of 412 tumors and interpretable data was derived from 314, 299, and 306 tumors for claudins 1, 3, and 4, respectively. In the ER+ve subset, 5%, 89%, and 52%, and in the ER-ve subset, 39%, 79%, and 79% of tumors stained positively for claudins 1, 3, and 4, respectively (p < 0.0001, p = 0.026, p < 0.0001). Thus, in the two subsets, a significantly higher number of tumors were positive for claudins 3 and 4, compared to claudin 1. In addition, protein expressions of claudins 1 and 4 were significantly higher in those tumors that displayed characteristics of the basal-like subtype of breast cancers (ER-ve, Her-2-ve, EGFR+ve, CK5/6+ve). This study shows a unique pattern of expression for the different claudins in ER-ve and ER+ve tumors. Our data also suggests that increased expression of claudins 1 and 4 was associated with the basal-like subtype of breast cancers, a subtype generally linked to poor outcome.
在本研究中，我们调查了闭合蛋白1、3和4的蛋白表达及其与雌激素受体阴性（ER-ve）和雌激素受体阳性（ER+ve）的人类浸润性乳腺癌队列中临床变量及预后的关系。对代表总共412个肿瘤的组织微阵列进行了免疫组织化学分析，分别从314、299和306个肿瘤中获得了关于闭合蛋白1、3和4的可解释数据。在ER+ve亚组中，分别有5%、89%和52%的肿瘤对闭合蛋白1、3和4呈阳性染色；在ER-ve亚组中，分别有39%、79%和79%的肿瘤对闭合蛋白1、3和4呈阳性染色（p<0.0001，p = 0.026，p<0.0001）。因此，在这两个亚组中，与闭合蛋白1相比，闭合蛋白3和4呈阳性的肿瘤数量显著更多。此外，在那些表现出基底样亚型乳腺癌特征（ER-ve、Her-2-ve、EGFR+ve、CK5/6+ve）的肿瘤中，闭合蛋白1和4的蛋白表达显著更高。本研究显示了ER-ve和ER+ve肿瘤中不同闭合蛋白的独特表达模式。我们的数据还表明，闭合蛋白1和4表达的增加与基底样亚型乳腺癌相关，该亚型通常与不良预后有关。
