Shin Eunah, Lee YuKyung, Koo Ja Seung
Department of Pathology, CHA Gangnam Medical Center, CHA University, Seoul, South Korea.
Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
J Transl Med. 2016 Apr 12;14:87. doi: 10.1186/s12967-016-0840-x.
We assessed the expression of methylation-related proteins 5-meC, DNMT1, and ISL-1 in breast cancer and evaluated their relationship to clinicopathological factors.
Immunohistochemical staining for ER, PR, HER-2, Ki-67, 5-meC, DNMT1, and ISL-1 were performed on 348 breast cancer samples in tissue microarray. Samples were subgrouped into luminal A, luminal B, HER-2, or triple-negative breast cancer (TNBC) according to immunohistochemical staining for ER, PR, HER-2, and Ki-67. The tumor stroma was histologically subtyped into desmoplastic, sclerotic, normal-like, or inflammatory type.
Tumor expression of DNMT1 differed by molecular subtype: it was higher in TNBC and lower in luminal A (p < 0.001) samples. DNMT1 expression was also related to higher histologic grade, ER negativity, PR negativity, and higher Ki-67 LI (p < 0.001). In western blot, protein expressions of DNMT1 and ISL-1 were higher in TNBC and relatively lower in the remaining subtypes. High tumor expression of DNMT1 was associated with shorter OS in univariate analysis (p = 0.041). DNMT1 and 5-meC were differentially expressed by stromal phenotype: 5-meC was higher in normal-like type and lower in sclerotic type (p = 0.049); DNMT1 was higher in inflammatory and lower in sclerotic type (p < 0.001).
Tumor expression of DNMT1 in breast cancer differed by molecular subtype and stromal histological type. DNMT1 was highly expressed in TNBC and in breast cancer with inflammatory stromal type.
我们评估了甲基化相关蛋白5-甲基胞嘧啶（5-meC）、DNA甲基转移酶1（DNMT1）和胰岛1（ISL-1）在乳腺癌中的表达，并评估了它们与临床病理因素的关系。
对组织芯片中的348例乳腺癌样本进行雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）、Ki-67、5-meC、DNMT1和ISL-1的免疫组织化学染色。根据ER、PR、HER-2和Ki-67的免疫组织化学染色结果，将样本分为腔面A型、腔面B型、HER-2型或三阴性乳腺癌（TNBC）。肿瘤间质在组织学上分为促纤维组织增生型、硬化型、正常样型或炎症型。
DNMT1的肿瘤表达因分子亚型而异：在TNBC中较高，在腔面A型中较低（p<0.001）。DNMT1表达也与更高的组织学分级、ER阴性、PR阴性和更高的Ki-67标记指数（p<0.001）相关。在蛋白质印迹法中，DNMT1和ISL-1的蛋白表达在TNBC中较高，在其余亚型中相对较低。在单因素分析中，DNMT1的高肿瘤表达与较短的总生存期相关（p=0.041）。DNMT1和5-meC因间质表型而差异表达：5-meC在正常样型中较高，在硬化型中较低（p=0.049）；DNMT1在炎症型中较高，在硬化型中较低（p<0.001）。
乳腺癌中DNMT1的肿瘤表达因分子亚型和间质组织学类型而异。DNMT1在TNBC和具有炎症性间质类型的乳腺癌中高表达。
