Claudin expression in high-grade invasive ductal carcinoma of the breast: correlation with the molecular subtype.
Claudin expression in high-grade invasive ductal carcinoma of the breast: correlation with the molecular subtype.
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DOI：
10.1038/modpathol.2012.187
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发表时间：
2013-04
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紧密连接蛋白是紧密连接的主要组成部分。在许多恶性肿瘤中已经描述了紧密连接蛋白表达的失调。基因表达谱将乳腺癌分为不同的分子亚型：管腔型、HER 2+型和基底样型。最近，一种新的claudin-低分子亚型已被描述。在这项研究中，我们将密蛋白的表达模式与乳腺癌的分子亚型相关联。根据免疫组化表达，226例3级浸润性导管癌分为65例管腔型（ER+）、65例HER 2阳性（HER 2+）、86例基底样癌（包括14例化生癌（ER-、HER 2-、CK 5/6和/或EGFR+））和10例未分类。通过免疫组织化学分析组织微阵列中claudins 1、3、4、7和8的表达，并进行半定量评分。在17%的所有病例中检测到紧密连接蛋白1、32%紧密连接蛋白3、41%紧密连接蛋白4、44%紧密连接蛋白7和40%紧密连接蛋白8的高水平表达。管腔癌表现出增加的密蛋白7和8;基底样肿瘤表现出增加的密蛋白1和4表达。在226例病例中的30例（13%）中检测到所有五种claudin的低表达，该组被指定为“claudin低”。大多数claudin低亚组是基底细胞样癌（23/30，77%）。相比之下，30例claudin低表达的肿瘤中只有1例（3%）为管腔型，30例中有6例（20%）为HER 2+（P<0.001）。在基底样亚组中，64%的化生性肿瘤和19%的非化生性肿瘤为低密蛋白。低密蛋白组与疾病复发密切相关（P=0.0093）。总之，这项研究是第一个全面检查claudins 1，3，4，7和8在高级别乳腺癌的分子亚型的差异表达。Claudin低亚型是化生性和基底样乳腺癌中的常见现象，似乎是疾病复发的强预测因子。
Claudin proteins are a major component of the tight junctions. Dysregulation of claudin protein expression has been described in a number of malignancies. Gene expression profiling has stratified breast cancers into distinct molecular subtypes: luminal, HER2+ and basal-like. Recently, a novel claudin-low molecular subtype has been described. In this study we correlated the expression patterns of claudins with the molecular subtypes of breast cancer. On the basis of immunohistochemical expression 226 grade 3 invasive ductal carcinomas were stratified into 65 luminal (ER+), 65 HER2 positive (HER2+), 86 basal-like, including 14 metaplastic carcinomas (ER−, HER2−, CK5/6 and /or EGFR+), and 10 unclassified. Tissue microarrays were analyzed for expression of claudins 1, 3, 4, 7 and 8 by immunohistochemistry and scored semiquantitatively. High levels of expression were detected in 17% of all cases for claudin 1, 32% claudin 3, 41% claudin 4, 44% claudin 7, and 40% claudin 8. Luminal cancers exhibited increased claudins 7 and 8; basal-like tumors demonstrated increased claudins 1 and 4 expression. Low expression of all five claudins was detected in 30 of 226 cases (13%) and this group was designated “claudin-low”. The majority of the claudin-low subgroup were basal-like cancers (23 of 30, 77%). In contrast, only 1 of 30 (3%) claudin-low tumors were of the luminal phenotype and 6 of 30 cases (20%) were HER2+ (P<0.001). Within the basal-like subgroup, 64% of the metaplastic and 19% of the non-metaplastic tumors were claudin-low. The claudin-low group was strongly associated with disease recurrence (P=0.0093). In conclusion, this study is the first to comprehensively examine the differential expression of claudins 1, 3, 4, 7 and 8 in the molecular subtypes of high grade breast cancer. Claudin-low subtype is a frequent phenomenon in metaplastic and basal-like breast cancer and appears to be a strong predictor of disease recurrence.
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影响因子：
6.4
作者：
Lanigan, Fiona;McKiernan, Eadaoin;Gallagher, William M.
通讯作者：
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影响因子：
12.3
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Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
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2.8
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3.3
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Moss, SF
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