在早期乳腺癌女性中，细胞角蛋白 5 和紧密连接蛋白 3 的表达与 BRCA1 和 BRCA2 种系突变的相关性。

Association of Cytokeratin 5 and Claudin 3 expression with BRCA1 and BRCA2 germline mutations in women with early breast cancer.

机构信息

Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.

Department of Pathology, Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.

出版信息

BMC Cancer. 2019 Jul 15;19(1):695. doi: 10.1186/s12885-019-5908-6.

DOI:10.1186/s12885-019-5908-6

PMID:31307407

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6631579/

Abstract

BACKGROUND

It is important to identify biomarkers associated with BRCA mutation in women with early breast cancer (BC) to improve early identification of mutation carriers. Thus, in this study, we examined the protein expression of claudin (CLDN) 3, CLDN4, CLDN7, and E-cadherin. Moreover, we analyzed additional histopathological variables and their associations in familial BC.

METHODS

Immunohistochemical analysis for CLDNs and E-cadherin was performed on 237 BC cases of three different subsets of BC tumors: 62 from BRCA1 mutation carriers, 59 from BRCA2 mutation carriers, and 116 tumors from patients with BRCA wild type (WT) as controls. Histopathological data were also analyzed in the different subgroups. Logistic regression and receiver operation characteristic (ROC) curve were conducted to investigate factors associated with BRCA tumors.

RESULTS

Expression of CLDN3 positively correlated with BRCA-mutated BC. CLDN3 was expressed in 58% of BRCA1-mutated tumors compared to only 7% in BRCA2-mutated tumors (p < 0.001) and 1% in WT tumors (p < 0.001). CK5 and CK14 expression were also more likely to arise in BRCA1 tumors (44 and 16%, respectively) than in the control group (8 and 4%) (p < 0.001, p = 0.012, respectively). We also found a significantly higher proportion of CK5+ among BRCA1 tumors (44%) in comparison with BRCA2-related BC (8%) (p < 0.001). In addition, there was a significant difference between both groups regarding CK14: positive expression in 16 and 5%, respectively (p = 0.030). CK5 and CK14 did not differ between the BRCA2 group and the WT tumors significantly. In a multivariate regression model, expression of CK5 (Odds ratio (OR): 6.46; 95% confidence interval (CI): 1.52-27.43; p = 0.011), and CLDN3 (OR: 200.48; 95% CI: 21.52-1867.61; p < 0.001) were associated with BRCA1 mutation status.

CONCLUSIONS

Our data suggests that CLDN3, CK5, and CK14 in combination with ER, PR and HER2 are associated with BRCA1 mutation status.

摘要

背景

在患有早期乳腺癌（BC）的女性中，识别与 BRCA 突变相关的生物标志物对于提高突变携带者的早期识别非常重要。因此，在这项研究中，我们检测了紧密连接蛋白（CLDN）3、CLDN4、CLDN7 和 E-钙黏蛋白的蛋白表达。此外，我们分析了家族性 BC 中的其他组织病理学变量及其相关性。

方法

对 237 例 BC 病例进行了 CLDNs 和 E-钙黏蛋白的免疫组织化学分析，这些病例分为三组不同的 BC 肿瘤：62 例来自 BRCA1 突变携带者，59 例来自 BRCA2 突变携带者，116 例来自 BRCA 野生型（WT）的患者作为对照。还分析了不同亚组的组织病理学数据。进行逻辑回归和接收者操作特征（ROC）曲线分析以研究与 BRCA 肿瘤相关的因素。

结果

CLDN3 的表达与 BRCA 突变型 BC 呈正相关。BRCA1 突变型肿瘤中 CLDN3 的表达率为 58%，而 BRCA2 突变型肿瘤中仅为 7%（p<0.001），WT 肿瘤中为 1%（p<0.001）。CK5 和 CK14 的表达也更可能出现在 BRCA1 肿瘤中（分别为 44%和 16%），而不是对照组（8%和 4%）（p<0.001，p=0.012）。我们还发现 BRCA1 肿瘤中 CK5+的比例显著高于 BRCA2 相关 BC（44%比 8%）（p<0.001）。此外，两组之间 CK14 的表达存在显著差异：阳性表达分别为 16%和 5%（p=0.030）。CK5 和 CK14 在 BRCA2 组和 WT 肿瘤之间没有显著差异。在多变量回归模型中，CK5 的表达（优势比（OR）：6.46；95%置信区间（CI）：1.52-27.43；p=0.011）和 CLDN3 的表达（OR：200.48；95%CI：21.52-1867.61；p<0.001）与 BRCA1 突变状态相关。