Expression of Histone Deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in Invasive Ductal Carcinomas of the Breast.
Expression of Histone Deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in Invasive Ductal Carcinomas of the Breast.
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DOI：
10.4048/jbc.2014.17.4.323
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发表时间：
2014-12
影响因子：
2.4
通讯作者：
Ju YS
中科院分区：
文献类型：
--
作者：
Seo J;Min SK;Park HR;Kim DH;Kwon MJ;Kim LS;Ju YS
组蛋白去乙酰化酶（HDAC）引起的DNA去乙酰化是乳腺癌发生的重要机制。先前的研究已经报道了雌激素受体（ER）与HDAC的关联，并且通过体外实验证明了HDAC抑制剂用于治疗乳腺癌的功效。在这项研究中，我们研究了HDAC表达与临床病理参数和疾病特异性生存的关系。使用组织微阵列对300例浸润性导管癌进行HDAC1、HDAC2、HDAC3和HDAC6的免疫组织化学（IHC）分析。通过染色强度（0至3）和染色比例（0至4）的乘积确定IHC评分，我们将肿瘤分为低HDAC表达组和高HDAC表达组。HDAC1的高表达与分子亚型（p=0.001）和人表皮生长因子2（HER2）扩增（p=0.012）相关。HDAC6的高表达与年轻（p<0.001）、ER表达（p=0.025）、孕酮受体表达（p=0.034）、分子亚型（p=0.023）和HER2扩增（p=0.011）相关。HDAC 1高表达与管腔A型肿瘤相关（p=0.001），而HDAC 6高表达在管腔B型肿瘤中更常见（p=0.023）。虽然HDAC的表达在整个队列中没有表现出预后意义，但在单变量分析中，HDAC 1和HDAC 6的高表达与ER阳性肿瘤患者的总生存期（OS）改善相关（分别为p=0.017和p=0.029），HDAC 2的高表达与ER阴性肿瘤患者的OS改善相关（p=0.048）。此外，在多变量分析中，HDAC6高表达与改善的无病生存期相关（p=0.048）。HDAC1表达与肿瘤的分子亚型显著相关，在管腔A型肿瘤中观察到最高表达。HDAC6与ER表达和分子亚型显著相关，从而支持HDAC6的雌激素调节特性。HDAC1和HDAC6表达是ER阳性肿瘤的良好预后因素。
DNA deacetylation by histone deacetylase (HDAC) is an important mechanism involved in the oncogenic tumorigenesis of breast cancer. Previous studies have reported an association of the estrogen receptor (ER) with HDACs and demonstrated the efficacy of HDAC inhibitors for the treatment of breast cancers via in vitro experiments. In this study, we examined the association of HDAC expression with clinicopathological parameters and disease-specific survival. Immunohistochemical (IHC) analysis of HDAC1, HDAC2, HDAC3, and HDAC6 was performed using tissue microarrays in 300 invasive ductal carcinomas. IHC scoring was determined by multiplication of the intensity (0 to 3) and the proportion (0 to 4) of staining, and we classified tumors into low- and high-HDAC expression groups. High expression of HDAC1 was correlated with the molecular subtype (p=0.001) and human epidermal growth factor 2 (HER2) amplification (p=0.012). High expression of HDAC6 was correlated with a younger age (p<0.001), ER expression (p=0.025), progesterone receptor expression (p=0.034), molecular subtype (p=0.023), and HER2 amplification (p=0.011). High HDAC1 expression was correlated with luminal A tumors (p=0.001), while high HDAC6 expression was more common in luminal B tumors (p=0.023). Although the expression of HDACs did not exhibit prognostic significance in the entire cohort, high expression of HDAC1 and HDAC6 was associated with improved overall survival (OS) in patients with ER-positive tumors (p=0.017 and p=0.029, respectively), and high expression of HDAC2 was correlated with improved OS in ER-negative tumors (p=0.048) on univariate analysis. Furthermore, high HDAC6 expression was associated with improved disease-free survival (p=0.048) on multivariate analysis. HDAC1 expression is significantly correlated with the molecular subtypes of tumors, with the highest expression being observed in luminal A tumors. HDAC6 is a significantly correlated with ER expression and the molecular subtype, thereby supporting the estrogen regulatory property of HDAC6. HDAC1 and HDAC6 expression are good prognostic factors for ER-positive tumors.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
64.5
作者：
Kawaguchi, Y;Kovacs, JJ;Yao, TP
通讯作者：
Yao, TP
影响因子：
3.8
作者：
Müller BM;Jana L;Kasajima A;Lehmann A;Prinzler J;Budczies J;Winzer KJ;Dietel M;Weichert W;Denkert C
通讯作者：
Denkert C
DOI：
10.1158/1078-0432.ccr-08-2319
发表时间：
2009-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Suzuki J;Chen YY;Scott GK;Devries S;Chin K;Benz CC;Waldman FM;Hwang ES
通讯作者：
Hwang ES
影响因子：
11.5
作者：
Bali, P;Pranpat, M;Bhalla, K
通讯作者：
Bhalla, K