Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma
Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma
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DOI：
10.1111/j.1464-410x.2006.06704.x
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发表时间：
2007-04-01
影响因子：
4.5
通讯作者：
Hamilton, Peter W.
中科院分区：
文献类型：
--
作者：
Mohamed, Mahmoud A.;Greif, Philipp A.;Hamilton, Peter W.
目的利用高分辨率计算机定量数字图像分析（DIA）技术，探讨核染色质表型、整体表观遗传机制、染色质重塑酶及其作为前列腺病变诊断生物标志物的作用。材料与方法利用78例患者的石蜡包埋前列腺组织构建组织微阵列（TMA），其中30例为良性前列腺增生（BPH）， 10例为低级别前列腺上皮内瘤变（LGPIN）， 38例为前列腺腺癌，20例为距LGPIN病变0.6-1 mm处切除的BPH组织，10例距高级别前列腺癌（HGPIN）病变0.6-1 mm处切除的BPH组织。利用高分辨率纹理分析评估血红素染色切片的染色质表型。在定量免疫组织化学中，使用针对乙酰化组蛋白H3赖氨酸9 （AcH3K9）、5'甲基胞苷（5MeC）和染色质重塑atp酶ISWI [SNF2H和SNF2L]的抗体。使用DIA测定免疫密度以确定病例的表观遗传谱。每个病例至少测量了60个核。结果两组在染色强度和核分布模式上的差异有统计学意义(p
OBJECTIVE To explore the nuclear chromatin phenotype, overall epigenetic mechanisms, chromatin remodelling enzymes and their role as diagnostic biomarkers in prostate lesions, using high-resolution computerized quantitative digital image analysis (DIA). MATERIALS ANDMETHODS A tissue microarray (TMA) was constructed using paraffin wax-embedded prostatic tissues from 78 patients, containing 30 cores of benign prostatic hyperplasia (BPH), 10 of low-grade prostatic intraepithelial neoplasia (LGPIN), 38 of prostate adenocarcinoma, 20 of BPH tissue excised at 0.6-1 mm from LGPIN lesions, and 10 of BPH prostatic tissues obtained 0.6-1 mm from high-grade PIN (HGPIN) lesions. Chromatin phenotype was assessed on haematoxylin-stained sections using high-resolution texture analysis. For quantitative immunohistochemistry, antibodies raised against acetylated histone H3 lysine 9 (AcH3K9), 5'methylcytidine (5MeC) and the chromatin remodelling ATPase ISWI [SNF2H and SNF2L] were used. The immunodensity was measured using DIA to determine the epigenetic profile of the cases. At least 60 nuclei were measured from each case.RESULTS There were many statistically Significant differences in staining intensity and nuclear distribution patterns in chromatin phenotype and immunostaining (p