Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides.

Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides.
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DOI:
10.1038/sj.bjc.6603147
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发表时间:
2006-06-05
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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在一些研究中,细胞周期蛋白A与乳腺癌的低存活率有关,尽管所有的研究都没有证实这一点。它在乳腺癌中的预后意义需要在更大规模的研究中进行评估。组织微阵列(TMA)技术可以在一张显微镜载玻片上同时分析大量肿瘤。这使得在大量肿瘤中快速筛选分子标记成为可能。因为每个肿瘤只有一小部分组织样本被打孔在阵列上,所以当研究只在一小部分细胞中表达的标记时,TMA的代表性就产生了问题。为此,我们想要比较周期蛋白A在TMA和传统大切片上的表达。两个乳腺癌TMA是在1997-1998年间诊断的200个乳腺肿瘤中构建的。对这200个肿瘤的TMA切片和传统大切片切片进行Cyclin A抗体染色,并由两个独立的阅读器进行分析。两种读数的重复性很好,甚至非常好,卡伯值在0.71-0.87之间。TMA与大断面结果吻合较好,卡伯值在0.62~0.75之间。细胞周期蛋白A的过度表达与雌激素受体和孕激素受体阴性显著相关(P<0.001),且在子宫肌瘤和大块切片上均为高级别。在TMA和大切片上,Cyclin A的过度表达与较差的无转移生存率显著相关。TMA和大切面转移的相对风险相似。本研究提示TMA技术可用于大规模研究细胞周期蛋白A在乳腺癌中的组织学相关性和预后意义。
Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997–1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers’ results was good or even very good, with kappa values 0.71–0.87. The agreement of TMA and large section results was good with kappa value 0.62–0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.
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Michalides, R;van Tinteren, H;Balkenende, A;Vermorken, J B;Benraadt, J;Huldij, J;van Diest, P
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发表时间: 1999-11-01
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DOI: 10.1038/nm0798-844
发表时间: 1998-07-01
期刊: NATURE MEDICINE
影响因子: 82.9
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