Gene amplification in ductal carcinoma in situ of the breast

Gene amplification in ductal carcinoma in situ of the breast
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DOI:
10.1007/s10549-009-0675-8
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发表时间:
2010-10-01
影响因子:
3.8
通讯作者:
Lebeau, A.
Lebeau, A.
中科院分区:
医学2区
文献类型:
--
作者:
Burkhardt, L.;Grob, T. J.;Lebeau, A.

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多种不同的生物学和临床相关基因在浸润性乳腺癌中经常被扩增,包括HER2、ESR1、CCND1和MYC。到目前为止,人们对它们在肿瘤进展中的作用知之甚少。为了研究它们对肿瘤侵袭的意义,我们比较了单纯导管原位癌(DCIS)和浸润性癌相关的DCIS基因的扩增情况。对组织微阵列进行荧光原位杂交(FISH),其中包含130个纯DCIS和159个与浸润性乳腺癌相关的DCIS样本。对于后者,我们分别分析导管内和侵入性成分。此外,还包括23例浸润性癌的淋巴结转移。纯DCIS与浸润性癌相关的DCIS扩增率无显著差异(纯DCIS与浸润性癌相关的DCIS: HER2 22.7 vs. 24.2%, ESR1 19.0 vs. 24.1%, CCND1 10.0 vs. 14.8%, MYC 11.8 vs. 6.5%; P < 0.05)。此外,我们观察到所有基因的扩增状态高度一致,如果原位癌和侵袭性癌的个体患者进行比较。这也适用于相应的淋巴结转移。我们的研究结果显示DCIS和浸润性乳腺癌的HER2、ESR1、CCND1和MYC基因扩增状态无显著差异。因此,我们的数据表明,所有分析的基因扩增在乳腺癌发展中的早期作用,而不是在侵袭性肿瘤生长的开始。
Multiple different biologically and clinically relevant genes are often amplified in invasive breast cancer, including HER2, ESR1, CCND1, and MYC. So far, little is known about their role in tumor progression. To investigate their significance for tumor invasion, we compared pure ductal carcinoma in situ (DCIS) and DCIS associated with invasive cancer with regard to the amplification of these genes. Fluorescence in situ hybridization (FISH) was performed on a tissue microarray containing samples from 130 pure DCIS and 159 DCIS associated with invasive breast cancer. Of the latter patients, we analyzed the intraductal and invasive components separately. In addition, lymph node metastases of 23 patients with invasive carcinoma were included. Amplification rates of pure DCIS and DCIS associated with invasive cancer did not differ significantly (pure DCIS vs. DCIS associated with invasive cancer: HER2 22.7 vs. 24.2%, ESR1 19.0 vs. 24.1%, CCND1 10.0 vs. 14.8%, MYC 11.8 vs. 6.5%; P > 0.05). Furthermore, we observed a high concordance of the amplification status for all genes if in situ and invasive carcinoma of individual patients were compared. This applied also to the corresponding lymph node metastases. Our results indicate no significant differences between the gene amplification status of DCIS and invasive breast cancer concerning HER2, ESR1, CCND1, and MYC. Therefore, our data suggest an early role of all analyzed gene amplifications in breast cancer development but not in the initiation of invasive tumor growth.