Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.

Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.
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DOI:
10.1186/1471-2407-7-55
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发表时间:
2007-03-27
期刊:
影响因子:
3.8
通讯作者:
Kolar, Zdenek
Kolar, Zdenek
中科院分区:
医学2区
文献类型:
--
作者:
Turashvili, Gulisa;Bouchal, Jan;Baumforth, Karl;Wei, Wenbin;Dziechciarkova, Marta;Ehrmann, Jiri;Klein, Jiri;Fridman, Eduard;Skarda, Jozef;Srovnal, Josef;Hajduch, Marian;Murray, Paul;Kolar, Zdenek

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浸润性导管癌和小叶癌(IDC和ILC)是最常见的乳腺癌组织学类型。临床随访数据和转移模式表明,这些肿瘤的发展和进展是不同的。本研究的目的是确定IDC和ILC与正常乳腺上皮细胞的基因表达谱。我们检查了30个样本(正常导管和小叶细胞从10例患者,IDC细胞从5例患者,ILC细胞从5例患者)从冷冻切片的10个乳腺切除术标本绝经后患者的显微解剖。通过PCR和体外转录扩增并标记50纳克的总RNA。在Affytron U133 Plus 2.0阵列上分析样品。通过免疫组织化学方法在组织芯片上验证7个差异表达基因(CDH 1、EMP 1、DDR 1、DVL 1、KRT 5、KRT 6、KRT 17)的表达。用原位杂交法检测ASPN mRNA的表达,用PCR法检测CTHRC 1、ASPN和COL 3A 1的表达。使用GCOS成对比较算法和秩积,我们已经确定了84个命名基因共同ILC与正常细胞类型,74个命名基因共同IDC与正常细胞类型,78个命名基因之间的差异表达正常导管和小叶细胞,和28个命名基因IDC和ILC之间。区分IDC和ILC的基因参与上皮-间充质转化、TGF-β和Wnt信号传导。这些变化存在于两种肿瘤类型中,但在ILC中似乎更突出。免疫组化检测几种新的标志物(EMP 1、DVL 1、DDR 1)可区分大组IDC和ILC。IDC和ILC可以在基因和蛋白水平上区分。在这项研究中,我们报告了两个候选基因,asporin(ASPN)和胶原蛋白三螺旋重复1(CTHRC 1),这可能是重要的乳腺癌发生。除了E-cadherin,在组织芯片上验证的蛋白质(EMP 1,DVL 1,DDR 1)可能是有助于区分IDC和ILC的新的免疫组织化学标记物。需要进一步研究更大的患者集,以验证各种组织学类型的乳腺癌的基因表达谱,以确定分子亚分类,预后和最佳治疗策略。
Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.
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发表时间: 2003-07-21
影响因子: 7.8
作者:
Ai, Xingbin;Do, Anh-Tri;Lozynska, Olga;Kusche-Gullberg, Marion;Lindahl, Ulf;Emerson, Charles P Jr
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影响因子: 6.4
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发表时间: 1999-10-01
影响因子: 6
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