Different gene expression patterns in invasive lobular and ductal carcinomas of the breast
Different gene expression patterns in invasive lobular and ductal carcinomas of the breast
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DOI：
10.1091/mbc.e03-11-0786
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发表时间：
2004-06-01
影响因子：
3.3
通讯作者：
Jeffrey, SS
中科院分区：
文献类型：
--
作者：
Zhao, HJ;Langerod, A;Jeffrey, SS
浸润性导管癌（IDC）和浸润性小叶癌（ILC）是世界范围内乳腺癌的两种主要组织学类型。尽管IDC的发病率一直保持稳定，但在美国和西欧，ILC是增长最快的乳腺癌表型。目前尚不清楚IDC和ILC是否代表分子上不同的实体，以及哪些基因可能参与了这两种表型的发展。我们进行了全面的基因表达谱研究来解决这些问题。从21个ILCs， 38个IDCs， 2个淋巴结转移和3个正常组织中扩增总RNA并杂交成类似于42,000个克隆cDNA微阵列。使用分层聚类算法和统计分析分析数据，识别差异表达基因（微阵列的显著性分析）和最小基因子集（微阵列的预测分析），简洁地区分ILCs和idc。21个ILCs中有11个（52%）聚集在一起，显示出与IDC不同的基因表达谱，而其他ILCs（“导管样”ILCs）分布在不同的IDC亚型之间。ilc和idc之间的许多差异表达基因编码涉及细胞粘附/运动、脂质/脂肪酸运输和代谢、免疫/防御反应和电子传递的蛋白质。许多区分典型和导管样ILCs的基因参与细胞生长和免疫反应的调节。我们的数据强烈表明，超过一半的ILCs与IDCs不仅在组织学和临床特征上不同，而且在全球转录程序上也不同。其余的ilc在转录模式上与idc非常相似。需要进一步的研究来探索ILC分子亚型之间的差异，并确定它们是否需要不同的治疗策略。
Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological types of breast cancer worldwide. Whereas IDC incidence has remained stable, ILC is the most rapidly increasing breast cancer phenotype in the United States and Western Europe. It is not clear whether IDC and ILC represent molecularly distinct entities and what genes might be involved in the development of these two phenotypes. We conducted comprehensive gene expression profiling studies to address these questions. Total RNA from 21 ILCs, 38 IDCs, two lymph node metastases, and three normal tissues were amplified and hybridized to similar to42,000 clone cDNA microarrays. Data were analyzed using hierarchical clustering algorithms and statistical analyses that identify clifferentially expressed genes (significance analysis of microarrays) and minimal subsets of genes (prediction analysis for microarrays) that succinctly distinguish ILCs and IDCs. Eleven of 21 (52%) of the ILCs ("typical" ILCs) clustered together and displayed different gene expression profiles from IDCs, whereas the other ILCs ("ductal-like" ILCs) were distributed between different IDC subtypes. Many of the differentially expressed genes between ILCs and IDCs code for proteins involved in cell adhesion/motility, lipid/fatty acid transport and metabolism, immune/defense response, and electron transport. Many genes that distinguish typical and ductal-like ILCs are involved in regulation of cell growth and immune response. Our data strongly suggest that over half the ILCs differ from IDCs not only in histological and clinical features but also in global transcription programs. The remaining ILCs closely resemble IDCs in their transcription patterns. Further studies are needed to explore the differences between ILC molecular subtypes and to determine whether they require different therapeutic strategies.