Gonzalez L O, Corte M D, Vazquez J, Junquera S, Sanchez R, Viña A, Rodriguez J C, Lamelas M L, Vizoso F
Unidad de Investigación, Hospital de Jove, Gijón, Spain.
Histopathology. 2008 Oct;53(4):403-15. doi: 10.1111/j.1365-2559.2008.03136.x.
To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS).
An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP-7 and TIMP-1 than pure DCIS, as well as a higher expression rate of MMP-9 and TIMP-3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP-9 and -11 and TIMP-3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP-2, -14 and TIMP-1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS.
The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.
分析金属蛋白酶（MMPs）及其抑制剂（TIMPs）在乳腺导管原位癌（DCIS）中的表达情况。
采用组织芯片以及针对MMPs和TIMPs的特异性抗体，对56例单纯DCIS患者、39例伴有浸润性癌（IDC）的DCIS患者以及63例T1期IDC患者进行免疫组化研究。使用特定软件程序对免疫组化结果进行分类。通过对每种细胞类型进行无监督层次聚类分析来分析数据。IDC显示出比单纯DCIS更高的MMP-7和TIMP-1表达率，以及比混合病例中的DCIS成分更高的MMP-9和TIMP-3表达率，而单纯DCIS显示出比混合病例中的DCIS成分更高的MMP-9和-11以及TIMP-3表达率。伴有导管周围炎性浸润的单纯DCIS显示出显著更高的MMP-2、-14和TIMP-1。树形图在单纯DCIS肿瘤导管周围的肿瘤细胞和成纤维细胞或单核炎性细胞中识别出两个具有不同MMP/TIMP表达谱的聚类组。
结果表明DCIS在MMP/TIMP表达方面存在明显差异，这可能在乳腺癌中具有潜在的生物学和临床意义。
