Talvinen K, Tuikkala J, Nykänen M, Nieminen A, Anttinen J, Nevalainen O S, Hurme S, Kuopio T, Kronqvist P
Department of Pathology, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
J Cancer Res Clin Oncol. 2010 Sep;136(9):1377-87. doi: 10.1007/s00432-010-0789-8. Epub 2010 Feb 12.
The study focuses on p120catenin, a regulator of cell adhesion, which has previously been described in many malignancies and suggested with a role in invasion and metastatic behaviour. In this study, we investigate the role of altered immunoexpression of p120catenin isoforms in the prognosis of invasive breast cancer (n = 351).
We used cDNA microarrays to screen differences in gene expression in invasive breast cancer in general, and between local and metastasized disease particularly. On this basis, we performed p120catenin immunohistochemistry in order to confirm the prognostic value of p120catenin isoforms on tissue microarrays comprising 341 patients from the era of mammographic screening, directed to modern surgical and oncological treatments, and followed-up for maximum of 20 years.
In cDNA microarray analysis, p120catenin was discovered down-regulated along with E-cadherin and alpha-catenin. In addition, p120catenin distinguished metastasized breast cancer from local disease. Immunohistochemistry confirmed the value of p120catenin as an independent prognosticator of breast cancer survival. In our results, p120catenin was associated with 3.7-fold risk of breast cancer death in multivariate Cox's regression analyses adjusted for the established prognosticators of breast cancer (p = 0.039). Particularly, the long isoform of p120catenin predicted metastatic disease (p = 0.029).
The present paper is the first report on p120catenin in invasive breast cancer based on a well-characterized patient material with long-term follow-up. We observed altered expression of p120catenin isoforms in invasive breast cancer and, in our material, the decrease in p120 immunoexpression was significantly associated with poor outcome of disease.
本研究聚焦于细胞黏附调节因子p120连环蛋白,此前已在多种恶性肿瘤中有所描述,并提示其在侵袭和转移行为中发挥作用。在本研究中,我们调查了p120连环蛋白异构体免疫表达改变在浸润性乳腺癌(n = 351)预后中的作用。
我们使用cDNA微阵列筛选浸润性乳腺癌总体上以及局部和转移疾病之间的基因表达差异。在此基础上,我们进行了p120连环蛋白免疫组织化学,以确认p120连环蛋白异构体在组织微阵列上对341例接受乳房X线筛查时代患者的预后价值,这些患者接受了现代外科和肿瘤治疗,并进行了最长20年的随访。
在cDNA微阵列分析中,发现p120连环蛋白与E-钙黏蛋白和α-连环蛋白一起下调。此外,p120连环蛋白可区分转移性乳腺癌和局部疾病。免疫组织化学证实p120连环蛋白作为乳腺癌生存的独立预后指标的价值。在我们的结果中,在针对已确定的乳腺癌预后指标进行调整的多变量Cox回归分析中,p120连环蛋白与乳腺癌死亡风险增加3.7倍相关(p = 0.039)。特别是,p120连环蛋白的长异构体可预测转移性疾病(p = 0.029)。
本文是基于具有长期随访的特征明确的患者材料对浸润性乳腺癌中p120连环蛋白的首次报道。我们观察到浸润性乳腺癌中p120连环蛋白异构体的表达改变,并且在我们的材料中,p120免疫表达的降低与疾病的不良预后显著相关。