Aligned Collagen Is a Prognostic Signature for Survival in Human Breast Carcinoma
Aligned Collagen Is a Prognostic Signature for Survival in Human Breast Carcinoma
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DOI：
10.1016/j.ajpath.2010.11.076
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发表时间：
2011-03-01
影响因子：
6
通讯作者：
Keely, Patricia J.
中科院分区：
文献类型：
--
作者：
Conklin, Matthew W.;Eickhoff, Jens C.;Keely, Patricia J.
越来越多的证据表明间质组织和功能对乳腺肿瘤的侵袭和转移具有重要影响。我们对肿瘤相关胶原信号-3(Tacs-3)与人类患者长期存活率的关系进行了严格的研究。Tacs-3的特征是垂直于肿瘤边界的一束束拉直和排列的胶原纤维。通过对胶原蛋白产生的背向散射信号进行二次谐波成像，在196例患者的活检组织切片中对Tacs-3进行了评估。COX比例风险模型的单变量分析表明，Tacs-3的存在与较差的疾病特异性和无疾病生存率相关，导致风险比在3.0至3.9之间。此外，Tacs-3被证实是一个独立的预后指标，与肿瘤的分级和大小、雌激素或孕激素受体状态、人表皮生长因子受体-2状态、结节状态和肿瘤亚型无关。有趣的是，Tacs-3与基质Syndecan-1的表达呈正相关，后者是包括胶原蛋白在内的几种细胞外基质蛋白的受体。由于有强有力的统计学证据表明Tacs患者的存活率较低，而且该评估可以在通过二次谐波产生或使用微天狼星成像的常规组织病理学样本中进行，因此我们建议量化胶原排列是预测人类乳腺癌存活期的一种可行的新范例。(Am J Pathol 2011,178：1221-1232；DOI：10.1016/j/ajpath.2010.11.076 DOI.10.1016/j.ajpath.2010.11.076 DOI：10.1016/j.ajpath.2010.11.076)
Evidence for the potent influence of stromal organization and function on invasion and metastasis of breast tumors is ever growing. We have performed a rigorous examination of the relationship of a tumor-associated collagen signature-3 (TACS-3) to the long-term survival rate of human patients. TACS-3 is characterized by bundles of straightened and aligned collagen fibers that are oriented perpendicular to the tumor boundary. An evaluation of TACS-3 was performed in biopsied tissue sections from 196 patients by second harmonic generation imaging of the back-scattered signal generated by collagen. Univariate analysis of a Cox proportional hazard model demonstrated that the presence of TACS-3 was associated with poor disease-specific and disease-free survival, resulting in hazard ratios between 3.0 and 3.9. Furthermore, TACS-3 was confirmed to be an independent prognostic indicator regardless of tumor grade and size, estrogen or progesterone receptor status, human epidermal growth factor receptor-2 status, node status, and tumor subtype. Interestingly, TACS-3 was positively correlated to expression of stromal syndecan-1, a receptor for several extracellular matrix proteins including collagens. Because of the strong statistical evidence for poor survival in patients with TACS, and because the assessment can be performed in routine histopathological samples imaged via second harmonic generation or using picrosirius, we propose that quantifying collagen alignment is a viable, novel paradigm for the prediction of human breast cancer survival. (Am J Pathol 2011, 178:1221-1232; DOI: 10.1016/j/ajpath.2010.11.076 DOI. 10.1016/j.ajpath.2010.11.076 DOI: 10.1016/j.ajpath.2010.11.076)