Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Breast Cancer Res Treat. 2012 Aug;135(1):115-24. doi: 10.1007/s10549-012-2125-2. Epub 2012 Jun 16.
Accurate detection of breast malignancy from histologically normal cells ("field effect") has significant clinical implications in a broad base of breast cancer management, such as high-risk lesion management, personalized risk assessment, breast tumor recurrence, and tumor margin management. More accurate and clinically applicable tools to detect markers characteristic of breast cancer "field effect" that are able to guide the clinical management are urgently needed. We have recently developed a novel optical microscope, spatial-domain low-coherence quantitative phase microscopy, which extracts the nanoscale structural characteristics of cell nuclei (i.e., nuclear nano-morphology markers), using standard histology slides. In this proof-of-concept study, we present the use of these highly sensitive nuclear nano-morphology markers to identify breast malignancy from histologically normal cells. We investigated the nano-morphology markers from 154 patients with a broad spectrum of breast pathology entities, including normal breast tissue, non-proliferative benign lesions, proliferative lesions (without and with atypia), "malignant-adjacent" normal tissue, and invasive carcinoma. Our results show that the nuclear nano-morphology markers of "malignant-adjacent" normal tissue can detect the presence of invasive breast carcinoma with high accuracy and do not reflect normal aging. Further, we found that a progressive change in nuclear nano-morphology markers that parallel breast cancer risk, suggesting its potential use for risk stratification. These novel nano-morphology markers that detect breast cancerous changes from nanoscale structural characteristics of histologically normal cells could potentially benefit the diagnosis, risk assessment, prognosis, prevention, and treatment of breast cancer.
从组织学上正常的细胞（“场效应”）中准确检测乳腺癌具有广泛的乳腺癌管理基础的重要临床意义，例如高危病变管理、个性化风险评估、乳腺肿瘤复发和肿瘤边缘管理。迫切需要更准确和更适用于临床的工具来检测具有乳腺癌“场效应”特征的标志物，这些标志物能够指导临床管理。我们最近开发了一种新型光学显微镜，即空间域低相干定量相显微镜，该显微镜使用标准组织学载玻片提取细胞核的纳米级结构特征（即核纳米形态标志物）。在这项概念验证研究中，我们提出使用这些高度敏感的核纳米形态标志物来从组织学上正常的细胞中识别乳腺癌。我们研究了来自 154 名患者的纳米形态标志物，这些患者具有广泛的乳腺病理学实体，包括正常乳腺组织、非增殖性良性病变、增殖性病变（无和有非典型性）、“恶性相邻”正常组织和浸润性癌。我们的结果表明，“恶性相邻”正常组织的核纳米形态标志物可以高精度地检测出浸润性乳腺癌的存在，并且不会反映正常老化。此外，我们发现核纳米形态标志物的逐渐变化与乳腺癌风险平行，这表明其可能用于风险分层。这些从组织学上正常细胞的纳米级结构特征中检测乳腺癌变化的新型纳米形态标志物可能有益于乳腺癌的诊断、风险评估、预后、预防和治疗。
