Ghannam Suzan F, Rutland Catrin Sian, Allegrucci Cinzia, Mather Melissa L, Alsaleem Mansour, Bateman-Price Thomas D, Patke Rodhan, Ball Graham, Mongan Nigel P, Rakha Emad
Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
Faculty of Medicine, Department of Histology and Cell Biology, Suez Canal University, Ismailia, Egypt.
J Microsc. 2025 Feb;297(2):135-152. doi: 10.1111/jmi.13361. Epub 2024 Oct 3.
Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n = 100) and invasive tumours (n = 100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68 ± 11.2 fibre/µm) compared to DCIS (p < 0.0001). The collagen fibres were thinner (13.78 ± 1.08 µm), straighter (0.96 ± 0.006, on a scale of 0-1), more disorganised (95.07° ± 11.39°) and less aligned (0.20 ± 0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p < 0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.
乳腺癌（BC）具有高度异质性，这受到肿瘤细胞与肿瘤微环境相互作用的影响。肿瘤基质在乳腺癌中的诊断和预后作用仍有待明确。微分干涉差（DIC）显微镜检查是一种无标记成像技术，非常适合可视化细胞和组织等弱光学相位物体。本研究旨在使用DIC显微镜比较原位和浸润性乳腺肿瘤之间的基质胶原纤维特征，并研究胶原参数在乳腺癌中的预后价值。从200例病例中构建了组织微阵列，包括原位导管癌（DCIS；n = 100）和浸润性肿瘤（n = 100），并额外使用50例（25例浸润性乳腺癌和25例DCIS）病例进行验证。每个病例使用两张切片：一张用苏木精和伊红（H&E）染色用于组织学检查，另一张未染色用于DIC显微镜检查。测量了胶原纤维参数，包括取向角、纤维排列、纤维密度、纤维宽度、纤维长度和纤维直线度。与DCIS相比，浸润性乳腺癌基质中的胶原纤维密度更高（161.68±11.2纤维/μm）（p < 0.0001）。与DCIS相比，浸润性乳腺癌中的胶原纤维更细（13.78±1.08μm）、更直（0.96±0.006，范围为0 - 1）、更紊乱（95.07°±11.39°）且排列更不整齐（0.20±0.09，范围为0 - 1）（所有p < 0.0001）。开发了一个考虑这些特征的模型，该模型能够以94%的准确率区分DCIS和浸润性肿瘤。两组中纤维特征与临床病理参数之间均存在强相关性。在浸润性组中观察到纤维特征与患者预后（乳腺癌特异性生存和无复发生存）之间存在统计学显著关联，但在DCIS中未观察到。尽管浸润性乳腺癌和DCIS均与基质反应相关，但在两个疾病阶段胶原纤维的结构特征存在显著差异。术前粗针活检标本中基质纤维特征的分析可能有助于区分纯DCIS和与浸润相关的DCIS。
