Millar Ewan Ka, Browne Lois H, Beretov Julia, Lee Kirsty, Lynch Jodi, Swarbrick Alexander, Graham Peter H
Department of Anatomical Pathology, NSW Health Pathology, St George Hospital, Kogarah, NSW 2217, Australia.
St George & Sutherland Clinical School, UNSW Sydney, Kensington, NSW 2052, Australia.
Cancers (Basel). 2020 Dec 13;12(12):3749. doi: 10.3390/cancers12123749.
We aimed to determine the clinical significance of tumour stroma ratio (TSR) in luminal and triple negative breast cancer (TNBC) using digital image analysis and machine learning algorithms. Automated image analysis using QuPath software was applied to a cohort of 647 breast cancer patients (403 luminal and 244 TNBC) using digital H&E images of tissue microarrays (TMAs). Kaplan-Meier and Cox proportional hazards were used to ascertain relationships with overall survival (OS) and breast cancer specific survival (BCSS). For TNBC, low TSR (high stroma) was associated with poor prognosis for both OS (HR 1.9, CI 1.1-3.3, = 0.021) and BCSS (HR 2.6, HR 1.3-5.4, = 0.007) in multivariate models, independent of age, size, grade, sTILs, lymph nodal status and chemotherapy. However, for luminal tumours, low TSR (high stroma) was associated with a favourable prognosis in MVA for OS (HR 0.6, CI 0.4-0.8, = 0.001) but not for BCSS. TSR is a prognostic factor of most significance in TNBC, but also in luminal breast cancer, and can be reliably assessed using quantitative image analysis of TMAs. Further investigation into the contribution of tumour subtype stromal phenotype may further refine these findings.
我们旨在通过数字图像分析和机器学习算法来确定肿瘤基质比率(TSR)在管腔型和三阴性乳腺癌(TNBC)中的临床意义。使用QuPath软件进行自动图像分析,将其应用于一组647例乳腺癌患者(403例管腔型和244例TNBC),使用组织微阵列(TMA)的数字苏木精和伊红(H&E)图像。采用Kaplan-Meier法和Cox比例风险模型来确定与总生存期(OS)和乳腺癌特异性生存期(BCSS)的关系。对于TNBC,在多变量模型中,低TSR(高基质)与OS(风险比[HR] 1.9,置信区间[CI] 1.1 - 3.3,P = 0.021)和BCSS(HR 2.6,HR 1.3 - 5.4,P = 0.007)的不良预后相关,独立于年龄、大小、分级、肿瘤浸润淋巴细胞(sTILs)、淋巴结状态和化疗。然而,对于管腔型肿瘤,低TSR(高基质)在多变量分析中与OS的良好预后相关(HR 0.6,CI 0.4 - 0.8,P = 0.001),但与BCSS无关。TSR是TNBC中最重要的预后因素,但在管腔型乳腺癌中也是如此,并且可以通过对TMA进行定量图像分析来可靠地评估。对肿瘤亚型基质表型贡献的进一步研究可能会进一步完善这些发现。