肿瘤相关基质细胞密度作为乳腺癌复发和死亡的预测指标：来自不同种族研究人群的结果。
Tumor-Associated Stromal Cellular Density as a Predictor of Recurrence and Mortality in Breast Cancer: Results from Ethnically Diverse Study Populations.
机构信息
Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Cancer Epidemiol Biomarkers Prev. 2021 Jul;30(7):1397-1407. doi: 10.1158/1055-9965.EPI-21-0055. Epub 2021 May 5.
PURPOSE
Tumor-associated stroma is comprised of fibroblasts, tumor-infiltrating lymphocytes (TIL), macrophages, endothelial cells, and other cells that interactively influence tumor progression through inflammation and wound repair. Although gene-expression signatures reflecting wound repair predict breast cancer survival, it is unclear whether combined density of tumor-associated stromal cells, a morphologic proxy for inflammation and wound repair signatures on routine hematoxylin and eosin (H&E)-stained sections, is of prognostic relevance.
METHODS
By applying machine learning to digitized H&E-stained sections for 2,084 breast cancer patients from China ( = 596; 24-55 years), Poland ( = 810; 31-75 years), and the United States ( = 678; 55-78 years), we characterized tumor-associated stromal cellular density (SCD) as the percentage of tumor-stroma that is occupied by nucleated cells. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between SCD and clinical outcomes [recurrence (China) and mortality (Poland and the United States)] were estimated using Cox proportional hazard regression, adjusted for clinical variables.
RESULTS
SCD was independently predictive of poor clinical outcomes in hormone receptor-positive (luminal) tumors from China [multivariable HR (95% CI) = 1.86 (1.06-3.26); = 0.03], Poland [HR (95% CI) = 1.80 (1.12-2.89); = 0.01], and the United States [HR (95% CI) = 2.42 (1.33-4.42); = 0.002]. In general, SCD provided more prognostic information than most classic clinicopathologic factors, including grade, size, PR, HER2, IHC4, and TILs, predicting clinical outcomes irrespective of menopausal or lymph nodal status. SCD was not predictive of outcomes in hormone receptor-negative tumors.
CONCLUSIONS
Our findings support the independent prognostic value of tumor-associated SCD among ethnically diverse luminal breast cancer patients.
IMPACT
Assessment of tumor-associated SCD on standard H&E could help refine prognostic assessment and therapeutic decision making in luminal breast cancer.
目的
肿瘤相关基质由成纤维细胞、肿瘤浸润淋巴细胞（TIL）、巨噬细胞、内皮细胞和其他细胞组成，它们通过炎症和伤口修复相互作用影响肿瘤的进展。虽然反映伤口修复的基因表达特征可以预测乳腺癌的生存，但尚不清楚常规苏木精和伊红（H&E）染色切片上肿瘤相关基质细胞的密度（作为炎症和伤口修复特征的形态学替代物）是否具有预后相关性。
方法
通过对来自中国（n=596；24-55 岁）、波兰（n=810；31-75 岁）和美国（n=678；55-78 岁）的 2084 例乳腺癌患者的数字化 H&E 染色切片应用机器学习，我们将肿瘤相关基质细胞密度（SCD）定义为核细胞占据的肿瘤基质百分比。使用 Cox 比例风险回归估计 SCD 与临床结局（中国的复发；波兰和美国的死亡率）之间的关联的风险比（HR）和 95%置信区间（CI），并根据临床变量进行调整。
结果
SCD 独立预测中国激素受体阳性（管腔）肿瘤的不良临床结局[多变量 HR（95%CI）=1.86（1.06-3.26）；P=0.03]、波兰[HR（95%CI）=1.80（1.12-2.89）；P=0.01]和美国[HR（95%CI）=2.42（1.33-4.42）；P=0.002]。总体而言，SCD 提供了比大多数经典临床病理因素更多的预后信息，包括分级、大小、PR、HER2、IHC4 和 TILs，无论绝经或淋巴结状态如何，均可预测临床结局。SCD 对激素受体阴性肿瘤的结局没有预测作用。
结论
我们的研究结果支持在不同种族的管腔乳腺癌患者中，肿瘤相关 SCD 具有独立的预后价值。
影响
在标准 H&E 上评估肿瘤相关 SCD 可能有助于细化管腔乳腺癌的预后评估和治疗决策。
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