Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Breast Cancer Res Treat. 2023 Jul;200(2):293-304. doi: 10.1007/s10549-023-06974-4. Epub 2023 May 24.
Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer.
Dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34. Digital images of stainings were analyzed to extract quantitative data on vessel density, vessel size, and perivascular alpha-SMA status.
The analyses in the discovery cohort (n = 108) revealed a statistically significant relationship between large vessel size and shorter disease-specific survival (p = 0.007, log-rank test; p = 0.01, HR 3.1; 95% CI 1.3-7.4, Cox-regression analyses). Subset analyses indicated that the survival association of vessel size was strengthened in ER + breast cancer. To consolidate these findings, additional analyses were performed on a validation cohort (n = 267) where an association between large vessel size and reduced survival was also detected in ER + breast cancer (p = 0.016, log-rank test; p = 0.02; HR 2.3, 95% CI 1.1-4.7, Cox-regression analyses).
Alpha-SMA/CD34 dual-IHC staining revealed breast cancer heterogeneity regarding vessel size, vessel density, and perivascular a-SMA status. Large vessel size was linked to shorter survival in ER + breast cancer.
血管生成对于肿瘤生长至关重要,是癌症的标志之一。本研究分析了微血管密度、血管中值大小和血管周 a-SMA 表达作为乳腺癌的预后生物标志物。
进行双重免疫组化染色,使用 α-SMA 抗体与内皮细胞标志物 CD34 抗体一起使用。对染色的数字图像进行分析,以提取血管密度、血管大小和血管周 α-SMA 状态的定量数据。
在发现队列(n=108)中的分析显示,大血管大小与疾病特异性生存时间缩短之间存在统计学显著关系(p=0.007,对数秩检验;p=0.01,HR 3.1;95%CI 1.3-7.4,Cox 回归分析)。亚组分析表明,在 ER+乳腺癌中,血管大小与生存的相关性更强。为了巩固这些发现,在验证队列(n=267)中进行了额外的分析,其中在 ER+乳腺癌中也检测到大血管大小与生存降低之间的关联(p=0.016,对数秩检验;p=0.02;HR 2.3,95%CI 1.1-4.7,Cox 回归分析)。
α-SMA/CD34 双重免疫组化染色揭示了乳腺癌在血管大小、血管密度和血管周 a-SMA 状态方面的异质性。大血管大小与 ER+乳腺癌的生存时间缩短相关。