Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO Porto), Research Center-LAB 3, F Bdg., 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
Department of Medical Oncology, Portuguese Institute of Oncology of Porto, Porto, Portugal.
Mol Med. 2020 Feb 12;26(1):22. doi: 10.1186/s10020-020-0147-5.
Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness.
H3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as 'low' or 'high' expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis.
The patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066-3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004-3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed (p = 0.069), reaching statistical significance in younger patients (p = 0.021).
H3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.
乳腺癌（BC）是一个重大的健康问题，更好地了解其生物学特性可能会改善治疗决策和患者预后。组蛋白 3 赖氨酸 27 三甲基化（H3K27me3）是一种常见的与基因表达改变相关的翻译后组蛋白修饰。在 BC 患者中，较低的 H3K27me3 表达与预后较差相关。我们使用数字成像软件评估了一组具有长期随访时间的 luminal 样 BC 患者的 H3K27me3 免疫表达，并评估了其与临床相关终点的相关性及其临床实用性。
通过数字成像系统评估 160 例 luminal A/B 样 HER2 阴性浸润性 BC（I-III 期）存档组织样本中的 H3K27me3 免疫表达。使用 Kaplan-Meier 和 Cox 回归进行生存分析。根据接收者操作特征（ROC）曲线分析定义的截止值，将病例分为“低”或“高”表达。
患者队列的中位年龄为 61 岁，中位随访时间为 11.7 年。低 H3K27me3 表达（低于 85%的截止值）与复发显著相关，无论是在单变量（HR=1.99，95%CI 1.066-3.724）还是在调整分级和年龄后的多变量分析中（HR=1.89，95%CI 1.004-3.559）。在低 H3K27me3 表达的 BC 中观察到死亡风险更高的趋势（p=0.069），在年轻患者中达到统计学意义（p=0.021）。
通过数字成像评分软件评估的 H3K27me3 免疫表达是 luminal 样 BC 患者的独立预后生物标志物，可辅助更个体化的辅助治疗决策，从而有可能降低治愈性治疗后的复发率，同时避免不必要的毒性。
