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雄激素受体过表达在三阴性乳腺癌中的双重功能:一个复杂的预后标志物

英文原题:Dual Functions of Androgen Receptor Overexpression in Triple-Negative Breast Cancer: A Complex Prognostic Marker.

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Dual Functions of Androgen Receptor Overexpression in Triple-Negative Breast Cancer: A Complex Prognostic Marker.

PubMed 2025/01/10(内容时间) Bioengineering (Basel) Q2 · IF 4.4(JCR 2025)

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中文摘要

一部分三阴性乳腺癌(TNBC)表达雄激素受体(AR),但AR阳性的阈值及其临床意义存在差异。我们假设客观评估优于主观方法,并且高AR对预后产生负面影响。在一个基于人群的TNBC队列(n = 198)中,随访时间较长(4-383个月),通过主观评分(AR-Manual)和自动数字图像分析(AR-DIA)评估AR表达。通过AR-DIA确定的10% cut-off值是远处转移的最强负向预后阈值(p = 0.008)。高AR-DIA与较低分级(p = 0.014)和较低增殖(p = 0.004)相关,但也与较大肿瘤(p = 0.047)、远处转移(p = 0.052)和淋巴结(LN)阳性(p < 0.001)相关,突显了其双重作用。多变量分析显示,LN状态与AR-DIA之间的交互作用(p < 0.001)是最强的预后因素,其次是纤维化灶(FF;p = 0.009)、核分裂活性指数(MAI;p = 0.018)和间质TIL(肿瘤浸润淋巴细胞)(sTILs;p = 0.041)。AR-DIA在有利亚组中没有额外预后价值,但在不利亚组中显著。在高AR-DIA且具有不利特征的患者中,ACT并未改善生存,患者可能从AR靶向治疗中获益。

总体而言,DIA方法提供了可重复性,高AR-DIA(≥10%)在不同TNBC亚组中显示出相反的生存效应,AR评估对预后和AR靶向治疗至关重要。

展开英文摘要原文

A subset of triple-negative breast cancer (TNBC) expresses the androgen receptor (AR), but thresholds for AR positivity and its clinical significance vary.

We hypothesize that objective assessment outperforms subjective methods, and that high AR negatively impacts prognosis. In a population-based TNBC cohort ( n = 198) with long follow-up (4-383 months), AR expression was evaluated via subjective scoring (AR-Manual) and automated digital image analysis (AR-DIA). A 10% cut-off value via AR-DIA was the strongest negative prognostic threshold for distant metastases ( p = 0. 008). High AR-DIA correlated with lower grade ( p = 0. 014), and lower proliferation ( p = 0. 004) but also with larger tumors ( p = 0. 047), distant metastasis ( p = 0.

052), and lymph node (LN) positivity ( p < 0. 001), highlighting its dual roles. Multivariate analysis revealed interaction between LN status and AR-DIA ( p < 0. 001) as the strongest prognostic factor, followed by fibrotic focus (FF; p = 0. 009), mitotic activity index (MAI; p = 0.

018), and stromal tumor-infiltrating lymphocytes (sTILs; p = 0. 041). AR-DIA had no additional prognostic value in favorable subgroups but was significant in unfavorable subgroups. In high AR-DIA patients with unfavorable characteristics, ACT did not improve survival, and patients may benefit from AR-targeted therapy.

Overall, the DIA method provides reproducibility, high AR-DIA (≥10%) shows opposing survival effects in different TNBC subgroups, and AR evaluation is crucial for prognosis and AR-targeted therapies.

论文信息

作者
Kiraz U、Rewcastle E、Fykse SK、Lundal I、Gudlaugsson EG、Skaland I、Søiland H、Baak JPA
单位
Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway.Norway
期刊
Bioengineering (Basel, Switzerland)2025 Jan 10
原文标识
PubMed 39851328 · DOI 10.3390/bioengineering12010054