Department of Obstetrics and Gynaecology, University of Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany.
Department of Pathology, University of Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Arch Gynecol Obstet. 2024 Apr;309(4):1525-1533. doi: 10.1007/s00404-023-07225-z. Epub 2023 Oct 30.
Androgen receptor (AR) can serve as a new therapeutic target since it was shown to play a proliferative role in several breast cancer (BC) subtypes. Moreover, AR positivity has been suggested to reflect the metastatic potential of tumor cells in some BC subtypes. The aim of this study was to determine the AR expression on disseminated tumor cells (DTCs) as a surrogate marker of minimal residual disease (MRD) and potential precursor of metastasis in early BC.
Bone marrow (BM) aspirates from 62 DTC-positive early BC patients were included into this study and analyzed by immunofluorescence staining for the presence of AR-positive DTCs. CK-positive, CD45-negative cells containing an intact nucleus (DAPI positive) were identified as DTCs. AR expression of the primary tumor (PT) was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tumor sections from core biopsies and surgical specimens.
AR status of DTCs could be determined in 21 patients. We detected AR-positive DTCs in nine samples (43%). AR expression of DTCs and corresponding PT showed a concordance rate of 33%. The DTC-AR status did not correlate with clinicopathological factors, nor did we observe a significant correlation between the AR status of the PT and other established prognostic factors for BC.
AR-positive DTCs can be detected in BM of early BC patients with a marked discordance of the AR status between DTCs and corresponding PTs. The clinical significance of these findings needs further investigation.
由于雄激素受体 (AR) 在几种乳腺癌 (BC) 亚型中发挥增殖作用,因此它可以作为新的治疗靶点。此外,AR 阳性已被认为反映了某些 BC 亚型肿瘤细胞的转移潜能。本研究旨在确定播散性肿瘤细胞 (DTC) 中的 AR 表达作为微小残留病 (MRD) 的替代标志物,并作为早期 BC 中转移的潜在前体。
本研究纳入了 62 例 DTC 阳性早期 BC 患者的骨髓 (BM) 抽吸物,并通过免疫荧光染色分析 AR 阳性 DTC 的存在。含有完整细胞核 (DAPI 阳性) 的 CK 阳性、CD45 阴性细胞被鉴定为 DTC。通过对核心活检和手术标本的福尔马林固定、石蜡包埋 (FFPE) 肿瘤切片进行免疫组织化学评估 PT 中 AR 的表达。
可在 21 例患者中确定 DTC 的 AR 状态。我们在九个样本(43%)中检测到 AR 阳性 DTC。DTC-AR 状态与临床病理因素无相关性,也未观察到 PT 中 AR 状态与其他已确立的 BC 预后因素之间存在显著相关性。
可以在早期 BC 患者的 BM 中检测到 AR 阳性 DTC,DTC 和相应的 PT 之间的 AR 状态存在明显差异。这些发现的临床意义需要进一步研究。