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雄激素受体(AR)在子宫内膜癌侵袭性中的作用:与其他预后标志物的相关性及治疗意义。一项回顾性观察性研究

英文原题:The role of the Androgen Receptor (AR) in endometrial cancer aggressiveness: Correlation with other prognostic markers and therapeutic implications. A retrospective observational study.

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The role of the Androgen Receptor (AR) in endometrial cancer aggressiveness: Correlation with other prognostic markers and therapeutic implications. A retrospective observational study.

PubMed 2025/03/31(内容时间) Pathol Res Pract Q1 · IF 3.7(JCR 2025)

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中文摘要

子宫内膜癌(EC)是最常见的妇科恶性肿瘤,其发病率不断上升,与风险因素的增加有关。这项回顾性观察性研究探讨了雄激素受体(AR)在EC侵袭性中的作用、其与其他预后标志物的相关性及其潜在的治疗意义。共分析了143例接受子宫切除术治疗的EC病例,检测AR表达及其与临床病理和分子标志物的关联,包括雌激素受体(ER)、孕激素受体(PR)、Ki-67、p53、β-catenin、E-cadherin、Bcl-2、Cyclin D1和错配修复(MMR)状态。AR表达在低级别子宫内膜样癌(LGEC)中显著高于高级别子宫内膜样癌(HGEC)和其他高风险组织学类型(p = 0.015),提示其在侵袭性较低的肿瘤表型中发挥作用。AR与ER和PR强相关(p < 0.0001),表明存在共享的调控通路。与TIL(肿瘤浸润淋巴细胞)(TILs)的临界关联提示其可能在免疫应答中发挥作用。

然而,AR表达与增殖标志物(Ki-67)或肿瘤抑制标志物(p53)无显著相关性,与β-catenin、E-cadherin、Bcl-2、Cyclin D1或MMR状态也无显著相关性。这些发现支持AR作为激素反应性EC亚型的预后标志物,并提示AR靶向治疗可能有益,尤其是在ER/PR阴性肿瘤中。

该研究强调了将AR状态纳入分子分型的潜在价值,有助于制定个性化治疗策略以改善EC管理中的患者预后。

展开英文摘要原文

Endometrial carcinoma (EC) is the most common gynecological malignancy, with increasing incidence linked to rising risk factors. This retrospective observational study investigates the role of the Androgen Receptor (AR) in EC aggressiveness, its correlation with other prognostic markers, and its potential therapeutic implications. A total of 143 cases of EC treated with hysterectomy were analyzed for AR expression and its association with clinicopathological and molecular markers, including estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, β-catenin, E-cadherin, Bcl-2, Cyclin D1, and mismatch repair (MMR) status.

AR expression was significantly higher in low-grade endometrioid carcinoma (LGEC) compared to high-grade endometrioid carcinoma (HGEC) and other high-risk histologies (p = 0. 015), suggesting a role in less aggressive tumor phenotypes. AR strongly correlated with ER and PR (p < 0. 0001), indicating shared regulatory pathways. A borderline association with tumor-infiltrating lymphocytes (TILs) suggests a potential role in immune response.

However, AR expression did not significantly correlate with markers of proliferation (Ki-67) or tumor suppression (p53), nor with β-catenin, E-cadherin, Bcl-2, Cyclin D1, or MMR status.

These findings support AR as a prognostic marker in hormone-responsive EC subtypes and suggest that AR-targeted therapies could be beneficial, particularly in ER/PR-negative tumors. The study highlights the potential integration of AR status into molecular profiling, aiding in personalized treatment strategies for improved patient outcomes in EC management.

论文信息

作者
Paudice M、Greppi M、Valle L、Piol N、Barra F、Mammoliti S、Ferrero S、Marcenaro E
第一作者单位
Department of Integrated Diagnostic and Surgical Sciences (DISC), University of Genoa, Genoa 16132, Italy; Pathology University Unit, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy.Italy
通讯作者单位
Department of Integrated Diagnostic and Surgical Sciences (DISC), University of Genoa, Genoa 16132, Italy; Pathology Unit, IRCCS Istituto Giannina Gaslini, Genoa 16147, Italy. Electronic address: valeriovellone@gaslini.org.Italy
文献类型
观察性研究
期刊
Pathology, research and practice2025 May
原文标识
PubMed 40186889 · DOI 10.1016/j.prp.2025.155922