肥胖与癌症：一项转化科学综述
Obesity and Cancer: A Translational Science Review.
超重和肥胖与更高的癌症发病率相关，在美国每年占新发癌症诊断的 10%。减重可能通过减轻肥胖的不良影响来降低癌症风险，但可能需要减重超过 10% 才能降低癌症风险。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于 MMR 缺失机制的错配修复缺陷子宫内膜癌亚分层可提供预后和预测的精细化
英文原题：Substratification of mismatch repair deficient endometrial cancers based on mechanism of MMR loss can provide prognostic and predictive refinement.
查看英文原题
Substratification of mismatch repair deficient endometrial cancers based on mechanism of MMR loss can provide prognostic and predictive refinement.
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研究概要
MLH1 缺失识别出 MMRd EC 中预后更差且 CD8+密度更低的一个亚群，支持对该分子亚型进行进一步分层。在 MMRd EC 中，分级、组织学类型、ER、PR、L1CAM、CTNNB1 和 p53 状态并未增加预后细化的价值。
研究思路结论见上方概要
背景
错配修复缺陷（MMRd）子宫内膜癌（EC）占EC的25-30%。识别MMRd可指导Lynch综合征检测和免疫检查点抑制剂（ICI）治疗。我们的目的是描述在ICI时代之前接受治疗的MMRd EC的临床病理和分子特征。
方法
MMRd ECs被回顾性识别，肿瘤接受了选择性免疫组化及热点 panel 测序。
结果
MMRd ECs（n = 899）主要為 FIGO 2009 I 期（77%）、子宮內膜樣組織型（92%），14% 有淋巴結轉移（LNM）。淋巴血管浸潤和肌層浸潤在 MMRd ECs 中具有預後意義，但分級和組織型則無。與 MSH2/MSH6/孤立性 PMS2 缺失（20%）患者相比，MLH1 缺失（80%）患者年齡更大、BMI 更高、腫瘤浸潤更深且 LNM 更多。MLH1 缺失患者預後更差；18% 患者復發，10% 死於疾病，而 MSH2/MSH6/孤立性 PMS2 缺失患者分別為 7% 和 4%。MLH1 缺失腫瘤具有較低的 CD8+ 腫瘤浸潤淋巴細胞密度，這與更差的預後相關。ER、PR、L1CAM 和 CTNNB1 與 MMRd ECs 的結局無關。MMRd-p53abn（N = 150，多分類器）患者與 p53 表達野生型 MMRd ECs 患者之間的結局無差異。對於 ESMO 高風險或高/晚期/轉移風險組合組，化放療與單純放療的結局相同。
展开英文摘要原文
BACKGROUND
Mismatch repair deficient (MMRd) endometrial carcinomas (EC) encompass 25-30% of ECs. Identifying MMRd directs Lynch Syndrome testing and immune checkpoint inhibitor (ICI) therapy. Our aim was to characterize the clinicopathologic and molecular features of MMRd ECs treated in the pre-ICI era.
METHODS
MMRd ECs were identified retrospectively and tumors underwent selective immunohistochemistry and hotspot panel sequencing.
RESULTS
MMRd ECs (n = 899) were predominantly FIGO 2009 stage I (77%), endometrioid histotype (92%), with 14% lymph node metastases (LNM). Lymphovascular invasion and myoinvasion were prognostic in MMRd ECs, but grade and histotype were not. Patients with MLH1 loss (80%) were older with higher BMI, had more deeply invasive tumors and more LNM compared to patients with MSH2/MSH6/isolated PMS2 loss (20%). Worse outcomes were observed with MLH1 loss; 18% of patients recurred and 10% died of disease compared to 7% and 4% with MSH2/MSH6/isolated PMS2 loss. MLH1 loss tumors had lower CD8+ tumor infiltrating lymphocyte densities, which were associated with worse prognosis. ER, PR, L1CAM and CTNNB1 were not associated with outcomes in MMRd ECs. There was no difference in outcomes between patients with MMRd-p53abn (N = 150, multiple classifiers) and MMRd ECs with wildtype p53 expression. Outcomes were identical for chemoradiation vs radiation alone for ESMO high risk or high/advanced/metastatic risk groups combined.
CONCLUSION
MLH1 loss identifies a subset of MMRd ECs with worse outcomes and lower CD8+ densities supporting substratification of this molecular subtype. Grade, histotype, ER, PR, L1CAM, CTNNB1 and p53 status do not add prognostic refinement within MMRd EC.
论文信息
- 作者
- Jamieson A、Rogan S、Zhang AW、Martin SD、Leung S、Chiu D、McRae K、Mah SJ
- 第一作者单位
- Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, Canada.Canada
- 通讯作者单位
- Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, Canada. Electronic address: jessica.mcalpine@vch.ca.Canada
- 文献类型
- 非美国政府资助研究
- 期刊
- Gynecologic oncology2026 Feb
- 原文标识
- PubMed 41592518 · DOI 10.1016/j.ygyno.2026.01.233