海报库PosterKeep
PO.CL01.22 · 临床研究

原发性与转移性子宫内膜癌分子分型的不一致性：对精准治疗的意义

Discordance in molecular classification of primary and metastatic endometrial cancer: Implications for precision treatment

海报缩略图：原发性与转移性子宫内膜癌分子分型的不一致性：对精准治疗的意义
编号 1077 展板 17 时间 4/19 02:00–05:00 区域 Section 42 主讲 Mari Halle, MS;PhD
分会场 Circulating Tumor Cells, Metastasis, and Dissemination Biology 1
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作者与单位 Authors & Affiliations

Mari Kyllesø Halle1, Janka Babickova1, Hege Fredriksen Berg1, Erling Andre Hoivik2, Rose M. Gold1, Kadri Madissoo1, Marta Hjelmeland1, Hilde Eide Lien1, Jone Trovik3, Ingfrid S. Haldorsen4, Kathrine Woie5, Gema Moreno-Bueno6, Rameen Beroukhim7, Camilla Krakstad1

1Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway,2Gynecology & Obstretics, Haukeland University Hospital, Bergen, Norway,3Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway,4Department of Radiology, Haukeland University Hospital, Bergen, Norway,5Department of Obstetrics and Gynecology, Haukeland Univesity Hospital, Bergen, Norway,6Biochemistry Department, Universidad Autonoma de Madrid, Madrid, Spain,7Department of Cancer Biology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

摘要 Abstract

中文摘要
背景：子宫内膜癌是高收入国家最常见的妇科肿瘤，且发病率正在上升。通过POLE测序、错配修复（MMR）蛋白及p53免疫组化（IHC）进行的分子分型，在与现有风险模型整合后可提高预后判断的准确性。本研究探讨源自原发肿瘤活检（PBs）的分子分型是否在配对的转移灶活检（MBs）中得以保留，因为重新分型可能影响晚期及复发性疾病的治疗策略。 材料与方法：我们分析了155例具有配对PBs与MBs的患者。通过对第9、11、13和14外显子进行Sanger测序鉴定POLE突变。采用IHC评估MSH2、MSH6、PMS2、MLH1和p53的表达。对75例患者，全外显子组测序（WES）数据提供了PBs与MBs中POLE和TP53的突变谱。使用ProMisE算法对PBs与MBs分别进行分子分型，归入四个分子亚组。 结果：19%的病例中PBs与MBs之间的分子分型不一致。最常见的差异涉及MMR状态，其中10%（n = 16）在PBs中表现为MMR完整而在MBs中表现为缺陷。对于p53，9%（n = 20）在PBs中表现为异常表达而在MBs中为野生型。值得注意的是，在IHC检测的p53表达和WES检出的TP53突变中均观察到MB间异质性。所有POLE突变在PB-MB配对中均保持一致。基于MBs的分子分型与预后显著相关（p = 0.01），而基于PBs的分型则无相关性（p = 0.31）。 结论：这项全面的分子谱分析揭示了原发灶与转移灶之间分子分型的显著改变，尤其是在MMR和p53状态方面。这些变化具有预后意义，并强调了在转移灶活检中重新评估分子特征以指导晚期子宫内膜癌精准治疗策略的重要性。
查看英文原文 English abstract
Background: Endometrial cancer is the most prevalent gynecological cancer in high-income countries, and the incidence rate is increasing. Molecular classification with POLE sequencing and immunohistochemistry (IHC) for mismatch-repair (MMR) proteins and p53, refines prognostic accuracy when integrated with existing risk models. This study investigates whether molecular classification derived from primary tumor biopsies (PBs) is retained in matched metastatic biopsies (MBs), as reclassification may influence treatment strategies for advanced and recurrent disease. Material and methods: We analyzed 155 patients with matched PBs and MBs. POLE mutations were identified via Sanger sequencing of exons 9, 11, 13, and 14. IHC was used to assess expression of MSH2, MSH6, PMS2, MLH1, and p53. For 75 patients, whole-exome sequencing (WES) data provided mutational profiles for POLE and TP53 in both PBs and MBs. Molecular classification was assigned using the ProMisE algorithm to separately classify PBs and MBs in four molecular groups. Results: Molecular classification was discordant between PBs and MBs in 19% of cases. The most frequent discrepancy involved MMR status, with 10% (n = 16) showing MMR proficiency in PBs and deficiency in MBs. For p53, 9% (n = 20) had aberrant expression in PBs but wildtype in MBs. Notably, inter-MB heterogeneity was observed in both IHC-detected p53 expression and WES-derived TP53 mutations. All POLE mutations were conserved across PB-MB pairs. Molecular classification based on MBs was significantly associated with prognosis (p = 0.01), whereas classification from PBs was not (p = 0.31). Conclusions: This comprehensive molecular profiling reveals substantial shifts in molecular classification between primary and metastatic lesions, particularly in MMR and p53 status. These changes have prognostic implications and underscore the importance of reassessing molecular features in metastatic biopsies to guide precision treatment strategies for advanced endometrial cancer.
利益披露 Disclosure
M. K. Halle, None.. J. Babickova, None.. H. F. Berg, None.. E. A. Hoivik, None.. R. M. Gold, None.. K. Madissoo, None.. M. Hjelmeland, None.. H. E. Lien, None.. J. Trovik, None.. I. S. Haldorsen, None.. K. Woie, None.. R. Beroukhim, None.. C. Krakstad, None.

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