Capozzi Vito Andrea, Perrone Emanuele, Scarpelli Elisa, Tarantino Vincenzo, Giuliano Maria Consiglia, Carnelli Marco, De Iaco Pierandrea, Perrone Anna Myriam, Puppo Andrea, Bogani Giorgio, Ceccaroni Marcello, Chiantera Vito, Cucinella Giuseppe, Uccella Stefano, Scambia Giovanni, Fanfani Francesco, Berretta Roberto
Department of Gynecology and Obstetrics, University Hospital of Parma, Italy.
Department of Women, Children and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Eur J Cancer. 2025 Jul 25;225:115586. doi: 10.1016/j.ejca.2025.115586. Epub 2025 Jun 18.
Endometrial cancer (EC) management includes nodal staging and molecular classification. Despite molecular advancements, the biological significance of isolated tumor cells (ITC) in EC remains unclear. This study aimed to characterize ITC in the context of pathological and molecular features MATERIALS AND METHODS: A multicenter, retrospective analysis included EC patients diagnosed between June 2018 and May 2024 who underwent surgical staging via sentinel lymph node (SLN) biopsy and molecular profiling. ITC cases detected through SLN ultrastaging or One Step Nucleic Acid Amplification (OSNA) were compared with N0 and N + (micro-/macrometastasis) groups.
Among the 1821 patients included, nodal status was N0 in 84.5 %, ITC in 5.1 %, micrometastases in 5.3 %, and macrometastases in 4.5 %. ITC patients exhibited deep myometrial invasion in 67.7 % of cases vs. 28.7 % in N0 (p < 0.001). Diffuse lymphovascular space invasion (LVSI) was significantly higher in ITC (52.1 %) than N0 (12.2 %, p < 0.001). MMR deficiency was more frequent in ITC (33.3 %) vs. N0 (25.0 %, p = 0.07). POLE mutations were more common in N0 (4.2 %) and ITC (3.1 %) vs. N + (1.1 %), though not statistically significant. p53-abnormal tumors were significantly associated with N + status (19.4 %) compared to ITC (7.3 %, OR 0.33, p = 0.008). No relapses occurred among ITC patients with low-risk features.
These findings suggest that ITC may represent an early form of nodal involvement, biologically distinct from micro- and macrometastases. The association with MMR deficiency and the absence of aggressive markers such as p53 abnormalities support a less aggressive profile. Integrating molecular and pathological features may refine risk stratification and inform management strategies for EC patients with ITC.
子宫内膜癌（EC）的治疗包括淋巴结分期和分子分类。尽管在分子研究方面取得了进展，但EC中孤立肿瘤细胞（ITC）的生物学意义仍不清楚。本研究旨在根据病理和分子特征对ITC进行特征描述。
一项多中心回顾性分析纳入了2018年6月至2024年5月期间诊断为EC且通过前哨淋巴结（SLN）活检进行手术分期和分子分析的患者。将通过SLN超分期或一步核酸扩增（OSNA）检测到的ITC病例与N0和N +（微转移/宏转移）组进行比较。
在纳入的1821例患者中，淋巴结状态为N0的占84.5%，ITC的占5.1%，微转移的占5.3%，宏转移的占4.5%。ITC患者中67.7%的病例有子宫肌层深层浸润，而N0组为28.7%（p < 0.001）。ITC患者中弥漫性淋巴管间隙浸润（LVSI）显著高于N0组（52.1%对12.2%，p < 0.001）。ITC患者中错配修复缺陷（MMR）更常见（33.3%），高于N0组（25.0%，p = 0.07）。POLE突变在N0组（4.2%）和ITC组（3.1%）中比N +组（1.1%）更常见，尽管无统计学意义。与ITC组（7.3%，OR 0.33，p = 0.008）相比，p53异常肿瘤与N +状态显著相关（19.4%）。具有低风险特征的ITC患者未发生复发。
这些发现表明，ITC可能代表淋巴结受累的早期形式，在生物学上与微转移和宏转移不同。与MMR缺陷的关联以及缺乏p53异常等侵袭性标志物支持其侵袭性较低的特征。整合分子和病理特征可能会优化风险分层，并为ITC的EC患者提供管理策略依据。
