病理分级的时空异质性在非转移性肾癌动态演进过程中的预后价值探索  

Exploring the prognostic value of spatiotemporal heterogeneity in pathological grading during the dynamic progression of non-metastatic renal cancer

作　　者：雷畅 葛思论 周烨 陈辉 王林辉 曲乐 Chang Lei;Silun Ge;Ye Zhou;Hui Chen;Linhui Wang;Le Qu(Department of Urology,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210000,China;Department of Urology,Changhai Hospital,Naval Medical University,Shanghai 200433,China;Department of Pathology,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210000,China)

机构地区：[1]南京大学医学院附属金陵医院泌尿外科,南京市210000 [2]海军军医大学第一附属医院(长海医院)泌尿外科 [3]南京大学医学院附属金陵医院病理科

出　　处：《中国肿瘤临床》2024年第17期902-908,共7页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:82173345、82373154);江苏省自然科学基金-杰出青年项目(编号:BK20200006)资助。

摘　　要：目的:探讨非转移性肾癌在潜伏性和侵袭性生长过程中病理分级的时空异质性特点及其与临床结局的相关性。方法:回顾性分析2003年1月至2023年12月期间于国内13家医疗中心接受手术治疗的316例肾癌伴局部复发患者和429例肾癌伴静脉癌栓患者的病例资料,分别选取肾癌原发灶与复发灶、原发灶与癌栓组织之间的病理分级差异,作为肾癌动态演进过程中时空异质性的应用场景,并将病理分级变化定义为一种新的四分级方案(升级、降级、稳定低级别和稳定高级别):稳定低级别或稳定高级别是指肿瘤原发灶和癌栓/复发灶均表现为低级别(WHO/ISUPⅠ级或Ⅱ级)或高级别(WHO/ISUPⅢ级或Ⅳ级)。升级是指原发灶为低级别,癌栓/复发灶为高级别;相反,降级是指原发灶为高级别,癌栓/复发灶为低级别。分析病理分级变化的潜在影响因素及其对患者预后的影响。结果:肾癌伴静脉癌栓患者和肾癌伴局部复发患者的中位癌症特异性生存期(cancer-specific survival,CSS)分别为83个月和76个月,5年CSS率分别为65.6%和60.6%。分别有38.0%和43.6%的患者原发灶与癌栓、原发灶与复发灶的病理分级存在变化。Lasso-Logistic回归分析显示原发肿瘤坏死与病理分级变化密切相关。Kaplan-Meier生存曲线显示病理分级变化与患者预后显著相关,将Leibovich评分、UISS评分和GRANT评分中的病理分级替换为病理分级变化后,模型的预测效能得到显著提升,差异具有统计学意义(P<0.05)。结论:在非转移性肾癌动态演进过程中,存在病理分级的时空异质性。相对于孤立事件的病理分级,病理分级的时空变化是预测肾癌伴静脉癌栓患者和肾癌伴局部复发患者预后更准确的独立影响因素,纳入病理分级变化可显著提高既往预后模型的预测效能。Objective:To investigate the characteristics of spatiotemporal heterogeneity in pathological grading during the latent and invasive growth phases of non-metastatic renal cell carcinoma(RCC)and its correlation with clinical outcomes.Methods:A retrospective analysis was conducted on the case data of 316 RCC patients with local recurrence(LR)and 429 RCC patients with venous tumor thrombus(VTT)who underwent surgical treatment at 13 medical centers in China from January 2003 to December 2023.Pathological grade differences between primary tumor(PT)and LR,and between PT and VTT were selected as scenarios for the application of spatiotemporal heterogeneity in the dynamic progression of RCC.Pathological grading changes were defined according to a new four-tier scheme(upgrading,downgrading,stable low-grade,and stable high-grade).Stable low-or high-grade was defined as low-grade(WHO/ISUP grade Ⅰ or Ⅱ)or highgrade(WHO/ISUP grade Ⅲ or Ⅳ)in both PT and LR/VTT.Upgrading was defined as low-grade in the PT and high-grade in the LR/VTT;conversely,downgrading was defined as high-grade in the PT and low-grade in the LR/VTT.The potential influencing factors of pathological grading changes and their impact on patient prognosis were analyzed.Results:The median cancer-specific survival(CSS)for RCC patients with VTT and RCC patients with LR was 83 months and 76 months,respectively.The 5-year CSS rates were 65.6%and 60.6%,respectively.Pathological grading changes were observed in 38.0% of patients with PT and VTT and in 43.6% of patients with PT and LR.Lasso-Logistic regression analysis revealed a close correlation between primary tumor necrosis and pathological grading changes.Kaplan-Meier survival curves indicated a significant correlation between pathological grading changes and prognosis.Replacing the pathological grading in Leibovich,UISS,and GRANT scores with pathological grading changes significantly improved the predictive performance of the models(P<0.05).Conclusions:Spatiotemporal heterogeneity in pathological grading ex

关 键 词：肾细胞癌 时空异质性 静脉癌栓 局部复发 预后模型 

分 类 号：R737.11[医药卫生—肿瘤]