Longitudinal Changes in Ki-67 Indices in Small-Intestinal Neuroendocrine Tumours and Their Impact on Survival.

IF 3.2 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Neuroendocrinology Pub Date : 2024-08-27 DOI:10.1159/000541101

Kosmas Daskalakis, Marina Tsoli, Maria Wedin, Beata Kos-Kudla, Angelika Kogut, Raj Srirajaskanthan, D S V M Clement, Georgios Giovos, Martin O Weickert, Gregory Kaltsas

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引用次数: 0

Abstract

Introduction: The purpose of this study was to evaluate longitudinal changes in Ki-67 indices of SI-NETs and assess the impact of these in overall survival (OS).

Methods: We screened 551 patients with SI-NETs diagnosed from 1993, through 2021, identified using the SI-NET databases from five European referral centres. Only patients with well-differentiated tumours and available baseline tumour samples, and follow-up re-biopsies were included. For tumour grading, apart from 2017 WHO classification system, we applied a recently proposed SI-NET site-specific modified histopathological grading system with Ki-67 cut-offs of 5 and 10%.

Results: We included 45 patients. Median Ki-67 index at SI-NET diagnosis was 2% (range 0.5-15%). Thirty-three patients had Ki67 indices <5% (70.2%), 6 had Ki67: 5-10% (12.8%) and 8 had Ki67 ≥10% (17%). Mean time to re-biopsy was 48.8 months (SD: +/-162.5). At re-biopsy, the median change in Ki-67 index (absolute value; follow-up minus time of diagnosis) was 1% (range -10 to +38%). An increase in Ki-67 occurred in 20 patients (42.6%); in 14 patients the change in Ki-67 resulted in progression to higher tumour grade following the modified grading system. Patients with an increment in Ki-67≥1% had a median OS of 32.9 months vs. 80.5 months in patients without (HR 5.6, 95% CI: 1.42-22.02, p=0.014). When applying the novel modified histopathological grading system for SI-NETs, patients with grade progression had a median OS of 32.9 months vs. 53.7 months in those without (HR=4.61, 95%CI: 1.22-13.54; p=0.022). At multivariable analysis, grade progression was confirmed as an independent predictor for death (HR=7.2, 95%CI: 1.58-32.82; p=0.011).

Conclusions: Metachronous increment in Ki-67 indices and related grade progression over time following a site-specific modified histopathological grading system with Ki-67 cut-offs of 5 and 10% is observed in approximately 1/3 of SI-NETs included in this study and it is associated with worse survival outcomes.

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小肠神经内分泌肿瘤 Ki-67 指数的纵向变化及其对生存期的影响

简介：本研究旨在评估SI-NET的Ki-67指数的纵向变化，并评估这些变化对总生存率（OS）的影响：本研究旨在评估SI-NET的Ki-67指数的纵向变化，并评估这些变化对总生存率（OS）的影响：我们筛选了从1993年到2021年确诊的551例SI-NET患者，这些患者是通过欧洲5个转诊中心的SI-NET数据库确定的。只有肿瘤分化良好、有基线肿瘤样本和随访再活检样本的患者才被纳入。在肿瘤分级方面，除2017年世界卫生组织分类系统外，我们还采用了最近提出的SI-NET特定部位改良组织病理学分级系统，Ki-67临界值分别为5%和10%：我们共纳入了45名患者。SI-NET诊断时的Ki-67指数中位数为2%（范围为0.5-15%）。33例患者的Ki67指数为5%（70.2%），6例患者的Ki67指数为5%-10%（12.8%），8例患者的Ki67指数≥10%（17%）。再次活组织检查的平均时间为48.8个月（SD：+/-162.5）。再次活组织检查时，Ki-67指数（绝对值；随访时间减去诊断时间）的中位数变化为1%（范围为-10%至+38%）。20名患者（42.6%）的Ki-67指数出现了上升；14名患者的Ki-67指数变化导致其肿瘤分级升高（根据修改后的分级系统）。Ki-67增高≥1%的患者的中位OS为32.9个月，而未增高的患者为80.5个月（HR 5.6，95% CI：1.42-22.02，P=0.014）。当采用新的改良组织病理学分级系统对SI-NETs进行分级时，分级进展患者的中位OS为32.9个月，而未分级进展患者的中位OS为53.7个月（HR=4.61，95%CI：1.22-13.54；P=0.022）。多变量分析证实，分级进展是死亡的独立预测因素（HR=7.2，95%CI：1.58-32.82；P=0.011）：本研究中约有1/3的SI-NET观察到Ki-67指数随着时间的推移而同步增加，相关的分级也随之进展，Ki-67的临界值为5%和10%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroendocrinology 医学-内分泌学与代谢

CiteScore

8.30

自引率

2.40%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.