An increase in the Ki-67 index in neuroendocrine neoplasms over time in relation to prognosis has scarcely been investigated. We aimed to assess whether the Ki-67 index changed over time and also whether a change influenced prognosis. Second, we investigated the difference in the Ki-67 index between primary tumour and metastases. From 1 January 1995 to 31 December 2019, 108 consecutive patients with gastroenteropancreatic tumours were included. Patients were followed with regard to an increase in the Ki-67 index and all-cause mortality. Ki-67 determination of the primary tumour at diagnosis and at the time of radiological progression, including developed metastases, was performed. A significant increase in the Ki-67 index was defined as a doubling of the value at disease progression compared to the value at diagnosis. In addition, in 14 patients, the Ki-67 index of the primary tumour and present metastases at the time of diagnosis was investigated. At diagnosis, there were no differences in the Ki-67 index between primary tumours and metastases (P = .41). Sixty-five patients had a doubling of the Ki-67 index. The median Ki-67 index at the time of progression 17% (1%-90%) vs 5% (1%-60%) at the time of diagnosis (P = .006). A doubling of the Ki-67 index was independently associated with all-cause mortality (hazard ratio = 2.7 [1.3-6.3], P = 0.02), after adjustment for relevant co-variables including the Ki-67 index at baseline. Doubling of the Ki-67 index at the time of disease progression was associated with a significantly higher risk of all-cause mortality. We recommend that a Ki-67 index is obtained whenever disease progression is recorded by demonstrated progression because it may have impact on the choice of treatment.

中文翻译：

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神经内分泌肿瘤患者Ki-67指数升高及对死亡率的影响

几乎没有研究过神经内分泌肿瘤中 Ki-67 指数随时间增加与预后的关系。我们旨在评估 Ki-67 指数是否随时间变化以及变化是否影响预后。其次，我们研究了原发肿瘤和转移瘤之间 Ki-67 指数的差异。1995年1月1日至2019年12月31日，连续纳入108例胃肠胰腺肿瘤患者。随访患者 Ki-67 指数和全因死亡率的增加。在诊断和放射学进展（包括发生转移）时对原发肿瘤进行 Ki-67 测定。Ki-67 指数的显着增加被定义为疾病进展时的值与诊断时的值相比翻了一番。此外，在 14 名患者中，研究了诊断时原发肿瘤和现有转移的 Ki-67 指数。在诊断时，原发肿瘤和转移瘤之间的 Ki-67 指数没有差异。P  = .41）。65 名患者的 Ki-67 指数翻了一番。进展时的中位 Ki-67 指数为 17% (1%-90%) 与诊断时的 5% (1%-60%) ( P  = .006)。 在调整包括基线 Ki-67 指数在内的相关协变量后，Ki-67 指数翻倍与全因死亡率独立相关（风险比 = 2.7 [1.3-6.3]，P = 0.02）。疾病进展时 Ki-67 指数加倍与全因死亡风险显着升高相关。我们建议在通过证明的进展记录疾病进展时获得 Ki-67 指数，因为它可能会影响治疗的选择。