Increase of Ki-67 index and influence on mortality in patients with neuroendocrine neoplasms.

Abstract

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.