Abstract
BackgroundThe Ki-67 index in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) may change throughout the disease course. However, the definitive effect of Ki-67 variability on GEP-NENs remains unknown. The aims of this study were to evaluate changes in Ki-67 levels throughout the disease course and investigate the role of Ki-67 index variability in GEP-NENs.MethodsSpecimens with multiple pathologies were evaluated from 30 patients who were selected from 514 patients with GEP-NENs, being treated at Wuhan Union Hospital from July 2009 to February 2018. The Ki-67 index was evaluated among multiple specimens over the disease course. Univariable and multivariable Cox proportional hazards regression analyses were performed to assess the prognostic significance of various clinical and histopathologic features.ResultsAmong the 514 patients with GEP-NENs, metastases were seen in 182 (35.41%). Among the 30 patients from whom specimens with multiple pathologies were obtained, 24 were both primary and metastatic specimens and six were specimens collected over the course of the disease. Changes in Ki-67 levels were detected in 53.3% of the patients, of whom 40% had up-regulated Ki-67 levels, and 13.3% had down-regulated Ki-67 levels. Kaplan–Meier survival analysis showed that the group with Ki-67 variability had a shorter overall survival (p = 0.0297). The Cox regression analysis indicated that Ki-67 variability (p = 0.038) was the only independent prognostic factor for overall survival.ConclusionsOur data suggest that patients with GEP-NENs and Ki-67 variability had a poorer prognosis. The re-assessment of Ki-67 at sites of metastasis or during the disease course might play a role in predicting the prognosis of patients with GEP-NENs. This finding could have implications for how GEP-NENs are monitored and treated.
Highlights
The Ki-67 index in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) may change throughout the disease course
Of the 514 GEP-NENs patients, 196 (38.13%) cases were of low grade grade 1 (G1); 102 (19.84%) of intermediate grade G2; and 216 (42.02%) of high grade grade 3 (G3)
We found that variability of the Ki-67 index between primary and metastatic specimens, or during the disease course was identified in about 53.3% of the patients in the present study
Summary
The Ki-67 index in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) may change throughout the disease course. The aims of this study were to evaluate changes in Ki-67 levels throughout the disease course and investigate the role of Ki-67 index variability in GEP-NENs. The Ki-67 protein, a cell proliferation-associated nuclear marker, has become a useful tool in assessing the malignant potential of neuroendocrine neoplasms (NENs) [1,2,3]. With respect to gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), the Ki-67 labeling index had already become an integral part of the World Health. Several publications have noted that the Ki-67 index varies from the site of the primary tumor to those of metastases, and even throughout the disease course [1, 2, 11]. Researchers have advocated that a sufficient evaluation of the Ki-67 index in metastatic tumors could have prognostic value and might be necessary to optimize clinical decision-making
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