Abstract

Background: Gastroenteropancreatic neuroendocrine tumours (NETs) are uncommon tumours with a reported incidence of 2.5-5 per 100000 population. The recent classification system of NETs proposed by the European Neuroendocrine Tumour Society (ENETS) uses both Ki-67 labelling index and mitotic index to assign grade (low, intermediate, high). It has been adopted into routine practice but there is limited data on the relationship between these indices and their effect on classification. Aim: To identify the relationship between Ki-67 labelling index and mitotic count Methods: 160 NET patients, 81 midgut and 79 pancreatic had their cases reviewed. Ki-67 proliferation index, identified by staining tumour sections with MIB-1 antibody, was determined by assessing the percentage of positively staining tumour cell nuclei in 2000 tumour cells in areas with highest degree of nuclear labelling where possible. Mitotic counts (per 10 hpf) were evaluated in at least 40 fields in areas of highest mitotic activity. Grades (1 to 3) according to the new TNM classification were assigned using both indices. Correlation (Spearman r) and agreement (weighted Kappa) were calculated using Graphpad software. Results: 63 out of 81 midgut and 61 out of 79 pancreatic NETs had complete data. A highly significant correlation was observed between Ki-67 and mitotic count in both midgut (r=0.51, p<0.0001) and pancreatic (r=0.53, p<0.0001) NETs. When assigning tumour grade, there was only agreement in 67% of midgut and 44% of pancreatic NETs. Weighted Kappas for midgut (κ=0.35) and pancreatic (κ= 0.34) NETs only showed a ‘fair' measure of agreement between the two indices when assigning grade. Conclusion: This study suggests there may be a discrepancy when assigning grade of tumour in gastroenteropancreatic NETs based on Ki67 index and mitotic index. Although, as expected there is a high correlation between the 2 indices, when looking at agreement of assignment of grade, there is a discrepancy. This may have implications when proposing management strategies for patients.

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