New diagnostic histopathological approach in the evaluation of Ki-67 in GEP-NETs

Abstract Introduction: Many studies over the past decade have shown that the Ki-67 index is a valuable biomarker for the diagnosis, classification of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs).In the present work, therefore, we have decided to evaluate the expression of Ki-67 based on the intensity of the stain, basing our hypothesis on the fact that the Ki-67 protein is continuously degraded during G0 and G1 and the production constantly increases from the start of the S phase until mitotic exit and therefore the longer a cell has spent hibernating, the lower its Ki-67 level will be when it re-enters the cell cycle.Objective: The aim of this study was to evaluate whether a new immunohistochemical scoring method would be more effective in classifying NETs by reducing staining heterogeneity.Methods: 87 patients with GEP-NET were retrospectively analyzed. Along with the traditional Ki-67 rating, a new score based on the intensity of staining (semiquant Ki-67) was developed. The classification difference between the two methods was determined.Results: The classification of the classification changed significantly when the Ki-67 semi-quant index was used. The percentage of G1 patients increased from 18.4% to 60.9%, while the G2 patients decreased from 66.7% to 29.9% and the G3 patients also decreased from 14.9% to 9.2% %.Conclusions: The new analysis allowed to re-quantify the positive percentages of Ki-67, which can be used both as a marker of proliferation but also as a tool to map tumor dynamics that can influence the diagnosis and guide the choice of therapy.