Is Ki-67 index overexpression in IDH wild type glioblastoma a predictor of shorter Progression Free survival? A clinical and molecular analytic investigation

Background: Ki-67 proliferation index is widely used for differentiating between high and low-grade gliomas, but differentiating between the same grade IV appears to be more problematic, and the point about its prognostic value for GBM patients remains unclear. To reduce the possibility to find a marked histological heterogeneity, and may contain areas that could be diagnosed as lower grade, in this study we considered a large group of patients with IDH wild-type Glioblastoma (IDH-WT GBM) and we have analyzed previously reported prognostic factors, in regards to their relationship with the Ki-67 expression index. Methods: We explore the prognostic impact of ki-67 index status in 127 patients affected by IDH-WT GBM. We therefore analyzed clinical characteristics, tumor genetics, dimension and clinical outcomes. We selected a total of 127 patients affected by newly diagnosed IDH-WT GBM who underwent surgery, radiation, and chemotherapy in our Institution in the period ranging between January 2014 and December 2016 RESULTS: The volume of the lesion had a strong association with the Ki67 overexpression. In particular lesions whose volume was greater than 45 cm3, presented a higher percentage of Ki67 expression demonstrating that greater tumors are more likely associated to higher values of Ki67 percentages. On a multivariate analysis, it was possible to outline that Ki67 was significant a predictor of shorter PFS independently from the age of the patients, the volume of the lesion and preoperative KPS. Conclusions: There is a correlation between percentage staining of Ki-67 and OS in our cohort of patients with IDH-WT GBM. This is only the third observational study documenting a positive correlation between Ki-67 and overall survival in GBM and the first one demonstrates that percentage Ki-67 staining >20 % predicts poorer progression free survival in IDH-WT GBM.