Evaluation of the proliferation marker Ki-67 in gliomas: Interobserver variability and digital quantification

Abstract

BackgroundThe Ki-67 Labelling Index (LI) is used as an ancillary tool in glioma diagnostics. Interobserver variability has been reported and no precise guidelines are available. Nor is it known whether novel digital approaches would be an advantage. Our aim was to evaluate the inter- and intraobserver variability of the Ki-67 LI between two pathologists and between pathologists and digital quantification both in whole tumour slides and in hot spots using narrow but diagnostically relevant intervals.MethodsIn samples of 235 low and high grade gliomas, two pathologists (A and B) estimated the Ki-67 LI (5–10% intervals) for whole tumour slides and for hot spots. In 20 of the cases intraobserver variability was evaluated. For digital quantification (C) slides were scanned with subsequent systematic random sampling of viable tumour areas. A software classifier trained to identify positive and negative nuclei calculated the Ki-67 LI. The interobserver agreements were evaluated using kappa (κ) statistics.ResultsThe observed proportions of agreement and κ values for Ki-67 LI for whole tumour slides were: A/B: 46% (κ = 0.32); A/C: 37% (κ = 0.26); B/C: 37% (κ = 0.26). For hot spots equivalent values were: A/B: 14% (κ = 0.04); A/C: 18% (κ = 0.09); B/C: 31% (κ = 0.21).ConclusionsInterobserver variability was pronounced between pathologists and for pathologists versus digital quantification when attempting to estimate a precise value of the Ki-67 LI. Ki-67 LI should therefore be used with caution and should not be over interpreted in the grading of gliomas. Digital quantification of Ki-67 LI in gliomas was feasible, but intra- and interlaboratory robustness need to be determined.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0711-2) contains supplementary material, which is available to authorized users.

TRIM31 promotes proliferation, invasion and migration of glioma cells through Akt signaling pathway

“…Besides, immunohistochemistry of TRIM31 expression in 80 glioma samples further confirmed that TRIM31 was overexpressed in high grade gliomas ( Figure 1B), since immunohistochemistry can be used to localize, characterize and quantify antigens in tissues and cells [17]. From the Spearman rank test result in Figure 1C, it's obvious that there was a positive relationship between TRIM31 and Ki-67 expression (r=0.779, p<0.001), and Ki-67 is widely used as an ancillary tool for the diagnosis and prognosis of glioma [18]. The clinicopathological features of the 80 samples were presented in Table 1, which included 25 cases of Grade II gliomas, 31 cases of Grade III gliomas and 24 cases of Grade IV gliomas.…”

Correlation Between Digital and Manual Determinations of Ki-67/MIB-1 Proliferative Indices in Human Meningiomas

“…Thus, data are scarce regarding digital determinations of MIB-1 PIs in human meningiomas. However, similar studies have been performed in other tumors, such as breast cancer, 19 gliomas, 20 gastrointestinal stromal tumors, 21 and prostate cancer. 22 In those studies, a generally good correlation was established between manual and digital determinations of MIB-1 PIs, but the prognostic aspects varied.…”

Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo

“…Ki‐67 was present in all active phases of cell cycle, but absent from resting cells . The prognostic value of Ki‐67 for survival and tumor recurrence have been confirmed in some cancer types, such as breast cancer, prostate cancer and neuroendocrine cancer . It also shows prognostic potential in ESCC .…”