Accuracy of visual assessments of proliferation indices in gastroenteropancreatic neuroendocrine tumours

Abstract

Manual tally counts of 2000 cells exhibited similar levels of accuracy to the gold standard, especially at low PIs. Eyeball estimates were significantly less accurate than the gold standard. This suggests that tumour grades may be misclassified by eyeballing and that formal tally counting of positive cells produces more reliable results. Further studies are needed to identify accurate clinically appropriate ways of calculating.

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

“…However, multi-institutional studies showed that formal counting was more reproducible than estimation in breast cancer [53,75]. Similar observation were made in NEN: results of eyeballed estimation differed from results of counting [20,21,25] and were irreproducible [25], but some investigators showed that estimation was not as bad [27,28]. Pathologists in general overestimate the Ki67 LI during eye-balled estimation in comparison to counting technique [25,27].…”

“…Analytical validity is a sine qua non condition for any tumour biomarker which is intended to be used in clinical practice and to influence management of the patients [18]. Selected aspects of analytical validity of Ki67 LI in NEN were previously studied [19,20,21,22,23,24,25,26,27,28].…”

Neuroendocrine Tumors of the Luminal Gastrointestinal Tract

“…The mitotic index should be calculated by counting at least 500 and preferably 2000 cells; studies have noted that ''eyeballing'' and estimating the percentage is quite inaccurate, particularly at lower levels of activity, and therefore a strict count (either manual or by image analysis methods) is recommended. 47,48 There is general agreement that the count should be performed in the area of highest mitotic activity (hotspots). However, concern remains about what level of staining constitutes a true positive nuclear staining; Young et al 48 noted specifically that ''cells were considered positive if they showed any evidence of taking up stain.''…”

“…47,48 There is general agreement that the count should be performed in the area of highest mitotic activity (hotspots). However, concern remains about what level of staining constitutes a true positive nuclear staining; Young et al 48 noted specifically that ''cells were considered positive if they showed any evidence of taking up stain.'' While this appears logical, validation of this approach is not available.…”

Improving reliability of live/dead cell counting through automated image mosaicing

“…Nevertheless, two operators only were enrolled to count, and they did not even analyzed live and dead cells separately. Recently, Young et al [44] improved the statistics by asking four operators to count, but they did not report results regarding either inter-observer variability or dead cells. In conclusion, no statistical analyses have been reported in literature to extensively compare the gold standard method with an approach based on a labelled mosaic.…”