The implications of the heterogeneous distribution of Ki-67 labelled cells in meningiomas

Ki-67 monoclonal antibody reacts with a nuclear protein only expressed in proliferating cells. In order to evaluate the applicability of Ki-67 in meningiomas we determined the index of labelled cells in 52 biopsies. Two counting methods were used to calculate the labelling index. The mean Ki-67 index was determined by the number of positive Ki-67 cells in three randomly chosen fields divided by the total number of cells in the three fields. The preparations were also screened for the area with the highest percentage of positive Ki-67 cells, yielding the 'highest' Ki-index. The three patients who developed a recurrence did not show an elevated Ki-67 index by any of the two counting methods. Because of the differences observed between the two counting methods and the differences of the Ki-67 indices in the three randomly chosen fields we performed a statistical analysis to evaluate the possibility of a heterogeneous distribution of Ki-67 positive cells in meningiomas. Homogeneity was rejected if the data showed no Poisson distribution. We found that five of the 13 tumours which had a mean Ki-67 index greater than 1.00% were heterogeneous (38.4%). One of the highest differences between the two counting methods (5.05%) was noted in the only tumour with local signs of malignancy. Our results indicate a heterogeneity of the labelling of Ki-67 in histologically benign meningiomas and emphasise the importance of representative sampling. More attention should be paid to this heterogeneity for cell kinetic studies in brain tumours, and one should be aware that regrowth is not only determined by the proliferative capacity.