Correlation of histology, cytogenetics and proliferation fraction (Ki-67 and PCNA) quantitated by image analysis in...

Sixty meningiomas were classified histologically according to the WHO criteria and analyzed cytogenetically. The Ki-67 and PCNA proliferation fractions (PRFs) were assessed by immunhistochemistry. The staining results were quantified by TV-image analysis (Miamed, Leica, Germany). Within meningiomas of WHO-grade II/III and those with complete or partial deletion of # 1p, we found a significantly higher mean and maximal Ki-67 PRFs than in those of WHO-grade I and those with all other karyotypes. This was not the case for PCNA PRFs. No differences in PRFs were detectable between histological subtypes. Although these results were obtained after measurement of five high power fields (HPFs) only, the heterogeneity of PRF distribution within the tumors was high. Even after the measurement of 100 HPFs, the 95% confidence intervals were in a range of 18% to 34.3% PRF. This finding seems to be responsible for the moderate interobserver reproducibility of image analytical determination of PRF (r = 0.74). Nevertheless, there was a good correlation between subjective and objective image analytical assessment of PRF (r = 0.83). The significance of the maximum Ki-67 PRF per specimen implies the possibility of selecting those areas which show the highest fraction of positively stained nuclei for measurement, avoiding the problem of intraslide heterogeneity. Thus the time needed for image analytical quantification may be reduced.