Heterogeneity of Ki-67 and p53 Expression in Glioblastoma

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Introduction. Heterogeneity is a characteristic feature of malignant tumours. It challenges the treatment regimens as well as can impair the diagnostic accuracy. Glioblastoma multiforme (GBM), a high-grade malignant glial tumour, is known for the extreme morphological heterogeneity giving rise also to the term itself.

Aim of the study was to evaluate heterogeneity of pathogenetically and diagnostically important cardinal tumour features, namely, cellular proliferation and tumour suppressor protein expression in GBMs.

Material and methods. The study group comprised 101 GBMs, retrospectively identified by archive search. The inclusion criteria comprised validated diagnosis (by World Health Organisation criteria) and lack of prior treatment. Recurrent GBMs as well as other glial and non-glial tumours were excluded from the study. Insufficient tissue materials comprising stereotactic biopsies and tissues affected by widespread necrosis (exceeding 90%) were also excluded. Proliferation activity (by Ki-67) and expression of aberrant p53 protein was detected by immunohistochemical investigation (IHC) of formalin-fixed, paraplast-embedded tumour samples. Polymeric visualisation system was used to detect bound primary antibodies. The expression of each antigen was measured by computed morphometry in at least 200 cells of hot and cold spots in each tumour. The data were expressed as the relative value. Heterogeneity was estimated as the mathematical difference between the highest and lowest expression value in each tumour. Descriptive statistics was applied. The 95% confidence intervals (CI) were determined as well.

Results. The highest proliferation activity ranged 15 – 95%; mean 43.9% [95% CI = 40.3 – 47.6]. The lowest proliferation activity ranged 2 – 95%, mean 20.1% [16.8 – 23.4]. The mean proliferation heterogeneity was 23.8% [21.5 – 26.2]; range 0 – 67%. The mean heterogeneity of p53 protein expression was 11.7% [8.9 – 14.6], ranging 0 – 75%.

Conclusions. GBM is characterized by marked heterogeneity regarding proliferation rate and expression of p53 protein that may affect diagnostic accuracy and grading of gliomas in small samples of tissue material as well as survival in case of small residual tumour after surgical treatment.


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Acta Chirurgica Latviensis

The Journal of Riga Stradins University; Latvian Association of Surgeons; Latvian Association of Paediatric Surgeons

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