Proliferative activity in human glioblastomas assessed by various techniques

Abstract

Determination of proliferative activity in tumours may be valuable in diagnosis and prognosis. In this study, commonly used proliferation markers were investigated and compared in 12 cases of human glioblastoma. Paraffin sections were incubated with four commercial Ki67-equivalent antibodies, anti-PCNA, and anti-bcl-2. S-phase fraction and mitotic activity were determined as well. The different Ki67 antibodies gave satisfactory immunostainings, though they provided a wide range of proliferation indices (PI) intra- and intertumorally. Correlations between the Ki67 antibodies and the other proliferation markers were, broadly speaking, poor. PCNA immunostaining was hampered by disturbing background staining. Few bcl-2-immunoreactive cells were observed, mainly gemistocytes. Flow cytometric analyses provided reliable S-phase fraction values, and two aneuploid tumours were detected. The mitotic activity was generally high. Thus, mitotic counting remains a convenient method for assessing proliferative activity in astrocytic tumours. Ki67 antibodies are important alternatives, for instance in stereotactic brain biopsies. Under all circumstances, proliferation markers should be used in combination with established histopathological criteria for malignancy in these tumours.

The Accuracy of Survival Time Prediction for Patients with Glioma Is Improved by Measuring Mitotic Spindle Checkpoint Gene Expression

“…We also measuredKi-67 RNA levels because the corresponding protein is currently used to determine a labeling index for glioma [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16] and previous work indicated the RNA might be a better prognosticator [17]. Interestingly, Ki-67 RNA level was outperformed by BUB1B and CDC20, overall, and by BUB1 and TTK when applied to grade II gliomas ( Table 3 ).…”

“…In a widely used measure, the level of Ki-67 protein is determined using an antibody called MIB-1 in a labeling index (MIB Li) that correlates with aggression and survival time in gliomas [6], [7], [8], [9], [10] and many other cancers [11], [12], [13], [14], [15], [16]. Furthermore, one report indicated that RNA expression of Ki-67 correlated with survival time better than the antibody test, MIB Li, in colorectal carcinoma [17].…”

Proliferation Inhibition, DNA Damage, and Cell-Cycle Arrest of Human Astrocytoma Cells after Acrylamide Exposure

“…ACR-induced cell-growth suppression had been reported in many cell types (10,23,24,36,37); but the results for astrocytic cell have not been consistent (14)(15)(16)(17). As compared with proliferating cell nuclear antigen (PCNA), Ki-67 has been recognized as a more specific indicator for the proliferative activity of human glioblastomas (38)(39)(40). Thus, results from the MTT assays and Ki-67 expression using longer exposure times (>24 h) in the current study provide a better correlation between ACR treatments and proliferation inhibition.…”

Determination of proliferation index in neoplasms using different Ki‐67 equivalent antibodies

“…The other studies have revealed divergent findings that may more or less be explained by counting random areas of heterogeneous tumours. Thus, the differences in LIs between two readings or between counts from various areas were found to be greater than those between each of the antibodies (10,11). Studying quantitative differences between Ki-67 equivalent antibodies therefore necessitates that all counts are performed in exactly the same tissue areas.…”

“…We have previously determined Ki‐67 LIs in various intracranial neoplasms applying the same four antibodies as were used in our two methodologically standardized studies (10–13). In meningiomas (12) we found an antibody ranking identical to that of our former study (9), although the difference between MIB‐1 and NCL‐Ki‐67p was negligible.…”