Prognostication of astrocytoma patient survival by Ki‐67 (MIB‐1), PCNA, and S‐phase fraction using archival paraffin‐embedded samples

Abstract

The prognostic power of three proliferation estimation methods, Ki-67 (MIB-1) and PCNA immunohistochemistry, and flow cytometry (S-phase and S + G2/M fractions, respectively), were evaluated in 50 cases of astrocytoma. Each proliferation index showed a strong association with the grade of malignancy (grades I-IV). The MIB-1 labelling index (LI) provided additional information, as it could be used for the discrimination of grade II and grade III astrocytomas (P = 0.0357). All three proliferation estimation methods also had strong prognostic potential (MIB-1 LI: P < 0.0001; PCNA Li: P < 0.0001; S-phase: P = 0.0004; S + G2/M: P = 0.0124). According to the receiver operating characteristics (ROC) curve, the MIB-1 LI showed generally the best sensitivity and specificity in placing the patients correctly into groups of survivors and non-survivors, which was further confirmed in the multivariate analysis. Only 4 per cent of the patients having high MIB-1 scores (> 15.3 per cent) were alive after 2-years' follow-up. In contrast, 72 per cent of patients with tumours of low proliferation activity survived. It appears that Ki-67 (MIB-1) immunolabelling using archival paraffin-embedded samples is of value in predicting prognosis in astrocytic tumours.

MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor

“…However, other authors have failed to substantiate the prognostic effect of proliferation indices in gliomas (Zuber et al, 1988;Nicoll et al, 1991;Figge et al, 1992;Karkavelas et al, 1995). The rather strong relationship between the three proliferationassociated indices we have used is also in agreement with previously reported findings (Korkolopoulou et al, 1993;Sallinen et al, 1994).…”

“…This is in agreement with the findings of previous studies (Korkolopoulou et al, 1994;Vigliani et al, 1994). The failure of other authors to establish an independent prognostic significance for PCNA LI may be because of different staining protocols and scoring methods (Theunissen and Blaauw, 1993;Sallinen et al, 1994). On the contrary, p53 LI and MDM2 LI were the most statistically significant parameters in predicting disease-free survival independently.…”

“…Various studies performed in this and other laboratories have shown an overall positive correlation between histological grade of gliomas and cellular proliferation parameters, including Ki-67 (or MIB-1) LI (Burger et al, 1986;Zuber et al, 1988;Schroder, 1991;Karamitopoulou et al, 1994;Sallinen et al, 1994), PCNA LI (Allegranza et al, 1991;Louis et al, 1991;Karamitopoulou et al, 1993;Korkolopoulou et al, 1993) and AgNOR number (Maier et al, 1990;Plate et al, 1991;Korkolopoulou et al 1993), lending support to the findings of the present study. However, there is significant overlap in the expression of proliferation indices among various grades, so that none of them can be used as a reliable grading tool.…”

“…The present study strengthens this finding, as well as the prognostic significance of the other indices of cell proliferation (i.e. Ki-67 LI and AgNOR score) (Kajiwara et al, 1990;Sallinen et al, 1994). However, other authors have failed to substantiate the prognostic effect of proliferation indices in gliomas (Zuber et al, 1988;Nicoll et al, 1991;Figge et al, 1992;Karkavelas et al, 1995).…”

Proliferation and aneusomy predict survival of young patients with astrocytoma grade II

“…Proliferation and cytogenetic markers may therefore identify rapid progressive A II. Increased proliferation activity correlates with shorter survival in most series of astrocytomas, although the number of A II was often too small for separate analyses (Sallinen et al, 1994;Korkolopoulou et al, 1997). Numerical chromosomal aberrations have been reported in astrocytomas, such as aneusomy 1, trisomy 7 and monosomy 10.…”