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Abstract

Although several studies have examined brain tumor markers for prognostic value, few investigations have stratified analysis based on specific histologic grade. The objective of this study was to evaluate a single histologic grade of glioma, the grade IV glioma or glioblastoma (World Health Organization Classification), with a comprehensive panel of tumor markers in an attempt to identify those with prognostic significance. Tumor samples from a cohort of patients with glioblastoma multiforme (n = 32) were examined for tumor markers, DNA analysis, and clinical variables in an attempt to determine a 'profile' for this tumor. We used univariate and multivariate statistical analysis to determine the prognostic value of tumor cell ploidy, percent S-phase, DNA index, p53, and Ki-67 labeling index, as well as the variables of gender, race, age, location of tumor, history of chemotherapy, and primary versus recurrent tumor. Two additional tumor markers, multidrug resistance gene 1 and glutathione-S-transferase subtype pi, were included in the sample testing, but were not analyzed statistically. Univariate analysis indicated that increasing age had a strong association with decreased survival. Female gender, increasing Ki-67, no chemotherapy before sample collection, and primary glioblastoma showed some association with decreased survival in the univariate model. The univariate results indicated that race, side of tumor, ploidy, S-phase, DNA index, and p53 had no prognostic value. Multivariate modeling demonstrated that age, gender, and Ki-67 were the strongest factors associated with survival. The relevant literature is reviewed.

Low expression of Ki-67/MIB-1 labeling index in IDH wild type glioblastoma predicts prolonged survival independently by MGMT methylation status

“…The Ki-67/MIB-1 labeling index (LI) is one of the immunohistochemical markers used for discriminating between high and low-grade gliomas [ 9 ], whilst its use as prognostic factor for the stratification is still discussed [ 10 – 20 ]. Thus, whilst some studies show no association between Ki-67 LI and survival [ 13 , 14 , 21 ], and no predictive value [ 10 , 21 ], others show a poorer survival rate for lower Ki-67 LI [ 14 , 19 ], whilst others the opposite [ 11 , 12 , 15 – 18 , 20 ]. Notably, nowadays, no studies have still been performed on the relationship between Ki-67/MIB-1 labeling index and IDH1-WT status in GBM.…”

Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

“…A common feature, however, is the lack of comparable results for the high and low index groups in-between studies, with different teams using 5%, 10% or 20% margin for a cutoff value. This not only yields all results incomparable, but also contradictory to one another [ 14 , 17 , 21 ].…”

“…However, some of these studies do not state the means of calculating the Ki-67 index [ 11 ]. Other research teams state that the estimation was carried on pathologist interpretation only, excluding a standardized approach to Ki-67 index estimation [ 14 , 17 ]. In some of these studies, a very strong statistical correlation is declared with a very low p-value, whilst at the same time the standard deviations of different groups significantly overlap one another [ 13 , 16 - 17 ].…”

Imaging the life and death of tumors in living subjects: Preclinical PET imaging of proliferation and apoptosis

“…Moreover, tumor cell proliferation has been identified as an important surrogate marker of survival, as determined by staining of ex vivo biopsy specimens with proliferation markers such as Ki67. 43,44 Such ex vivo determinations, which do not apply to non-resectable or disseminated cancers, may fail to predict actual therapy responsiveness because of biopsy sampling errors, intratumoral biological heterogeneity, and non-uniform drug delivery. 45 PET imaging of cell proliferation may address these limitations, providing a serial 3-dimensional assessment of tumor growth or regression in vivo.…”