Prognostic significance of proliferating cell nuclear antigen (PCNA) expression in gliomas

Korkolopoulou, P.; Christodoulou, Panayiotis; Lekka-Katsouli, I.; Kouzelis, Konstantinos; Papanikolaou, Angelos; Panayotides, I.; Mariatos, P; Thomas-Tsagli, Euphemia; Crocker, J

doi:10.1111/j.1365-2559.1994.tb01353.x

Cited by 22 publications

(16 citation statements)

References 34 publications

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“…The information conveyed by these parameters is superior to that yielded by conventional histopathological grading. 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).…”

Section: Discussionsupporting

confidence: 92%

“…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. In a previous study (Korkolopoulou et al, 1994), we found that PCNA LI has a significant impact on glioma survival. The present study strengthens this finding, as well as the prognostic significance of the other indices of cell proliferation (i.e.…”

Section: Discussionmentioning

confidence: 64%

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

Korkolopoulou

Christodoulou²,

Kouzelis³

et al. 1997

Br J Cancer

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Summary p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in paraffin-embedded tissue from 61 patients with central nervous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We used the monoclonal antibodies PC-1 0, MIB-1, DO-1, 1 Bi 0 and EGFR 113 and the colloid silver nitrate (AgNOR) technique. MDM2 and p53were co-expressed in 28% of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53-negative/MDM2-positive phenotype in 20% of cases. There was a positive correlation of p53 and MDM2 expression with grade and proliferation indices. Univariate analysis in the group of diffuse astrocytomas showed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR score, tumour location and grade influenced diseasefree survival (P < 0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age, radiotherapy, PCNA LI and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were independent predictors of disease-free survival, and grade was the only independent predictor of post-relapse survival. Our results indicate that p53 LI and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67) are useful indicators of overall and disease-free survival in diffuse astrocytoma patients.Keywords: proliferating cell nuclear antigen; Ki-67; MIB-1; AgNORs; p53; MDM2; epidermal growth factor receptor; gliomas Central nervous system (CNS) gliomas range in clinical behaviour and histological appearance from indolent well-differentiated lesions to highly anaplastic, rapidly growing neoplasms. A cardinal property of almost all types of gliomas is a propensity to recur and undergo anaplastic change (Russel and Rubinstein, 1989). A major stimulus to the study of cell proliferation in gliomas has been the widely held belief that quantification of this fundamental process will be of value in the objective categorization of these tumours. However, while cell kinetic information is an important aspect of the biology of gliomas, it has become clear that neoplastic evolution towards glioblastoma is a multistep process that involves deregulation of several genes related to both cellular proliferation and differentiation. The molecular determinants of glioma progression are still under investigation, with considerable attention directed towards the tumour-suppressor gene p53. On the basis of findings from molecular genetic analysis, Bigner and Vogelstein (1990)

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 64%

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

Korkolopoulou

Christodoulou²,

Kouzelis³

et al. 1997

Br J Cancer

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“…This relation has been seen in other series with large number of cases snd utilising other proliferation markers as well [7,16,20,22,23]. The range of PCNA LI is variable, from 0.00-30.96% in some studies [20,23] to 0.1-95% in others [7,16,22].…”

mentioning

confidence: 71%

“…However, difference in survival between low PCNA LI group (25.18 months) and high PCNA LI group (9.15 months) was not significant. While a few studies say PCNA loses significance when compared in multivariate analyses to age, grade and type [23,25] several studies have shown a significant association with prognosis [16,22].…”

mentioning

confidence: 99%

Astrocytomas and Prognosis-From Morphology to Tumor Biology

Lakhtakia

Trehan²,

Rai

et al. 2000

Medical Journal Armed Forces India

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Twenty-seven cases of Astrocytoma were studied to assess the role of a newly introduced proliferation marker-Proliferating Cell Nuclear Antigen (PCNA) in improving prognostic accuracy in comparison to traditional histologic methods like grading. The study revealed a direct correlation between grading and PCNA expression as determined by labelling indices (LI). A 25% PCNA LI separated low and high grade tumors. The difference between PCNA U's of patients who were alive and those who were dead at the end of the study was statistically significant. However, in this study with limited follow-up, statistically significant relation to survival and recurrence could not be established. The study introduces a new method of assessing tumor biology that enables objectivity in prediction of tumor behaviour.

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“…However, the question of whether its prognostic value simply parallels or actually exceeds the prognostic value of H&E histopathology alone has not been answered as clearly for PCNA as for BUDR. Multivariate analysis of clinicopathological indices and PCNA LIs of 45 gliomas showed that only PCNA and histopathological diagnosis independently predicted survival (Korkolopoulou et al 1994). Other studies have shown PCNA predictive to a limited extent, but not independent of other factors by multivariate analysis (Ang et al 1994;McKeever et al 1997b).…”

Section: Figures 6-9mentioning

confidence: 95%

Insights About Brain Tumors Gained Through Immunohistochemistry and in Situ Hybridization of Nuclear and Phenotypic Markers

McKeever

1998

J Histochem Cytochem.

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Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.

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Prognostic significance of proliferating cell nuclear antigen (PCNA) expression in gliomas

Cited by 22 publications

References 34 publications

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

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

Astrocytomas and Prognosis-From Morphology to Tumor Biology

Insights About Brain Tumors Gained Through Immunohistochemistry and in Situ Hybridization of Nuclear and Phenotypic Markers

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