Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours

Jaros, Evelyn; Perry, Robert H.; Adam, Liana; Kelly, Peter; Pj, Crawford; Kalbag, R. M.; Mendelow, A. D.; Sengupta, Ranjan; Pearson, Andrew D.J.

doi:10.1038/bjc.1992.273

Cited by 241 publications

(135 citation statements)

References 45 publications

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“…A plausible explanation is that increased MDM2 expression inactivates p53, blocking its antiproliferative function. There is a limited number of studies addressing the possible association of p53 immunopositivity with poor prognosis (Jaros et al, 1992;Soini et al, 1994), the findings of which agree with ours, although unpublished data reported by Louis et al (1994) have failed to confirm this association. Taking into account that p53 mutations are commoner in younger patients and in astrocytomas progressing stepwise to glioblastomas (van Meyel et al, 1994), it is tempting to hypothesize that patients whose tumours carry p53 mutations may survive longer.…”

Section: Discussionsupporting

confidence: 85%

“…The association between p53 LI and EGFR LI, as well as the simultaneous expression of these two molecules in a significant proportion (23%) of our cases, suggests that p53 and EGFR may be involved in early stages of glial tumorigenesis, as hypothesized by Jaros et al (1992) and Rasheed et al (1994), and that this expression may be associated with progression to more anaplastic forms of gliomas. The cytoplasmic distribution of EGFR that we and others (Jaros et al, 1992) have observed may be explained by rapid internalization of the EGF-EGFR complex or by cytoplasmic binding of EGFR to TGFa (Jaros et al, 1992). In univariate analysis, EGFR expression failed to emerge as a significant predictor of survival, in contrast to the findings of Diedrich et al (1995) and Zhu et al (1996).…”

Section: Discussioncontrasting

confidence: 70%

“…age, PCNA LI, Ki-67 LI and AgNOR score were categorized on the basis of the mean value; Ki-67 was also considered in the form of < 5% vs . 5% according to the results of a previous study (Jaros et al, 1992 p53 and MDM2 labelling were restricted to tumour cell nuclei. Oligodendrogliomas were negative for p53, and pilocytic (grade I) astrocytomas were negative for both p53 and MDM2.…”

Section: Discussionmentioning

confidence: 67%

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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: 85%

Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 67%

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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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“…Montine et al 21 reported that a MIB-LI >7.5% was associated with higher histological grade and poorer survival. Jaros et al 14 found a LI of >5% to be the threshold value for predictive shorter survival. McKeever et al 20 in their analysis of 50 cases of grade II astrocytomas, used an LI of 2% as cut off value and found that 82% of patients who had a MIB-1 LI of > 2% died within the 10 year follow up period while only 23% of patients who had a MIB-1 LI of ≤2% died within the same period.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors

Ralte

Sharma

Karak

et al. 2001

Pathol. Oncol. Res.

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“…Paraffin-embedded sections (4 gm) were incubated with the DO-7 monoclonal antibody (DO-7; Novocastra) to the TP53 protein at a 1:250 dilution using standard immunohistochemical staining methods, as described previously (Jaros et al, 1992). Sections of colorectal carcinoma previously found to show intense nuclear staining for DO-7 were used as positive controls.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Alterations of TP53 in microdissected transitional cell carcinoma of the human urinary bladder: high frequency of TP53 accumulation in the absence of detected mutations is associated with poor prognosis

Abdel-Fattah

Challen²,

Griffiths³

et al. 1998

Br J Cancer

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NE2 4HH; 3Department of Pathology, Freeman Hospital, Freeman Rd, Newcastle upon Tyne NE7 7DN, UK Summary We have used microdissection of paraffin-embedded histological sections and polymerase chain reaction (PCR)-based direct DNA sequencing for 54 transitional cell carcinoma (TCC) of the bladder, to examine critically the association between TP53 nuclear accumulation determined by immunohistochemistry and the presence of TP53 mutations, and to examine their relationship to tumour stage and grade, as well as patient survival. There was a significant association between the presence of TP53-positive nuclei (> 10%) and a higher histological stage and grade (P = 0.0115, P = 0.0151 respectively; Fisher's exact). A significant association between TP53 gene mutations and TP53 nuclear reactivity in more than 10% of tumour cell nuclei was also observed (P = 0.0003; Fisher's exact). Mutations were detected in 18/54 (33%) cases together with the wild-type sequence when analysed from bulk frozen samples, with significant clustering of mutations in exons 7 and 8. The microdissection method distinguished more clearly between heterozygous and/or homozygous alterations of the TP53 tumour-suppressor gene, and clearly showed frequent accumulation of TP53 in the absence of mutations. When microdissecting immunonegative regions from the same paraffin sections, three out of ten samples showed the identical mutations detected in the immunopositive regions. There was a significant association between TP53 immunoreactivity in more than 50% of tumour cell nuclei and decreased survival among all patients (P = 0.0325; log-rank test). The patients with TP53 mutations showed a trend for a shorter survival period; however, the association was not statistically significant at the 95% confidence level (P = 0.132; log-rank test). In conclusion, our observations show that accumulation of TP53 occurs frequently in the absence of mutations, and that such accumulation is nevertheless associated with poor survival when it occurs in a high proportion (> 50%) of tumour cell nuclei.Keywords: TP53; mutation; immunohistochemistry; bladder cancer; microdissection Ten thousand individuals per year in England and Wales develop bladder cancer and 5800 die as a result of the disease (Office of Population Census Statistics, 1993). A total of 90% of bladder tumours are transitional cell carcinoma (TCC), whereas less common histological types include squamous cell carcinoma, adenocarcinoma and sarcoma. Molecular genetic and immunopathological analyses of bladder cancer have identified abnormalities in a number of chromosomes and genes that appear to be implicated in the development and progression of such tumours. These include activation of the H-RAS oncogene (Fujita et al, 1987;Burchill et al, 1994;Hong et al, 1996;Vageli et al, 1996), increased expression of epidermal growth factor receptor (Neal et al, 1990) and inactivation of the retinoblastoma gene (Lipponen and Liukkonen, 1995) as well as frequent abnormalities of the TP53 tumour-suppressor gene.TP53 is ...

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Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours

Cited by 241 publications

References 45 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

Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors

Alterations of TP53 in microdissected transitional cell carcinoma of the human urinary bladder: high frequency of TP53 accumulation in the absence of detected mutations is associated with poor prognosis

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