p53 protein in low-grade astrocytomas: a study with long-term follow-up

Iuzzolino, P.; Ghimenton, Claudio; Nicolato, A.; Giorgiutti, Fabrizia; Fina, Paolo; Doglioni, Claudio; Barbareschi, Mattia

doi:10.1038/bjc.1994.107

Cited by 38 publications

(15 citation statements)

References 37 publications

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“…The fact that multivariate analyses indicated an approximate nine-fold advantage with respect to grade per se helps place these statistical arguments into a clinical frame of reference (Table 3). Increased p53 immunoreactivity resulted in decreased survival with advancing age in a number of prior studies (Iuzzolino et al, 1994;Soini et al, 1994;Pollack et al, 2002). Of note, perhaps the larger of these indicated, much like the trend in our own data, that increased p53 immunoreactivity correlated with a worse prognosis in older children (Pollack et al, 2002).…”

Section: Discussionsupporting

confidence: 79%

“…A number of studies, besides our own, indicate inverse correlations among increased p53 expression and conventional factors indicating a favourable clinical course in astrocytomas (Chozick et al, 1994a;Iuzzolino et al, 1994;Korkolopoulou et al, 1998). Increased p53 protein was detected in a subset of low-grade vs high-grade astrocytomas (Chozick et al, 1994a).…”

Section: Discussionmentioning

confidence: 51%

“…Increased p53 protein was detected in a subset of low-grade vs high-grade astrocytomas (Chozick et al, 1994a). Increased p53 expression occurred in the recurrent vs the initial tumour pairs from the same patient, while tumours recurring within the same histologic grade category, failed to reveal this increase (Chozick et al, 1994a;Iuzzolino et al, 1994;Korkolopoulou et al, 1998;Sarkar et al, 2002). We excluded tumours of oligodendroglial or oligoastrocytic lineage from our analyses, because of the altered natural history as compared to 'pure' astrocytomas, thus increasing the likelihood of genetic mechanisms distinct from those of pure astrocytomas (Burger et al, 1987;Shaw et al, 1992).…”

Section: Discussionmentioning

confidence: 98%

“…Early studies suggested that p53 abnormalities contribute to the development of malignant transformation in astrocytic brain tumours (Frankel et al, 1992;Sidransky et al, 1992). Loss of heterozygosity on human chromosome 17p, 53 point mutations, and altered p53 expression were reported in astrocytomas (Scheffner et al, 1990;Werness et al, 1990;Fujimaki et al, 1991;Lowe and Ruley, 1993;Chozick et al, 1994a;Iuzzolino et al, 1994;Slebos et al, 1994;Morita et al, 1996;Sarkar et al, 2002). Our goal is to assess the significance of potential alterations in p53 protein expression, and its interrelationship with more traditional prognostic factors in astrocytoma tumour progression, in rigorous fashion.…”

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confidence: 99%

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Mutant, wild type, or overall p53 expression: freedom from clinical progression in tumours of astrocytic lineage

Pardo

Hsu

Zeheb³

et al. 2004

Br J Cancer

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Abnormalities of the p53 tumor-suppressor gene are found in a significant proportion of astrocytic brain tumours. We studied tumour specimens from 74 patients evaluated over 20 years at the Massachusetts General Hospital, where clinical outcome could be determined and sufficient pathologic material was available for immunostaining. p53 expression studies employed an affinity-purified p53 monoclonal antibody, whose specificity was verified in absorption studies and, in a minority of cases, a second antibody recognising a different epitope of p53. Significant overexpression of p53 protein was found in 48% of the 74 tumours included in this series and high levels of expression were associated with higher mortality from astrocytic tumours (Po0.001, log rank). Multivariate analyses revealed that immunohistochemically detected p53 was an independent marker of shortened progression-free and overall actuarial survival in patients with astrocytic tumours, suggesting that increased expression of p53 plays an important role in the pathobiology of these tumours. In a subset of 36 cases, coding regions of the p53 gene were completely sequenced via SSCP and direct DNA sequencing, revealing that overexpression of p53 protein is not always associated with point mutations in conserved exons of the p53 gene. Finally, we confirmed p53 protein expression in early-passage human glioma cell lines of known p53 mutational status and immunostaining scores. Although grade continues to be the strongest prognostic variable, the use of p53 staining as a prognostic indicator, in contrast to mutational DNA analyses, may be a useful adjunct in identifying patients at higher risk of treatment failure.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Mutant, wild type, or overall p53 expression: freedom from clinical progression in tumours of astrocytic lineage

Pardo

Hsu

Zeheb³

et al. 2004

Br J Cancer

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“…2,31 Several workers have used proliferation index and p53 gene alterations for prediction of recurrence but results are controversial. 5,8,9,13,15,17,19,24,25,29 Similarly, the relationship between malignant progression and apoptosis is not clearly defined. 3,5,7,24,27 Nakamura et al 24 studied p53 protein expression, MIB-1 labeling index (MIB-1 LI) and apoptotic index (AI) in 46 recurrent anaplastic astrocytomas and reported that MIB-1 LI and AI were higher in the recurrent compared to the initial tumor.…”

Section: Introductionmentioning

confidence: 99%