Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients

Kucera, E; Speiser, Paul; Gnant, Michael; Szabo, Ladislaus; Samonigg, Hellmut; Hausmaninger, H.; Mittlböck, Martina; Fridrik, Michael A.; Seifert, Michael; Kubista, E.; Reiner, Agnes T.; Zeillinger, Robert; Jakesz, R.

doi:10.1016/s0959-8049(98)00400-6

Cited by 31 publications

(14 citation statements)

References 22 publications

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“…33 However, in a series of node-positive and steroid receptor-positive breast cancer patients, p53 mutation predicted a worse prognosis, but specific mutations in the L2/L3 domains were not an independent indicator for prognosis (n=42). 45 Bergh et al performed complete sequencing of the p53 gene in a series of 316 breast cancer patients, 24 but their data on the relationship between specific mutations and patient survival are not compatible with those reported by Børresen et al It is difficult to explain these different reported observations, but an evident problem with these types of studies is that in breast cancer the proportion of tumours with a p53 mutation is relatively The mean apoptotic index was calculated as described in Table III. *Kruskal-Wallis one-way analysis of variance.…”

Section: Discussionmentioning

confidence: 99%

“…An additional problem is that up to 20 per cent of p53 mutations have been reported to occur outside exons 5-8. As a result, when only exons 5-8 are screened, [31][32][33]45 a small number of patients with a p53 mutation located outside exons 5-8 will be missed. For this reason, the reported correlations between specific p53 mutations and survival of breast cancer patients have to be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

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Mutations in exons 5-8 of thep53 gene, independent of their type and location, are associated with increased apoptosis and mitosis in invasive breast carcinoma

et al. 1999

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In breast cancer, mutations located in the zinc‐binding functional domains of the p53 gene have been reported to predict a worse prognosis and a worse response to treatment with doxorubicin, compared with mutations in other parts within exons 5–8 of the gene. Similarly, mutations in residues of p53 that directly contact DNA have been associated with a poor prognosis. To investigate whether these specific p53 mutations are associated with differences in the rate of apoptosis and/or mitosis, or expression of the anti‐apoptotic Bcl‐2 protein, these parameters were evaluated in 89 invasive breast cancers with a confirmed p53 mutation in exons 5–8 and in 99 tumours without a p53 mutation in exons 5–8. Neither mutations located in the zinc‐binding functional domains nor mutations in residues that directly contact DNA were associated with alterations in mitotic or apoptotic activity. However, compared with the wild‐type p53 tumours, both apoptotic and mitotic indices showed an approximately two‐fold increase in the mutant p53 group ( p< 0·001). The presence of a p53 mutation was also associated with the presence of tumour necrosis ( p< 0·001), high tumour grade ( p< 0·001) and low expression of Bcl‐2 ( p< 0·001). Our data support the concept that in invasive breast carcinoma, loss of p53 function is involved in enhanced proliferation rather than decreased apoptosis and that the resulting acceleration of cell turnover may enhance clonal evolution and tumour progression. Copyright © 1999 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutations in exons 5-8 of thep53 gene, independent of their type and location, are associated with increased apoptosis and mitosis in invasive breast carcinoma

et al. 1999

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“…Several studies have revealed that specific p53 mutations are associated with either a poorer prognosis or a poor response to treatment (TABLE 1). In breast [37][38][39] and colon cancer 40,41 , there is a strong association between mutations in the L2/L3 loop and shorter survival or poor response to treatment. These data are also NATURE REVIEWS | CANCER VOLUME 1 | DECEMBER 2001 | 2 3 5 …”

Section: The P53 Family Members P63 and P73mentioning

confidence: 99%

Assessing TP53 status in human tumours to evaluate clinical outcome

2001

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TP53 is probably the most extensively studied tumour-suppressor gene, and patients with TP53 mutations are known to have a poor outcome. However, inconsistencies in the analysis of TP53 status, and failure to realize that different mutations behave in different ways, prevent us from effectively applying our vast knowledge of this protein in clinical practice. What simple steps can be taken to ensure that patients benefit from our understanding of TP53?

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“…Several studies have revealed that specific TP53 mutations are associated with either a poorer prognosis or a poor response to treatment. In breast [Berns et al, 1998;Borresen et al, 1995;Kucera et al, 1999] and colon cancer [Borresen Dale et al, 1998;Goh et al, 1995], there is a strong association between mutations in the L2/ L3 loop and shorter survival or poor response to treatment. These data are also emphasized by the observation that the distribution of tumors in Trp53 -/-(Trp53 is the mouse gene encoding TP53) mice differs from that of mice harboring point mutations [Liu et al, 2004;Olive et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

The UMD TP53 database and website: update and revisions

et al. 2006

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Mutation of the p53 gene is the most frequent genetic alteration found in human cancer, but it is also the most frequently reported with more than 22,000 mutations published in 2,000 papers. In 1991, we developed a database and software to handle and analyze all this information. The database has been widely used for clinical analysis and molecular epidemiology. We have expanded the scope of the database by integrating structural, phylogenetic and biological information on wild-type (wt) and mutant TP53. Integration of the TP53 mutant activity database provides unique information that will be useful to both clinicians and scientists. All of this information is available from a new website (www.umd.be:2072/) that will generate a detailed informative page for every TP53 mutant in the database. New tools to check TP53 mutations and minimize errors found in the literature are also available.

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Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients

Cited by 31 publications

References 22 publications

Mutations in exons 5-8 of thep53 gene, independent of their type and location, are associated with increased apoptosis and mitosis in invasive breast carcinoma

Mutations in exons 5-8 of thep53 gene, independent of their type and location, are associated with increased apoptosis and mitosis in invasive breast carcinoma

Assessing TP53 status in human tumours to evaluate clinical outcome

The UMD TP53 database and website: update and revisions

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