Prognostic significance of TP53 alterations in breast carcinoma

Andersen, TI; Holm, Ruth; Nesland, Jahn M.; Heimdal, Ketil; Ottestad, Lars; Børresen, Anne Lise

doi:10.1038/bjc.1993.383

Cited by 155 publications

(97 citation statements)

References 40 publications

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“…The proportion of cancers with p53 mutation (20%), p53 allele loss (41%), p53 mRNA expression (54%) and overexpression (28%) or p53 protein expression (32%) are similar to the reported series (Cattoretti et al, 1988;Davidoff, 1991;Iwaya, 1991;Kovach et al, 1991;Osborne et al, 1991;Runnebaum et al, 1991;Varley et al, 1991;Vojtesek et al, 1992;Andersen et al, 1993;Barnes, 1993;Friedrichs, 1993;Martinazzi, 1993;Thorlacius et al, 1993;Tsuda et al, 1993;Marks et al, 1994;Bergh et al, 1995;Borressen et al, 1995;Stenmark-Askmalm et al, 1995).…”

Section: Discussionsupporting

confidence: 74%

“…1, mutation (demonstrated at the DNA level) has been associated with poor prognosis on 3-6 years follow-up (Andersen et al, 1993; Thorlacius et al, 1993;Silvestrini et al, 1996). Furthermore, the precise location of the mutation may add further information of prognostic value (Bergh et al, 1995;Borressen et al, 1995) and predict response to chemotherapy (Elledge et al, 1995;Aas et al, 1996).…”

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confidence: 99%

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Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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Summary Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41 %) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (1 7p1 3.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

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Section: Discussionsupporting

confidence: 74%

mentioning

confidence: 99%

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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“…Mutations in p53 often accompany the progression of solid tumors towards metastasis (Kastrinakis et al, 1995;Marchetti et al, 1993;Andersen et al, 1993;Ulbright et al, 1994). Since p53 was shown to be responsible for apoptosis induced by anticancer treatment, its inactivation in metastatic tumors may partially account for their resistance to therapy (Fugmann et al, 1977;Tsuruo and Fidler, 1981).…”

Section: Discussionmentioning

confidence: 99%

Suppression of apoptosis by bcl-2 does not prevent p53-mediated control of experimental metastasis and anchorage dependence

et al. 1997

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Mutations in the p53 tumor suppressor gene are frequently associated with the metastatic stage of tumor progression. Inactivation of p53 was shown to promote metastasis under experimental conditions. To determine the p53 functions that are involved in the control of tumor metastasis, we compared properties of three types of transformed mouse ®broblasts: with intact p53, with p53-mediated apoptosis suppressed by bcl-2 and with p53 inactivated by dominant negative mutants. Although expression of bcl-2 blocked apoptosis in detached cells and increased tumor cell survival in the blood circulation, it was insu cient to a ect the ability of p53 to cause cell cycle arrest in detached cells and suppress experimental metastasis. For the suppression of metastasis complete inactivation of p53 was required. We conclude that the apoptotic function of p53 is dispensable for the p53-dependent suppression of experimental metastasis that is presumably achieved by controlling anchorage dependence. These data provide a possible explanation to dramatic di erences in values of bcl-2 and mutant p53 as prognostic markers in human cancer.

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“…In contrast, for some cancer types evidence has been obtained that p53 mutations are associated with worsened clinical outcome, e.g. in breast cancer (Andersen et al, 1993) and in colorectal cancer (Hamelin et al, 1994). Furthermore, some speci®c types of mutations located in regions involved in DNA binding have been shown to correlate with resistance to primary and adjuvant therapy and with survival in breast cancer (Bergh et al, 1995;Aas et al, 1996) and colorectal cancer (Goh et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer

et al. 1998

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Recent studies have suggested that di erent mutation types within the core domain of the tumour suppressor protein p53, i.e. DNA contact mutations and structural mutations, confer di erent biological properties. We have analysed in 86 head and neck squamous cell carcinomas (HNSCC), whether these p53 mutation types have a di erential clinical impact. Thirty-seven missense mutations were identi®ed. Thirteen of these (36%) were DNA contact mutations, occurring in the L3 loop, in the H2 loop sheet helix motif, in the S10 b strand and in Zinc binding residues. Microsatellite marker analysis revealed a selective association between these mutations and the loss of wild-type alleles (100% LOH vs 50% LOH in tumours with structural mutations; P=0.0034, Fisher's exact, 2-tailed). In comparison to structural mutations or to the absence of mutations in the core domain, DNA contact mutations were associated with higher tumour stages (84.6% vs 62%), a higher incidence of lymph node metastasis (91.7% vs 56%; P=0.014, Fisher's exact, 2-tailed), a shortened recurrence-free survival (8.1 months vs 23.7 months, P=0.047, log rank test) and overall survival (11 months vs 29.2 months; P=0.003, log rank test). The latter was also the case when only stage IV tumours were analysed (P=0.0055, log rank test). These data indicate that in HNSCC, TP53 DNA contact mutations confer a strong selection pressure to eliminate wild-type alleles, and that they result in an accelerated tumour progression and reduced therapeutic responsiveness.

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Prognostic significance of TP53 alterations in breast carcinoma

Cited by 155 publications

References 40 publications

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Suppression of apoptosis by bcl-2 does not prevent p53-mediated control of experimental metastasis and anchorage dependence

TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer

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