Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy

Bergh, Jonas; Norberg, Torbjörn; Sjögren, S.; Lindgren, Anders; Holmberg, Lars

doi:10.1038/nm1095-1029

Cited by 381 publications

(255 citation statements)

References 18 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…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). p53 protein expression has been identified as a predictor of disease recurrence (Iwaya et al, 1991;Barnes et al, 1993;Friedrichs et al, 1993;Marks et al, 1994), even for patients without nodal involvement at the time of diagnosis (Allred et al, 1993;Barnes et al, 1993;Silvestrini et al, 1993;MacGrogan et al, 1995) and for poor survival (Isola et al, 1992;Allred et al, 1993;Silvestrini et al, 1993;Received 12 March 1997 Revised 25 July 1997 Accepted 21 August 1997 Correspondence to: AM Thompson Elledge and Borg et al, 1995;MacGrogan et al, 1995;Silvestrini et al, 1996).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…There are several problems in using this technique for p53 that relate to a failure to detect all mutations plus assessment of what is positive (Hall and McCluggage, 2006) so the available evidence would favour the use of mutational analysis (Bergh et al, 1995;Aas et al, 1996;Berns et al, 2000). Phosphorylation of p53 at Ser 392 has been shown to be a frequent modification in tumours (Minamoto et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The effect of several chemotherapeutic drugs may be mediated through DNA damage and induction of apoptosis (Gewirtz, 2000), and therefore alterations to TP53 and hence p53 protein function could result in relative resistance to these agents. Studies assessing either immunohistochemically detectable p53 and/or TP53 mutations in breast cancers and response to chemotherapy differ in their findings as to their value as predictors (Bergh et al, 1995;Elledge et al, 1995;Stal et al, 1995;Aas et al, 1996;Thor et al, 1998;Berns et al, 2000;Rahko et al, 2003). However, as apoptosis plays a major role in treatment response, analysis of other apoptotic regulatory gene products, as well as p53, may give additional information.…”

mentioning

confidence: 99%

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

View full text Add to dashboard Cite

Established clinico -pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12 -127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P ¼ 0.001) and survivin (P ¼ 0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo-and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups.

show abstract

“…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). Whether speci®c mutation types have a di erential e ect in HNSCC, has thus far not been examined.…”

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

View full text Add to dashboard Cite

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.

show abstract

Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy

Cited by 381 publications

References 18 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

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

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

Contact Info

Product

Resources

About