Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancer

Stenmark-Askmalm, Marie; Stål, Olle; Sullivan, S.; Ferraud, Lilianne; Sun, Xiao‐Feng; Carstensen, John; Nordenskjöld, Bo

doi:10.1016/0959-8049(94)90082-5

Cited by 62 publications

(36 citation statements)

References 23 publications

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“…Cellular p53 accumulation, irrespective of nuclear or cytoplasmic location, has been shown to add prognostic information in stage II breast cancer (Stenmark-Askmalm et al, 1994). In this study no additional prognostic value for p53 in sbge I bha cancer M Stenmark-Askmalm et al 717 cytoplasmic overexpression was found.…”

Section: Results P53 Accumulationcontrasting

confidence: 47%

“…In order to unveil this group of tumours that recur much work has been done to find reliable prognostic factors that can predict which patients would benefit from adjuvant therapy (McGuire et al, 1990). A potential prognostic factor in breast cancer is the accumulation of the tumour-suppressor protein p53 (Isola et al, 1992;Thor et al, 1992;AlIred et al, 1993;Silvestrini et al, 1993;Stenmark-Askmalm et al, 1994). In case of DNA damage, active p53 regulates the cell cycle, giving time for repair or, if this fails, induces apoptosis.…”

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confidence: 99%

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p53 as a prognostic factor in stage I breast cancer

Stenmark-Askmalm

Stål²,

Olsen³

et al. 1995

Br J Cancer

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SinaryAccumulation of the tumour-suppressor protein p53 in breast cancer is associated with several prognostic factors that indicate an aggressive, rapidly proliferating tumour with an unstable genome. To assess p53 accumulation in stage I breast cancer and to evaluate the prognostic value of both nuclear and cytoplasmic p53, 205 patients with node-negative breast cancer and tumour size Ess than or equal to 20 mm were examined. Immunohistochemistry was performed on frozen sections with the monoclonal antibodies PAb 1801 and DOI. Cllular p53 accumulation, within either the nucleus or the cytoplasm or in both, showed the same association with different pathobiological variables as nuclear accumulation alone. Eklven per cent of the tumours showed strong nuclear accumulation and were significantly correlated to age under 50 years, negative oestrogen receptor status, DNA aneuploidy, high S-phase fraction, high pathological grade and poor prognosis. The distant recurrence rate ratio was 6.2 (P=0.002). It is thus concluded that p53 accumulation is of prognostic value in early stage breast cancer.

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Section: Results P53 Accumulationcontrasting

confidence: 47%

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confidence: 99%

p53 as a prognostic factor in stage I breast cancer

Stenmark-Askmalm

Stål²,

Olsen³

et al. 1995

Br J Cancer

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“…In fact, other workers have found p53 alterations to be associated with late stage (Thor et al, 1992;Andersen et al. 1993;Stenmark-Askmalm et al, 1994), high grade (Thor et al, 1992;Silvestrini et al, 1993), comedo, medullary or ductal histological types (Marchetti et al, 1993;O'Malley et al, 1994), negative steroid receptor status (Horak et al, 1991;Isola et al, 1992;Poller et al, 1992), expression of cathepsin D (Domagala et al, 1993), EGFR (Barbareschi et al, 1992;Gasparini et al, 1994) or HER-2/neu (Isola et al, 1992;Poller et al, 1992;Andersen et al, 1993), elevated S-phase fraction (Lipponen et al, 1993;Meyer and He, 1994) and aneuploid DNA content (Isola et al, 1992;StenmarkAskmalm et al, 1994). In the vast majority of these studies, immunohistochemical approaches to detect p53 protein, or more rarely single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing, were used.…”

Section: Resultsmentioning

confidence: 99%

Immunofluorometric analysis of p53 protein and prostate-specific antigen in breast tumours and their association with other prognostic indicators

Levesque

Gm²,

Yu³

et al. 1995

Br J Cancer

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Suman Mutation and overexpression of p53 occurs in 20-40% of breast cancers and has been shown to be an independent prognostic indicator. Recently we have demonstrated prostate-specific antigen (PSA) expression in breast tumours to be suggestive of favourable prognosis, but quantitative relationships between PSA and p53. and between these and other prognostic factors in breast cancer, have not been investigated. Time-resolved immunofluorometric procedures were used to quantify both p53 protein and PSA in 200 breast tumour extracts, which were also assayed for oestrogen (ER) and progesterone receptors (PGR), epidermal growvth factor receptors (EGFR). cathepsin D and HER-2 neu, and characterised for S-phase fraction and DNA ploidy. Weak Spearman correlations were found between p53 and ER (r = -0.18, P = 0.010), PGR (r = -0.15. P = 0.0385) and S-phase fraction (r = 0.17. P = 0.016). while PSA was correlated only with PGR (r = 0.16. P = 0.025). Wilcoxon rank sum analysis revealed that levels of ER (P = 0.0001), PGR (P = 0.0001).S-phase fraction (P = 0.0001) and EGFR (P= 0.0014) differed significantly between the two groups categorised as p53 negative or p53 positive. Tumours classifed as PSA negative or PSA positive were found to differ with respect to PGR (P =0.0091) and S-phase fraction (P = 0.011) in a similar analysis. Contingency tables indicated significant negative associations betweeh the status of p53 and that of ER (P = 0.003) and PGR (P =0.001) and between PSA and S-phase fraction (P = 0.012). and positive associations between p53 and EGFR (P = 0.017), HER-2 neu (P = 0.008). S-phase fraction (P = 0.001) and aneuploidy (P= 0.007), and between PSA and both ER (P = 0.061) and PGR (P = 0.010). No significant associations were found between p53 and PSA. Our results demonstrate that the presence of p53 in breast tumours relates to several other variables which are suspected to predict aggressive tumour phenotypes and that the presence of PSA relates to variables associated with good prognosis.

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“…p53 in tumour tissue has been clearly demonstrated as a prognostic marker in breast cancer (Davidoff et al, 1991a;Ostrowski et al, 1991;Hanzal et al, 1992;Isola et al, 1992;Thor et al, 1992;Allred et al, 1993a, b;Barnes et al, 1993;Noguchi et al, 1993;Silvestrini et al, 1993;Stenmark-Askmalm et al, 1994). Increased p53 protein amounts in tumour cells are indicative of mutated p53 (Davidoff et al, 1991b).…”

Section: Discussionmentioning

confidence: 99%

Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study

et al. 1999

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To perform an epidemiological evaluation of the predictive value of p53 autoantibodies in breast cancer, we measured antibodies against p53 in serum samples from 165 breast cancer patients in comparison with serum samples from 330 healthy controls, selected from the same population as the cases and matched for age, sex and specimen storage time. Median age of patients was 51 years (range 25–64 years). Presence of serum p53 autoantibodies was analysed by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. The lower ELISA reactivities were similar for cases and controls, but presence of high-level reactivity was more common among cases than among controls [odds ratio (OR) 9.03, 95% confidence interval (CI) 2.40–50.43]. Presence of Western blot-detected p53 autoantibodies had a very similar association (OR 10.8, CI 3.0–59.4). Among the cases, we also studied whether there was any correlation between level of anti-p53 antibodies and stage of the disease or survival. There was no significant correlation between presence of antibodies and stage of the disease. There was a significant negative correlation between presence of p53 antibodies and survival ( P = 0.003). A stepwise multivariate Cox regression analysis showed that T-stage, age and presence of anti-p53 antibodies were significant independent prognostic variables, with a dose-dependent negative effect on survival for all three variables. We conclude that presence of anti-p53 antibodies are of significance both for the risk of having breast cancer and the risk of dying from breast cancer. 1999 Cancer Research Campaign

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Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancer

Cited by 62 publications

References 23 publications

p53 as a prognostic factor in stage I breast cancer

p53 as a prognostic factor in stage I breast cancer

Immunofluorometric analysis of p53 protein and prostate-specific antigen in breast tumours and their association with other prognostic indicators

Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study

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