p53 as an Independent Prognostic Marker in Lymph Node-Negative Breast Cancer Patients

Silvestrini, Rosella; Benini, Elvira; Daidone, Maria Grazia; Veneroni, Silvia; Boracchi, Patrizia; Cappelletti, Vera; Fronzo, G. Di; Veronesi, Umberto

doi:10.1093/jnci/85.12.965

Cited by 227 publications

(118 citation statements)

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“…Separation of these by an arbitrarily selected p53 cut-off point was made with considerations of maximising statistical power and of the detection limit of the p53 immunoassay, approximately 0.5 U g'. The choice of 5 U g-' divided specimens into 157 p53-negatives (78%) and 43 p53-positives (22%), rates which are within the range reported by others for breast cancer (Thor et al, 1992;Allred et al, 1993;Silvestrini et al, 1993) but lower than the percentage we found in ovarian cancer using the same immunological procedure (Levesque et al, 1995b). Prostate-specific antigen is a newly demonstrated prognostic factor in breast cancer (Yu et al, 1995) and was found to be present in 26% (n = 52) of the breast cancer tumour specimens assayed in this study when a cut-off for positivity of 0.03 ng mg-was used.…”

Section: Resultssupporting

confidence: 78%

“…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: 94%

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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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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 94%

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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“…A similar observation has been made in soft-tissue sarcomas (Huuhtanen et al, 1996). The prognostic value of immunohistochemically detected erbB-2 and p53 protein in early node-negative breast cancer is controversial (Silvestrini et al, 1993;Ravdin and Chamness, 1995;Rosen et al, 1995). In this study those markers did not show prognostic power for either local or distant recurrence.…”

Section: Discussioncontrasting

confidence: 51%

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

Jahkola

Toivonen²,

Virtanen³

et al. 1998

Br J Cancer

101

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Summary We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.

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“…Specimens were deemed receptor positive if the HSCORE was greater than 100. For the other biological parameters, a cutoff of X5 positive cells was introduced to discriminate p53-positive and p53-negative primary malignancies, as previously reported (Silvestrini et al, 1993). A cutoff of 10% stained cells was considered for c-erbB2 positivity.…”

Section: Immunohistochemical Scoringmentioning

confidence: 99%

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

et al. 2003

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The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen þ tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage 450% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (Po0.01 and o0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l À1 onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, Po0.05) and 13.0 g/dl À1 (81.0 vs 57.6%, Po0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels p13 g dl À1 showed a lower treatmentinduced reduction in Ki67 expression (Po0.04) and a higher Ki67 expression at postoperative evaluation (Po0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism.

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p53 as an Independent Prognostic Marker in Lymph Node-Negative Breast Cancer Patients

Cited by 227 publications

References 0 publications

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

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

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

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