p53 as an Independent Prognostic Marker in Lymph Node-Negative Breast Cancer Patients (original) (raw)
Journal Article
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
Correspondence to : Rosella Silvestrini, Ph.D., Oncologia Sperimentale C, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy.
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
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Istituto di Biometria, Università degli Studi
Milan
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
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Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori and Centro di Studio sulla Patologia Cellulare del CNR
Milan
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Direzione Generale, Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy
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Received:
23 November 1992
Revision received:
10 March 1993
Cite
Rosella Silvestrini, Elvira Benini, Maria Grazia Daidone, Silvia Veneroni, Patrizia Boracchi, Vera Cappelletti, Giovanni Di Fronzo, Umberto Veronesi, p53 as an Independent Prognostic Marker in Lymph Node-Negative Breast Cancer Patients, JNCI: Journal of the National Cancer Institute, Volume 85, Issue 12, 16 June 1993, Pages 965–970, https://doi.org/10.1093/jnci/85.12.965
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Abstract
Background:
At present, most decisions concerning the use of adjuvant therapy in lymph node-negative breast cancer patients are made on the basis of traditional factors such as tumor size, nodal status, and histopathologic features. However, prognostic factors are being investigated that could identify high-risk groups and that could better address treatment efforts for those patients. Identification of more accurate prognostic markers, such as the expression of the mutant p53 protein encoded by the p53 (also known as TP53) tumor suppressor gene, that are reproducible, easily assessable, and independent in predicting clinical outcome would have a beneficial impact on cancer treatment decisions. Purpose : Our Purpose was to analyze the predictive relevance of mutant p53 protein expression on 6-year relapse-free and overall survival in node-negative breast cancer patients in relation to menopausal status, tumor size, cell kinetics, and estrogen receptor status. Methods : Expression of mutant p53 protein was detected by an immunohistochemical technique using a 1: 50 dilution of PAb1801 monoclonal antibody on paraffin-embedded tumor specimens obtained from 256 axillary lymph nodenegative breast cancer patients, with long-term follow-up (median, 72 months). The [ 3 H]thymidine labeling index, a measure of cell kinetics, was evaluated on histologic sections after fresh tumor tissue was labeled with [ 3 H]thymidine. Estrogen receptor status was determined by the dextran-coated charcoal absorption technique. Statistical comparisons were made for levels of p53 protein expression, [ 3 H]thymidine labeling index, estrogen receptor status, tumor size, and menopausal status with respect to 6-year relapse-free survival and overall survival. Results : Overexpression of the p53 protein, defined as the presence of more than 5% positive cells, was detected in 113 (44%) of 256 tumors. Odds ratios (ORs) for multiple regression analysis of 6-year relapse-free survival were significantly higher for p53 (OR = 3.24; 95% confidence limits [CL] = 2.01–5.23) and [3H]thymidine labeling index (OR = 1.92; 95% CL = 1.19–3.12), both of which appeared to be the most relevant indicators of relapse, than for tumor size (OR = 1.49; 95% CL = 0.94–2.38) and estrogen receptor status (OR = 0.91; 95% CL = 0.55–1.51). Overexpression was found to be unrelated to menopausal status. Conclusions : Immunohistochemically detected p53 overexpression is an independent marker for shortened 6-year relapse-free and overall survival in node-negative patients with resectable breast cancers. Based on these findings, p53 overexpression should be used with other established prognostic factors, such as [ 3 H]thymidine labeling index and estrogen receptor status, to further refine the prognostic assessment of node-negative breast cancer. [J Natl Cancer Inst 85: 965–1970, 1993]
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Topic:
- menopause
- process of absorption
- cancer
- monoclonal antibodies
- axilla
- charcoal
- follow-up
- tumor suppressor genes
- lymph
- paraffin
- protein p53
- estrogen receptors
- thymidine
- kinetics
- neoplasms
- patient prognosis
- treatment outcome
- breast cancer
- adjuvant therapy
- cancer therapy
- dextran
- prognostic marker
- protein overexpression
- prognostic factors
- dilution technique
- dilute (action)
- tumor size
- histopathology tests
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