MDM2 protein expression is a negative prognostic marker in breast carcinoma
The protein encoded by the MDM2 oncogene inhibits the function of p53, leading to increased cell growth, avoidance of apoptosis, tolerance of genetic instability, and resistance to chemotherapy. The present study was performed to evaluate the relationship between MDM2 protein expression and survival...
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Published in | Modern pathology Vol. 19; no. 1; pp. 69 - 74 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
Elsevier Inc
01.01.2006
Elsevier Limited |
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Abstract | The protein encoded by the MDM2 oncogene inhibits the function of p53, leading to increased cell growth, avoidance of apoptosis, tolerance of genetic instability, and resistance to chemotherapy. The present study was performed to evaluate the relationship between MDM2 protein expression and survival in breast carcinoma. Two series of cases were used in this study: the first to identify the cutoff to be used in the interpretation of MDM2 immunostaining and perform preliminary survival analysis, and a second, independent series, to validate the findings from the first series and to perform multivariate analysis. For both series, archival sections of tissue microarrays were stained with anti-MDM2 antibody (NeoMarkers, Fremont, CA, USA) and MDM2 staining intensity was scored semiquantitatively. In the first series, 49 of 362 (14%) interpretable cases were positive for MDM2 expression, with 35 (10%) showing weak positivity and 14 (4%) strong positivity. Patients with MDM2-positive tumours had a significantly worse disease-specific survival than patients with MDM2-negative tumours (P=0.0022, 10-year DSS 61% (95% CI: 45–73) vs 73% (95% CI: 67–77)). No significant difference in survival was observed between patients with strongly and weakly MDM2-positive tumours (P=0.3). Accordingly, in the independent validation series weak and strong MDM2 positivity were combined and considered to be MDM2 positive. MDM2 expression was seen in 230/1747 (13%) interpretable cases in this series, with a significant difference (P<0.0001) in DSS between MDM2-negative and MDM2-positive cases (10 year DSS 58% (95% CI: 51–64) vs 73% (95% CI: 70–75)). MDM2 was an independent prognostic marker (HR=1.35, P=0.02) in a Cox regression model including MDM2 expression, tumour grade, nodal status, ER status and tumour size. Immunohistochemical studies of MDM2 in more than 2000 breast carcinomas show that MDM2 is an independent negative prognostic marker. |
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AbstractList | The protein encoded by the MDM2 oncogene inhibits the function of p53, leading to increased cell growth, avoidance of apoptosis, tolerance of genetic instability, and resistance to chemotherapy. The present study was performed to evaluate the relationship between MDM2 protein expression and survival in breast carcinoma. Two series of cases were used in this study: the first to identify the cutoff to be used in the interpretation of MDM2 immunostaining and perform preliminary survival analysis, and a second, independent series, to validate the findings from the first series and to perform multivariate analysis. For both series, archival sections of tissue microarrays were stained with anti-MDM2 antibody (NeoMarkers, Fremont, CA, USA) and MDM2 staining intensity was scored semiquantitatively. In the first series, 49 of 362 (14%) interpretable cases were positive for MDM2 expression, with 35 (10%) showing weak positivity and 14 (4%) strong positivity. Patients with MDM2-positive tumours had a significantly worse disease-specific survival than patients with MDM2-negative tumours (P=0.0022, 10-year DSS 61% (95% CI: 45–73) vs 73% (95% CI: 67–77)). No significant difference in survival was observed between patients with strongly and weakly MDM2-positive tumours (P=0.3). Accordingly, in the independent validation series weak and strong MDM2 positivity were combined and considered to be MDM2 positive. MDM2 expression was seen in 230/1747 (13%) interpretable cases in this series, with a significant difference (P<0.0001) in DSS between MDM2-negative and MDM2-positive cases (10 year DSS 58% (95% CI: 51–64) vs 73% (95% CI: 70–75)). MDM2 was an independent prognostic marker (HR=1.35, P=0.02) in a Cox regression model including MDM2 expression, tumour grade, nodal status, ER status and tumour size. Immunohistochemical studies of MDM2 in more than 2000 breast carcinomas show that MDM2 is an independent negative prognostic marker. |
Author | Gelmon, Karen A Yorida, Erika Bajdik, Chris D Cheang, Maggie C U Huntsman, David G Nielsen, Torsten O Turbin, Dmitry A De Luca, Alessandro Gilks, C Blake |
Author_xml | – sequence: 1 givenname: Dmitry A surname: Turbin fullname: Turbin, Dmitry A organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 2 givenname: Maggie C U surname: Cheang fullname: Cheang, Maggie C U organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 3 givenname: Chris D surname: Bajdik fullname: Bajdik, Chris D organization: Cancer Control Research Program, British Columbia Cancer Agency, Vancouver, BC, Canada – sequence: 4 givenname: Karen A surname: Gelmon fullname: Gelmon, Karen A organization: Division of Medical Oncology and Breast Tumour Group, British Columbia Cancer Agency, Vancouver, BC, Canada – sequence: 5 givenname: Erika surname: Yorida fullname: Yorida, Erika organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 6 givenname: Alessandro surname: De Luca fullname: De Luca, Alessandro organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 7 givenname: Torsten O surname: Nielsen fullname: Nielsen, Torsten O organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 8 givenname: David G surname: Huntsman fullname: Huntsman, David G organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada – sequence: 9 givenname: C Blake surname: Gilks fullname: Gilks, C Blake email: Blake.Gilks@vch.ca organization: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre at the Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16258514$$D View this record in MEDLINE/PubMed |
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Keywords | tissue microarrays MDM2 protein survival analysis breast carcinoma |
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SubjectTerms | Biomarkers Biomarkers, Tumor - analysis Breast cancer breast carcinoma Breast Neoplasms - metabolism Breast Neoplasms - pathology Cyclin E - analysis Female Gene amplification Humans Immunohistochemistry - methods Immunohistochemistry - statistics & numerical data Keratin-5 Keratin-6 Keratins - analysis Ki-67 Antigen - analysis MDM2 protein Pathology Prognosis Proportional Hazards Models Protein expression Proteins Proto-Oncogene Proteins c-mdm2 - biosynthesis Receptor, ErbB-2 - analysis Receptors, Estrogen - analysis Reproducibility of Results Survival Analysis Tissue Array Analysis - methods Tissue Array Analysis - statistics & numerical data tissue microarrays Tumor Suppressor Protein p53 - analysis Tumors |
Title | MDM2 protein expression is a negative prognostic marker in breast carcinoma |
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