Urinary Metalloproteinases: Noninvasive Biomarkers for Breast Cancer Risk Assessment
Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status,...
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Published in | Cancer epidemiology, biomarkers & prevention Vol. 17; no. 5; pp. 1034 - 1042 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.05.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast
cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases
as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia
and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS,
and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with
monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of
atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated
in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing
an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed
using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction
index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive
detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification
of women at increased risk of developing breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1034–12) |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1055-9965 1538-7755 |
DOI: | 10.1158/1055-9965.EPI-07-0365 |