TY - JOUR

T1 - Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment

AU - Pories, Susan E

AU - Zurakowski, David

AU - Roy, Roopali

AU - Lamb, Carolyn C

AU - Raza, Sughra

AU - Exarhopoulos, Alexis

AU - Scheib, Rochelle G

AU - Schumer, Susan

AU - Lenahan, Corrine

AU - Borges, Virginia

AU - Louis, Gwendolyn W

AU - Anand, Ankur

AU - Isakovich, Nina

AU - Hirshfield-Bartek, Judi

AU - Wewer, Ulla

AU - Lotz, Margaret M

AU - Moses, Marsha A

PY - 2008/5/1

Y1 - 2008/5/1

N2 - 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.

AB - 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.

KW - ADAM Proteins

KW - Analysis of Variance

KW - Breast Neoplasms

KW - Carcinoma in Situ

KW - Case-Control Studies

KW - Chi-Square Distribution

KW - Female

KW - Humans

KW - Logistic Models

KW - Matrix Metalloproteinase 9

KW - Membrane Proteins

KW - Metalloproteases

KW - Middle Aged

KW - Precancerous Conditions

KW - Risk Assessment

KW - Tumor Markers, Biological

U2 - 10.1158/1055-9965.EPI-07-0365

DO - 10.1158/1055-9965.EPI-07-0365

M3 - Journal article

C2 - 18483323

VL - 17

SP - 1034

EP - 1042

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 5

ER -