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Circulating MMP2 and MMP9 in breast cancer—Potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories
Author(s) -
Somiari Stella B.,
Somiari Richard I.,
Heckman Caroline M.,
Olsen Cara H.,
Jordan Rick M.,
Russell Stephen J.,
Shriver Craig D.
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21989
Subject(s) - mmp2 , breast cancer , medicine , cancer , gastroenterology , atypical hyperplasia , metastasis , oncology
Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and metastasis, and increased levels occur in serum and plasma of breast cancer (BC) patients. It is, however, unclear whether changes in serum levels can be exploited for early detection or classification of patients into different risk/disease categories. In our study, we measured concentration and activity of MMP2/9 in sera of 345 donors classified as low risk (Gail score <1.7), high risk (HR) (Gail score ≥1.7), benign disease or BC. Kruskal–Wallis and Mann–Whitney nonparametric tests showed that total‐MMP2 concentration is higher in HR compared to control ( p = 0.012), benign ( p = 0.001) and cancer ( p = 0.007). Active MMP2 (aMMP2) concentration is higher in control than benign and cancer ( p < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than benign ( p < 0.001, p = 0.002, respectively). Total‐MMP2 and total‐MMP9 activities are lower in control than benign ( p < 0.001, p = 0.002, respectively) and cancer ( p < 0.001, respectively). Total‐MMP2 and MMP9 activities are also higher in cancer than benign ( p = 0.004, p < 0.001) and HR ( p = 0.008, p = 0.007, respectively). These results were not affected by age or inclusion/exclusion of donors with noninvasive cancer or atypical hyperplasia. Linear discriminant analysis revealed that HR donors are characterized by lower total‐MMP2 and higher aMMP2. Overall group classification accuracy was 64.5%. Independent validation based on the leave‐one‐out cross validation approach gave an overall classification of 63%. Our study provides evidence supporting the potential role of serum MMP2/9 as biomarkers for breast disease classification. © 2006 Wiley‐Liss, Inc.