Open Access Highly Accessed Research article

Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease

Xeni Provatopoulou1, Antonia Gounaris1*, Eleni Kalogera, Flora Zagouri2, Ioannis Flessas2, Evgenios Goussetis3, Afroditi Nonni4, Ioannis Papassotiriou5 and George Zografos2

Author Affiliations

1 Research Center, Hellenic Anticancer Institute, Athens, Greece

2 Breast Unit, First Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, Athens, Greece

3 Stem Cell Transplant Unit, "Aghia Sophia" Children's Hospital, Athens, Greece

4 First Department of Pathology, School of Medicine, University of Athens, Athens, Greece

5 Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece

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BMC Cancer 2009, 9:390  doi:10.1186/1471-2407-9-390

Published: 4 November 2009



Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.


The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.


Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.


These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.