Abstract
BackgroundRecent 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.MethodsThe 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.ResultsWomen 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.ConclusionThese 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.
Highlights
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 classified our patients into five groups of increasing disease severity and we evaluated the correlation between the expression of MMP-9, NGAL, and MMP-9/NGAL complex and severity score
NGAL serum levels were similar between women with Ductal carcinoma in situ (DCIS), Atypical ductal hyperplasia (ADH) and sclerosing adenosis whereas a marked increase was observed for women with invasive carcinoma (Table 1)
Summary
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. Stoesz and coworkers originally reported heterogeneous expression of NGAL mRNA and protein levels in breast cancer tissue that significantly correlated with other markers of poor prognosis including estrogen and progesterone receptor-negative status and high proliferation [10]. NGAL remained an independent prognostic marker for diseasefree survival These data suggested that tissue NGAL expression could be a valuable prognostic marker in patients with primary breast cancer [11]. Gene expression profiling studies have confirmed the correlation between NGAL expression and negative estrogen receptor status [18,19,20,21]
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