Abstract
Certain matrix metalloproteinases (MMPs) have the ability to degrade collagen IV, a main component of the breast lobular basement membrane. In this cross-sectional study, we evaluated expression of MMPs 2, 9, and 14 and collagen IV in LCIS and adjacent normal breast tissue among LCIS patients without invasive breast cancer to determine whether expression differed between benign and preinvasive breast epithelial tissue. A total of 64 LCIS patients, diagnosed 2004–2014, were included; 44 had sufficient paired normal tissue for analysis. Marker epithelial expression was measured using immunofluorescence and quantified using the H score (MMPs) or pixel intensity (collagen IV). Associations were evaluated using the Spearman correlation or the Wilcoxon signed-rank test. In LCIS and normal tissue, there was a strong correlation between MMP2 and MMP14 expression (LCIS r = 0.69, normal r = 0.81, both P < 0.01). Other pairwise correlations were moderate to weak (range: LCIS r = 0.32–0.47, normal r = 0.19–0.32). For all markers, expression was lower in LCIS vs. normal tissue (all P ≤ 0.05). In sum, collagenase MMPs were expressed in normal breast and LCIS lesions of LCIS patients. However, expression was not higher in LCIS compared with normal tissue, suggesting collagenase MMP expression does not increase as breast tissue gains a more proliferative phenotype.
Highlights
Women with lobular carcinoma in situ (LCIS) have an estimated 6 to 11-fold increased risk of invasive breast cancer compared with the general population[1,2,3]
MMP2, MMP9, and MMP14 expression was common in LCIS: 98% of samples expressed MMP2, 86% expressed MMP9, and 100% expressed MMP14
It has been proposed that some LCIS are non-obligatory precursors of invasive lobular breast cancer[4,5], suggesting that the biological determinants of breast cancer are present at the in situ stage
Summary
Women with lobular carcinoma in situ (LCIS) have an estimated 6 to 11-fold increased risk of invasive breast cancer compared with the general population[1,2,3]. Much of the existing data regarding MMP expression in LCIS and normal breast tissue comes from convenience samples obtained from patients with invasive breast cancer. We conducted a pilot study to estimate quantitative expression of MMP2, MMP9, MMP14, and collagen IV in archival tissues from women diagnosed with LCIS without invasive breast cancer.
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