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Quantitative expression of MMPs 2, 9, 14, and collagen IV in LCIS and paired normal breast tissue
Sarah J Nyante1,2,3, Tengteng Wang4, Xianming Tan5,6
1Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. sarah_nyante@med.unc.edu.
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.
Insights
Matrix metalloproteinases (MMPs) and collagen IV were evaluated in lobular carcinoma in situ (LCIS) and normal breast tissue. MMP expression was lower in LCIS, suggesting it does not increase with a more proliferative phenotype.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Certain matrix metalloproteinases (MMPs) degrade collagen IV, a key breast lobular basement membrane component.
- Understanding MMP and collagen IV expression in preinvasive lesions is crucial for breast cancer progression research.
Purpose of the Study:
- To compare the expression of MMPs 2, 9, and 14, and collagen IV in lobular carcinoma in situ (LCIS) versus adjacent normal breast tissue.
- To determine if collagenase MMP expression increases with the transition to a more proliferative breast epithelial phenotype.
Main Methods:
- Cross-sectional study of 64 LCIS patients with paired normal breast tissue analysis.
- Immunofluorescence used to measure epithelial expression of MMPs and collagen IV.
- Quantification via H score for MMPs and pixel intensity for collagen IV; statistical analysis using Spearman correlation and Wilcoxon signed-rank test.
Main Results:
- Strong correlation observed between MMP2 and MMP14 expression in both LCIS and normal tissue (P < 0.01).
- Expression levels of all evaluated markers (MMPs 2, 9, 14, and collagen IV) were significantly lower in LCIS compared to adjacent normal breast tissue (P ≤ 0.05).
Conclusions:
- Collagenase MMPs are expressed in both normal breast tissue and LCIS lesions.
- The observed lower expression of collagenase MMPs in LCIS does not support the hypothesis that their expression increases as breast tissue becomes more proliferative.
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