Hyaluronan, TSG-6, and inter-α-inhibitor in periprosthetic breast capsules: reduced levels of free hyaluronan and TSG-6 expression in contracted capsules.

Caroline M Milner,Kian T Tan,Anthony J Day,Ardeshir Bayat,Ali Juma,Andrew D Baildam

doi:10.1177/1090820x10391778

Abstract

The exact mechanism of capsular contracture (CC) is still unknown. The covalent modification of hyaluronan (HA) with the heavy chains (HC) of inter-α-inhibitor (IαI) has been identified as an important pathway in inflammation and tissue remodeling, where HC·HA formation is catalyzed by TSG-6 (the protein product of tumor necrosis factor stimulated gene-6). The authors quantitatively assess the correlation between severity of CC (measured by Baker grade) and expression of HA, TSG-6, and IαI (ie, the polypeptides HC1, HC2, and bikunin) in periprosthetic breast capsules. Immunofluorescent staining for HA, TSG-6, HC1, HC2, and bikunin was carried out on periprosthetic breast capsules (n = 7) of each Baker grade from four anatomical locations. Quantitative analysis was performed to identify differences in staining intensity. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine differences in TSG-6 gene expression levels. Severity of contracture was associated with reduced staining for both free HA (Pearson correlation coefficient, r = -0.645, P < .001) and TSG-6 (r = -0.642, P = .002). RT-qPCR showed a significant negative correlation between severity of contracture and TSG-6 gene expression levels (r = -0.750, P = .001). The negative correlation between TSG-6 expression levels and severity of CC suggests a possible protective role for TSG-6 in the context of CC formation, and this may have a clinically relevant role in prevention of breast CC.

Highlights

The exact mechanism of capsular contracture (CC) is still unknown
Bikunin staining associated with fibroblasts appeared more intense than for heavy chain 1 (HC1) or heavy chain 2 (HC2) and was both cell associated and colocalizing with HA (Figure 3D)
There were no significant correlations between HC1, HC2, or bikunin staining intensities with implant age or Baker grade

Summary

Introduction

The exact mechanism of capsular contracture (CC) is still unknown. The covalent modification of hyaluronan (HA) with the heavy chains (HC) of inter-α-inhibitor (IαI) has been identified as an important pathway in inflammation and tissue remodeling, where HC·HA formation is catalyzed by TSG-6 (the protein product of tumor necrosis factor stimulated gene-6). Objective: The authors quantitatively assess the correlation between severity of CC (measured by Baker grade) and expression of HA, TSG-6, and IαI (ie, the polypeptides HC1, HC2, and bikunin) in periprosthetic breast capsules. Methods: Immunofluorescent staining for HA, TSG-6, HC1, HC2, and bikunin was carried out on periprosthetic breast capsules (n = 7) of each Baker grade from four anatomical locations. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine differences in TSG-6 gene expression levels. RT-qPCR showed a significant negative correlation between severity of contracture and TSG-6 gene expression levels (r = −0.750, P = .001). Conclusions: The negative correlation between TSG-6 expression levels and severity of CC suggests a possible protective role for TSG-6 in the context of CC formation, and this may have a clinically relevant role in prevention of breast CC.

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Conclusion