The expression of P16 and S100 associated with elastin degradation and fibrosis of the Ligamentum Flavum hypertrophy

Abstract

BackgroundOne of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). However, the biochemical factors that cause these histologic changes is unclear. P16 and S100 participate in scar formation and collagen development in wound healing and fibrosis diseases. In this study, we investigate the association between P16 and S100 expression and the fibrosis of the hypertrophic LF in LSS.MethodsThe LF specimens were surgically obtained from 30 patients with single-segment LSS (SLSS), 30 patients with double-segment LSS (DLSS) and 30 patients with L4/5 lumbar disc herniation (LDH). The LF thickness was measured by axial T1-weighted MRI. The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (HE) and Verhoff’s Van Gieson’s (VVG) stain, respectively. The localization of P16 and S100 was determined by immunohistochemistry.ResultsThe Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The elastic tissue from the dorsal aspect to the dural aspect in SLSS and DLSS groups was significantly increased. The amount of collagen deposition and elastic tissue is significantly higher in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The specimens in the DLSS group showed positive staining of P16, especially in the dorsal layer. Almost all samples in the SLSS group were partially positive for P16. The LDH group showed negative staining of P16 in both the dural and dorsal layers. All the three groups were stained with S100 in the dorsal layer of the LF. On the contrary, S100 staining was absent in the dural layer of the LF in the three groups.ConclusionsElastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. Increased expression of P16 associated with LF fibrosis and thickness, suggested that the expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with high expression of S100.

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

“…In our previous study, we used imaging and histological methods to grade the degree of LF elastin fibrosis, and an immunohistochemical method was used to detect the expression of P16 and S100 in ventral and dorsal LF. We found that the expression of P16 may be related to LF hypertrophy [8].…”

“…This may be due to LF being subjected to more stress from changes in living habits in recent years and possibly related to race [10]. In the previous study, we measured the absolute and relative thickness of LF and found that the thickness of LF in DLSS group and SLSS group was significantly higher than that in LDH group [8]. In this study, we further investigated the correlation between the thickness of LF and the expression of P16 and S100.…”

“…The measurement method of LF was done as in our previous study [8]. We consider the ligamentum flavum> 3 mm as hypertrophy of ligamentum flavum in imaging measurement.…”

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

“…The measurement method of LF was done as in our previous study [8]. Relative thickness of LF (RT) was calculated as the percentage of the thickness of LF to the oblique diameter of lumbar spinal canal.…”

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

“…The measurement method of LF was done as in our previous study [8]. We consider the ligamentum The average of three independent measurements of three surgeons were taken to determine the relative thickness of a single sample.…”