The Expression of P16 and S100 Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum Hypertrophy
Abstract Background: One of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). 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. Methods: The LF specimens were surgically obtained from thirty patients with single-segment LSS (SLSS) and 30 patients with double-segment LSS (DLSS). 30 patients with L4/5 lumbar disc herniation were included as control. The LF thickness was measured by axial T1-weighted Magnetic Resonance Imaging(MRI). The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (H&E) and Verhoff’s Van Gieson’s (VVG) stain, respectively. The localization of P16 and S100 within the LF tissue was determined by immunohistochemistry. Linear correlation tests between LF thickness, fibrosis, P16 and S100 expression was analyzed. Results: The Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The mean thickness in the DLSS group was 5.658mm (RT = 43.107), compared with 4.924 mm (RT=36.520) and 2.886 mm (RT=21.330), respectively in the SLSS and LDH groups. The amount of collagen deposition is significantly higher in the DLSS group compared with the SLSS and LDH groups (p < 0.05) as shown by the H&E staining. A higher level of elastic tissue was also seen in the DLSS group compared with the SLSS and LDH groups (p < 0.05) though VVG staining. There was a significant correlation between H&E mean rating and relative LF thickness in the DLSS group (r = 0.562; p = 0.010). The specimens in the DLSS group showed positive staining of P16. All the three groups were stained with S100 in the dorsal layer of the LF. Conclusions: Elastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. The expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with S100.