A critical influence of HIF-1 on MMP-9 and Galectin-3 in oral lichen planus.

OBJECTIVE: Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease. SUBJECTS AND METHODS: The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group. RESULTS: Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252). CONCLUSION: These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.

Correlation of VEGF and MMP-2 levels in oral lichen planus: An in vivo immunohistochemical study.

BACKGROUND: This study aimed to investigate the relation between vascular endothelial growth factors (VEGF) and matrix metalloproteinase-2 (MMP-2) in different oral lichen planus (OLP) forms compared to control patients. METHODS: Biopsies from 60 patients were selected and equally distributed as follows: reticular/popular OLP (R/PLP), atrophic/erosive OLP (A/ELP) patients, healthy subjects (Control). All biopsies were immune-histochemical stained and statistically analyzed for VEGF and MMP-2 expression. RESULTS: Immune-expression of VEGF was significant between OLP and control (P-value <0.001). OLP showed a higher epithelial expression of VEGF in A/ELP compared to R/PLP (15.19 ± 2.53). In connective tissue (CT), R/PLP showed a higher VEGF expression (11.57 ± 2.32) compared to A/ELP (9.87 ± 2.48); (p < 0.001), with no significant difference (P-value ≥ 0.05). A significant epithelial expression of MMP-2 was seen in A/ELP compared to R/PLP (21.32 ± 7.08). R/PLP showed a higher expression of MMP-2 (20.45 ± 6.28) in CT compared to A/ELP group (17.66 ± 6.94), with a non-significant difference (P-value = 1.000). In A/ELP, a positive correlation between VEGF and MMP-2 was detected in CT, r = 0.761, with a weak correlation was noticed in epithelium r = 0.163. A negative correlation was noted between VEGF and MMP-2 in R/PLP in CT, r = -0.368, with a moderate positive correlation in epithelium, r = 0.655. CONCLUSION: MMP-2 and VEGF protein profiles support a role in the pathogenesis of OLP. Based the MMP-2 and VEGF findings in the A/ELP group, this pathway may have a role in the malignant transformation of these lesions. Both observations invite further study.

Expression of CD163 in hereditary gingival fibromatosis: A possible association with TGF-ß1.

BACKGROUND: Although several studies have discussed some of the molecular and cellular changes associated with hereditary gingival fibromatosis (HGF), its pathogenesis is still largely unclear. This study was directed to detect and outline the degree of relationship between the immunophenotyped macrophages (M2) expressing CD163 and TGF-ß1 in patients with gingival overgrowth due to HGF. METHODS: Biopsies from 20 patients suffering from HGF and 20 normal control subjects were harvested, histologically and immunohistochemically stained then, analyzed and statistically compared and correlated for CD163 immunoexpression and TGF-ß1. RESULTS: All HGF specimens expressed TGF-ß1 by most of the connective tissue fibroblasts, with statistically high significant mean of area % (2.61 ± 0.41) compared to normal controls (0.11 ± 0.06; P = .001). All control specimens revealed negligible CD163 immunostaining of the few inflammatory cells found with a mean area of % (0.69 ± 0.12), while the specimens of HGF cases showed statistically significant higher CD163 expression (3.39 ± 0.75) at (P = .007). A statistically significant higher mean % of M2 cells expressing CD163 in relation to the total number of the inflammatory cells was revealed in HGF (34.46 ± 2.04) compared to the control group (16.36 ± 2.39; P-value ≤ .05). Moderate correlation between CD163 and TGF-ß1 was detected in HGF (r = .451; P-value < .05). CONCLUSIONS: CD163 and TGF-ß1 were clearly expressed in HGF cases compared to healthy control patients, with significant correlation. In HGF, the increase in CD 163-positive cells was specific and not dependent on the chronic gingival inflammation.