Deciphering The Angiogenic and Inflammatory Profiles of Gingival Enlargement in Adolescents: An Immunohistochemical Study

Abstract

Background:
Gingival enlargement in adolescents may involve complex inflammatory and vascular tissue responses, but the relationship between angiogenesis and local inflammation remains incompletely characterized. This study evaluated the expression of angiogenic and inflammatory markers in gingival enlargement tissues and examined their associations with histopathological inflammatory changes.

Materials & Methods:

A comparative study was conducted among 60 adolescents, comprising 30 participants with clinically evident gingival enlargement and 30 age- and sex-matched healthy controls. Gingival tissue specimens were evaluated histopathologically and by immunohistochemistry. Vascular endothelial growth factor (VEGF) and CD34-positive microvessel density (MVD) were assessed as indicators of angiogenic activity, while interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were evaluated as inflammatory markers. Immunohistochemical expression was assessed using H-scores, staining intensity, and marker positivity. Correlation and multivariable analyses were performed to examine relationships between marker expression and gingival enlargement.

Results:
The gingival enlargement group demonstrated significantly higher gingival enlargement, inflammatory infiltrate, vascularity, and fibrosis scores than the control group probability (p<0.001 for all). VEGF expression was significantly greater in the gingival enlargement group (186.4 ± 31.8) than in controls (92.7 ± 24.6; p<0.001), while CD34-positive MVD was also higher (28.6 ± 6.7 vs. 17.4 ± 4.9 vessels/ high-power field (HPF); p<0.001). Similarly, IL-6 and TNF-α H-scores were significantly elevated in gingival enlargement specimens (171.8 ± 35.2 vs. 79.6 ± 22.8 and 159.3 ± 33.7 vs. 72.4 ± 20.9, respectively; p<0.001). VEGF and CD34 positivity, as well as IL-6 and TNF-α positivity, were significantly more frequent in the gingival enlargement group. Significant positive correlations were observed between VEGF and CD34 MVD (r=0.68, p<0.001), VEGF and IL-6 (r=0.59, p=0.001), and VEGF and TNF-α (r=0.54, p=0.002). IL-6 demonstrated the strongest correlation with the histopathological inflammatory infiltrate score (r=0.73, p<0.001). Multivariable analysis showed that VEGF, CD34 MVD, IL-6, and TNF-α remained independently associated with gingival enlargement.

Conclusion:
Gingival enlargement in adolescents is characterized by increased angiogenic and inflammatory activity, accompanied by greater vascularity, inflammatory infiltration, and fibrosis. The significant associations among VEGF, CD34, IL-6, and TNF-α suggest an interconnected angiogenic–inflammatory response that may contribute to the histopathological changes observed in gingival enlargement.