Differential Expression of Caspase-3 and Ki-67 in Hereditary Gingival Fibromatosis and Inflammatory Gingival Hyperplasia.

Abstract

Objective: The nuclear protein Ki-67 and caspase-3 regulate cell proliferation and apoptosis as well as the preservation of tissue homeostasis in response to genetic and inflammatory signals that have a role in the pathogenesis of different conditions such as gingival overgrowth. Yet, the distinct pathogenesis of these lesions could be determined by variations in cellular homeostasis mechanisms. The aim of this study was to assess and compare the immunohistochemical expression of Ki-67 and caspase-3 in hereditary gingival fibromatosis (HGF) and inflammatory gingival hyperplasia (IGH), measure quantitative histopathological parameters, and investigate their association with the balance of proliferation and apoptosis underlying these different gingival overgrowth forms.

Materials and methods: An observational cross-sectional study involved 31 gingival biopsies collected from subjects with a history of recurrent gingival enlargement, 15 subjects (9 females and 6 males, 11-46 years) with moderate/severe IGH and 16 subjects with HGF (12 females and 4 males, 16-59 years) during gingivectomy and flap procedures. Anti-caspase-3 antibody and anti-Ki-67 antibody were utilized for immunohistochemistry staining. Imaging was performed at 400× magnification using a light microscope (Olympus BX51 model) equipped with an Olympus XC10-IR color camera; digital images were taken and saved in Joint Photographic Experts Group (JPEG) format. Computer-assisted image analysis was conducted using Q Path software version 0.5.1, an open-source software for digital pathology, to quantify marker expression in tissue sections.

Statistical analysis: Mann-Whitney U-test evaluated expression levels; Spearman's correlation assessed biomarker association. Significance was set at p <0.05.

Results: The present finding revealed that the percentage of caspase-3-positive cells was higher in HGF (mean rank: 21.44) compared with IGH (mean rank: 10.20), with a statistically significant difference (U = 33.000, p < 0.001). Similarly, the H-score for caspase-3 expression was markedly elevated in HGF (mean rank: 21.25) compared with IGH (mean rank: 10.40), with a statistically significant difference (U = 36.000, p < 0.001). However, the proportion of Ki-67-positive cells was significantly greater in HGF (mean rank: 21.31) than in IGH (mean rank: 10.33), with a statistically significant difference (U = 35.000, p < 0.001). In contrast, the evaluation of optical density revealed higher values in IGH (mean rank: 20.07) compared with HGF (mean rank: 12.19); this difference was statistically significant (U = 59.000, p = 0.016).

Conclusions: The findings of this study indicate that both groups reflect divergent pathobiological mechanisms. Specifically, HGF appears to involve genetically mediated tissue remodeling accompanied by compensatory apoptotic activity, while IGH is correlated with inflammation-driven, focally increased proliferation. Our results suggest that HGF and IGH should be regarded as biologically distinct entities.