Fibulin-4 expression in potentially malignant disorders and squamous cell carcinoma of oral mucosa-An immunohistochemical study.

Background: Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths, with India accounting for approximately one-fourth of global cases. OSCC often develops from oral potentially malignant disorders like leucoplakia, erythroplakia, and oral submucous fibrosis (OSF), each carrying varying risks for malignant transformation. Fibulin-4, a glycoprotein involved in extracellular matrix (ECM) remodelling, has been implicated in several cancers, but its role in oral tumours remains unexplored.

Methodology: Paraffin-embedded sections of oral epithelial dysplasia (OED) (n = 24), OSF (n = 23), OSCC (n = 23), and normal mucosa (n = 23) were analysed for immunohistochemical expression of Fibulin-4. Staining intensity and percentage of positive cells were evaluated with a semi-quantitative scoring system. Statistical analyses included Kruskal-Wallis, Chi-square, Mann-Whitney tests, and Kappa statistics to assess interobserver and intraobserver variability.

Results: Significant differences in Fibulin-4 expression were noted across groups. OSCC and OED displayed high proportions of strong Fibulin-4 expression (76-100%), while OSF showed distinct staining patterns mainly in the middle and upper tissue layers. Higher grades of staining intensity were observed in leucoplakia (82.6% were grade 2), OSMF (83.3% were grade 2), and OSCC groups (65.2% were grade 2) than the control group (78% were grade 1). The interobserver reliability and interobserver reproducibility of Fibulin-4 expression evaluated by kappa statistic was excellent( kappa ≥ 0.80). Fibulin-4 expression was high in OSCC, OED, OSF compared to normal oral mucosa and was statistically significant (p<0.001).

Conclusion: Fibulin-4 expression varies significantly across normal mucosa, OED, OSF, and OSCC, suggesting its potential role in oral carcinogenesis and ECM dynamics. Elevated Fibulin-4 expression in OSCC and OED highlights its potential as a biomarker for malignant transformation. Further research is needed to clarify its role and explore its potential as a therapeutic target in oral cancer.