Microvascular density and hypoxia-inducible factor in intraepithelial vocal fold lesions

The promotion of neovascularisation is a crucial aspect of carcinogenesis. The study evaluates the microvascular density (MVD) and expression of hypoxia-induced factor (HIF-1α) in hypertrophic vocal fold (VF) lesions of different histopathological states including non-dysplastic, low-grade, high-grade dysplasia and invasive glottic cancer.

Histological specimens collected from patients diagnosed and treated in a single centre with different histological grades were immunohistochemically stained with CD31, CD34 and HIF-1α. Of the total number of 77 analysed VF specimens, 20 were non-dysplastic, 20 had low-grade dysplasia, 17 high-grade dysplasia and 20 were invasive cancers.

The highest mean value for MVD evaluated with expression of CD31 (MVD CD31) was 21.23 ± 14.46 and identified in the low-grade dysplasia group. The average MVD CD31 was 13.74 ± 5.56 and 20.11 ± 9.28 in the high-grade dysplasia and invasive cancer group, respectively. The highest MVD evaluated with CD34 (MVD CD34) was revealed for invasive cancer 35.64 ± 17.21. The MVD CD34 was higher for low-grade than in high-grade dysplasia (25.87 ± 12.30 vs 24.65 ± 15.92, respectively). The expression of HIF-1α was strong or very strong in 60% of non-dysplastic lesions, 100% of low-grade dysplasia cases, 53% of high-grade dysplasia cases and 50% of invasive cancer cases. The comparison of MVD CD31 with MVD CD34 revealed a strong positive correlation (ρ value 0.727). The comparison of both MVD CD31 and MVD CD34 with HIF-1α resulted in no linear relationship (ρ value of 0.143 and 0.165, respectively).

The stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.