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

Abstract

ObjectiveThe 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.Materials and methodsHistological 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.ResultsThe 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).ConclusionThe stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.Electronic supplementary materialThe online version of this article (10.1007/s00405-019-05355-2) contains supplementary material, which is available to authorized users.

Expression and clinical significance of aquaporin-1, vascular endothelial growth factor and microvessel density in gastric cancer

“…[ 28 ] Other studies have shown that with the increase of MVD, the rate of tumor formation, invasion and metastasis also increases. [ 29 , 30 ] The results of this study were consistent with the above reports. The expression intensity of AQP1, VEGF and MVD was not related to tumor size, but was closely related to the differentiation, lymph node metastasis, vascular tumor thrombus and clinical stage of gastric cancer.…”

Serum and tissue expression of neuropilin 1 in precancerous and malignant vocal fold lesions

“…In our study we assumed the non-dysplastic laryngeal lesions as potential control group for comparison with dysplasia and early invasive cancer. Considering that the hypoxic genetic pathways are commonly activated in hyperproliferative lesions and promote angiogenesis through HIF-1α and that NRP-1 expression is significantly increased in hypoxic tumor microenvironment [ 27 ], together with the results of Rzepakowska et al study presenting immunohistochemical staining of laryngeal specimens for HIF-1α and confirming strong expression of the marker throughout all hypertrophic laryngeal lesions with 60% of stained cells in non-dysplastic lesions, 100% in low-grade dysplasia, 53% in high-grade dysplasia and 50% in invasive cancers [ 12 ], it would be recommended to verify the sNRP-1 and tissue NRP-1 expression in samples from patients without any pathological changes of vocal folds. The sampling of healthy vocal fold mucosa carries however a risk of scarring with permanent voice quality deterioration and is therefore avoided.…”

“…Several authors have made the attempt of searching for markers expressed in tissue specimens and/ or in the blood in patients with laryngeal cancer, however no marker has demonstrated a high enough specificity [ 9 – 11 ]. Angiogenesis seems to be an essential process in the progression of non-dysplastic laryngeal lesions into the dysplasia [ 12 ]. The predictive value of angiogenic factors in laryngeal cancer is the subject of contemporary researches with the majority concentrating on the activity of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) axis regulated by transcription factors such as hypoxia inducible factor 1α (HIF-1α) and co-receptors such as vascular endothelial growth factor receptor 1 (VEGFR1) and Neuropilins 1 and 2 (NRP 1, 2).…”

High-Affinity Cu(I)-Chelator with Potential Anti-Tumorigenic Action—A Proof-of-Principle Experimental Study of Human H460 Tumors in the CAM Assay

“…While the fraction of HIF-1α + cells was 18 ± 15% under low-dose conditions, it was 42 ± 11% under high-dose and 31 ± 15% in the control, respectively. According to the categories set up for HIF-1α + cell nuclei reported by Rzepakowska et al [ 48 ], the low-dose PSP-2 results lie in category 1, defined as 1–25%, while the high-dose and control lie in category 2, ranging between 25–50%, respectively.…”