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

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Abstract

Objective

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.

Materials and methods

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.

Results

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).

Conclusion

The 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 material

The online version of this article (10.1007/s00405-019-05355-2) contains supplementary material, which is available to authorized users.

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Most cited references 21

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Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

Mario Poljak, Nina Zidar, Nina Gale (2017)

Chapter 3 “Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space” of the World Health Organization (WHO) Blue Book 2017 “Classification of Head and Neck Tumours” shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial—mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.

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CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma

Anke Schlüter, Patrick Weller, Oliver Kanaan … (2018)

Background Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients. Methods Tissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median

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Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Katarzyna Starska, Ewa Forma, Paweł Jóźwiak … (2014)

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative real-time PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p < 0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p < 0.05). SLC2A3 was related to grade and invasion type (p < 0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p < 0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.

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Author and article information

Contributors

Jakub Grzybowski:

ORCID: http://orcid.org/0000-0001-5549-2266

+48 22 599 16 70 , jgrzybowski@wum.edu.pl

Journal

Journal ID (nlm-ta): Eur Arch Otorhinolaryngol

Journal ID (iso-abbrev): Eur Arch Otorhinolaryngol

Title: European Archives of Oto-Rhino-Laryngology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0937-4477

ISSN (Electronic): 1434-4726

Publication date (Electronic): 6 March 2019

Publication date PMC-release: 6 March 2019

Publication date (Print): 2019

Volume: 276

Issue: 4

Pages: 1117-1125

Affiliations

[1 ]ISNI 0000000113287408, GRID grid.13339.3b, Otolaryngology Department, , Medical University of Warsaw, ; Warsaw, Poland

[2 ]ISNI 0000000113287408, GRID grid.13339.3b, Students Scientific Research Group by Otolaryngology Department, , Medical University of Warsaw, ; Warsaw, Poland

[3 ]ISNI 0000000113287408, GRID grid.13339.3b, Department of Pathology, , Medical University of Warsaw, ; 7, Pawińskiego Str., 02-004 Warsaw, Poland

Author information

Jakub Grzybowski http://orcid.org/0000-0001-5549-2266

Article

Publisher ID: 5355

DOI: 10.1007/s00405-019-05355-2

PMC ID: 6426810

PubMed ID: 30840126

SO-VID: fd3112a9-9c7d-417e-9ba1-4dc6a691110c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 13 October 2018

Date accepted : 20 February 2019

Custom metadata

ScienceOpen disciplines: Otolaryngology

Keywords: intraepithelial lesions,dysplasia,glottic cancer,larynx,microvascular density,hypoxia,angiogenesis

Data availability:

ScienceOpen disciplines: Otolaryngology

Keywords: intraepithelial lesions, dysplasia, glottic cancer, larynx, microvascular density, hypoxia, angiogenesis

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

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Most cited references 21

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

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