Top

European Archives of Oto-Rhino-Laryngology

Published in:

Open Access 01-04-2019 | Laryngeal Cancer | Laryngology

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

Authors: Anna Rzepakowska, Michał Żurek, Jakub Grzybowski, Paweł Pihowicz, Barbara Górnicka, Kazimierz Niemczyk, Ewa Osuch-Wójcikiewicz

Published in: European Archives of Oto-Rhino-Laryngology | Issue 4/2019

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.

Available only for authorised users

Gale N, Gnepp DR, Poljak M, Strojan P, Cardesa A, Helliwell T, Šifrer R, Volavšek M, Sandison A, Zidar N (2016) Laryngeal squamous intraepithelial lesions: an updated review on etiology, classification, molecular changes, and treatment. Adv Anat Pathol 23(2):84–91CrossRefPubMed

Trivedi S, Rosen CA, Ferris RL (2016) Current understanding of the tumor microenvironment of laryngeal dysplasia and progression to invasive cancer. Curr Opin Otolaryngol Head Neck Surg 24(2):121–127CrossRefPubMedPubMedCentral

Lionello M, Staffieri A, Marioni G (2012) Potential prognostic and therapeutic role for angiogenesis markers in laryngeal carcinoma. Acta Otolaryngol 132(6):574–582CrossRefPubMed

Karseladze AI (2016) Intraepithelial ischemia is a principal factor promoting cancerization of the covering epithelial tissues. Med Hypotheses 94:154–160CrossRefPubMed

Gale N, Poljak M, Zidar N (2017) 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. Head Neck Pathol 11(1):23–32CrossRefPubMedPubMedCentral

Arens C, Glanz H, Wönckhaus J, Hersemeyer K, Kraft M (2007) Histologic assessment of epithelial thickness in early laryngeal cancer or precursor lesions and its impact on endoscopic imaging. Eur Arch Otorhinolaryngol 264(6):645–649CrossRefPubMed

Dispenza F, De Stefano A, Marchese D, Martines F, Dispenza C (2012) Management of laryngeal precancerous lesions. Auris Nasus Larynx 39:280–283CrossRefPubMed

Gallo A, de Vincentiis M, Della Rocca C, Moi R, Simonelli M, Minni A et al (2001) Evolution of precancerous laryngeal lesion: a clinicopathologic study with long-term follow-up on 259 patients. Head Neck 23:40–47CrossRef

Kojc N, Zidar N, Vodopivec B, Gale N (2005) Expression of CD34, alpha-smooth muscle actin, and transforming growth factor beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx. Hum Pathol 36(1):16–21CrossRefPubMed

10.

Szafarowski T, Sierdzinski J, Szczepanski MJ, Whiteside TL, Ludwig N, Krzeski A (2018) Microvessel density in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 275(7):1845–1851CrossRefPubMedPubMedCentral

11.

Jiang S, Yang Y, Fang M, Li X, Yuan X, Yuan J (2016) Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion. Oncol Lett 12(4):2625–2631CrossRefPubMedPubMedCentral

12.

Konda VJ1, Hart J, Lin S, Tretiakova M, Gordon IO, Campbell L, Kulkarni A, Bissonnette M, Seewald S, Waxman I (2013) Evaluation of microvascular density in Barrett’s associated neoplasia. Mod Pathol 26(1):125–130CrossRefPubMed

13.

Bolzoni Villaret A, Barbieri D, Peretti G et al (2013) Angiogenesis and lymphangiogenesis in early-stage laryngeal carcinoma: prognostic implications. Head Neck 35:1132–1137CrossRefPubMed

14.

Schlüter A, Weller P, Kanaan O, Nel I, Heusgen L, Höing B, Haßkamp P, Zander S, Mandapathil M, Dominas N, Arnolds J, Stuck BA, Lang S, Bankfalvi A, Brandau S (2018) CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma. BMC Cancer 18(1):272. https://doi.org/10.1186/s12885-018-4180-5 CrossRefPubMedPubMedCentral

15.

Pignataro L, Carboni N, Midolo V et al (2001) Clinical relevance of microvessel density in laryngeal squamous cell carcinomas. Int J Cancer 92:666–670CrossRefPubMed

16.

Kwon OJ, Park JJ, Ko GH, Seo JH, Jeong BK, Kang KM, Woo SH, Kim JP, Hwa JS, Carey TE (2015) HIF-1α and CA-IX as predictors of locoregional control for determining the optimal treatment modality for early-stage laryngeal carcinoma. Head Neck 37(4):505–510CrossRefPubMed

17.

Sun S, Pan X, Zhao L, Zhou J, Wang H, Sun Y (2016) The expression and relationship of CD68-tumor-associated macrophages and microvascular density with the prognosis of patients with laryngeal squamous cell carcinoma. Clin Exp Otorhinolaryngol 9(3):270–277CrossRefPubMedPubMedCentral

18.

Popov TM, Dikov T, Goranova TE, Stancheva G, Kaneva RP, Todorov S, Stoyanov O, Rangachev J, Marinov T, Popova DP, Mitev VI, Konov D (2015) Macrophageal infiltration and microvessel density in laryngeal carcinoma: study of 52 cases. Acta Otorhinolaryngol Ital 35(5):321–324PubMedPubMedCentral

19.

Pietruszewska W, Kobos J, Gryczyński M (2003) Microvessel density and endothelial area in assessment of angiogenesis in patients with laryngeal cancer. Otolaryngol Pol 57(1):5–15PubMed

20.

Starska K, Forma E, Jóźwiak P, Bryś M, Lewy-Trenda I, Brzezińska-Błaszczyk E, Krześlak A (2015) 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. Tumour Biol 36(4):2309–2321CrossRefPubMed

21.

Li DW, Dong P, Wang F, Chen XW, Xu CZ, Zhou L (2013) Hypoxia induced multidrug resistance of laryngeal cancer cells via hypoxia-inducible factor-1α. Asian Pac J Cancer Prev 14(8):4853–4858CrossRefPubMed

22.

Gong L, Zhang W, Zhou J, Lu J, Xiong H, Shi X, Chen J (2013) Prognostic value of HIFs expression in head and neck cancer: a systematic review. PLoS One 8(9):e75094CrossRefPubMedPubMedCentral

Title: Microvascular density and hypoxia-inducible factor in intraepithelial vocal fold lesions
Authors: Anna Rzepakowska
Michał Żurek
Jakub Grzybowski
Paweł Pihowicz
Barbara Górnicka
Kazimierz Niemczyk
Ewa Osuch-Wójcikiewicz
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Keywords: Laryngeal Cancer
Laryngeal Cancer
Published in: European Archives of Oto-Rhino-Laryngology / Issue 4/2019
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-019-05355-2

At a glance: The STEP trials

Springer Medicine

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

Abstract

Objective

Materials and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2019

Elective neck treatment during salvage (pharyngo) laryngectomy

Consequences of hearing aid acclimatization on ALLRs and its relationship with perceived benefit and speech perception abilities

An investigation of oxidative stress and coenzyme Q10 levels in patients with head and neck squamous cell carcinomas

Is there a relationship between Onodi cell and optic canal?

Diagnosis and treatment choices of suspected benign paroxysmal positional vertigo: current approach of general practitioners, neurologists, and ENT physicians

Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma