Difference in EGFR expression and mean vascular density in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma.

Alejandra Fernández, Javier Fernández, Maureen Marshall, René Martínez, Sven Niklander, Ziyad S Haidar

Abstract


Objective: To evaluate the expression of the epidermal growth factor receptor (EGFR) and mean vascular density (MVD) in normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and methods: Descriptive case study. Nineteen histological samples diagnosed with NOM, 18 diagnosed with OED, and 19 with OSCC, were analyzed with immunohistochemistry against EGFR and CD31. EGFR expression was evaluated by extent and intensity of its expression in normal, dysplastic and neoplastic epithelium. MVD was determined through the detection of blood vessels by antibodies against CD31. Results: Extension of EGFR expression was highest in OSCC followed by OED and lowest in NOM, resulting in significant different between the degrees of extension (p<0.001). Intensity of EGFR was similar in NOM, OED and OSCC, without differences in its expression (p=0.533). Differences in MVD were found between NOM and OSCC groups (p<0.01), and between OED and OSCC groups (p<0.01), with no differences between NOM and OED groups (p=0.91). MVD was 21.17 ± 4.98 in NOM, 23.40 ± 5.77 in OED and 33.92 ± 8.39 in OSCC. Conclusion: EGFR is expressed in normal, dysplastic or neoplastic oral epithelium. However, the extent of its expression is greater as malignancy increases. MVD varies according to the diagnosis.


Keywords


Oral cavity; mouth neoplasms; epidermal growth factor receptor; pathologic angiogenesis.

References


Fernández A, Córdova P, Badenier O, Esguep A. Epidemiological characterization of oral cancer. Literature review. J Oral Res. 2015;4(2):137–45.

Irimie AI, Braicu C, Cojocneanu-Petric R, Berindan-Neagoe I, Campian RS. Novel technologies for oral squamous carcinoma biomarkers in diagnostics and prognostics. Acta Odontol Scand. 2015;73(3):161–8.

Scully C. Challenges in predicting which oral mucosal potentially malignant disease will progress to neoplasia. Oral Dis. 2014;20(1):1–5.

Veeravarmal V, Austin RD, Siddavaram N, Thiruneelakandan S, Nassar MH. Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma. J Oral Maxillofac Pathol. 2016;20(3):445–52.

Pitiyage G, Tilakaratne WM, Tavassoli M, Warnakulasuriya S. Molecular markers in oral epithelial dysplasia: review. J Oral Pathol Med. 2009;38(10):737–52.

Rössle M, Weber CS, Züllig L, Graf N, Jochum W, Stöckli SJ, Moch H, Huber GF. EGFR expression and copy number changes in low T-stage oral squamous cell carcinomas. Histopathology. 2013;63(2):271–8.

Christensen ME, Therkildsen MH, Hansen BL, Albeck H, Hansen GN, Bretlau P. Epidermal growth factor receptor expression on oral mucosa dysplastic epithelia and squamous cell carcinomas. Eur Arch Otorhinolaryngol. 1992;249(5):243–7.

Bruno A, Pagani A, Pulze L, Albini A, Dallaglio K, Noonan DM, Mortara L. Orchestration of angiogenesis by immune cells. Front Oncol. 2014;4:131.

Shivamallappa SM, Venkatraman NT, Shreedhar B, Mohanty L, Shenoy S. Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study. Int J Oral Sci. 2011;3(4):216–24.

Pujari RK, Vanaki SS, Puranik RS, Desai RS, Motupalli N, Halawar S. Histomorphometric analysis of vascularity in normal buccal mucosa, leukoplakia, and squamous cell carcinoma of buccal mucosa. J Oral Maxillofac Pathol. 2013;17(3):334–9.

Ries J, Vairaktaris E, Agaimy A, Bechtold M, Gorecki P, Neukam FW, Nkenke E. The relevance of EGFR overexpression for the prediction of the malignant transformation of oral leukoplakia. Oncol Rep. 2013;30(3):1149–56.

Sarkis SA, Abdullah BH, Abdul Majeed BA, Talabani NG. Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. Head Neck Oncol. 2010;2:13.

Cheng SH, Liu JM, Liu QY, Luo DY, Liao BH, Li H, Wang KJ. Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis. Int J Clin Exp Pathol. 2014;7(9):5855–63.

Krishnan L, Karpagaselvi K, Kumarswamy J, Sudheendra US, Santosh KV, Patil A. Inter- and intra-observer variability in three grading systems for oral epithelial dysplasia. J Oral Maxillofac Pathol. 2016;20(2):261–8.

Geetha KM, Leeky M, Narayan TV, Sadhana S, Saleha J. Grading of oral epithelial dysplasia: Points to ponder. J Oral Maxillofac Pathol. 2015;19(2):198–204.

Shirako Y, Taya Y, Sato K, Chiba T, Imai K, Shimazu Y, Aoba T, Soeno Y. Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma cells in tongue and nodal metastatic lesions in a xenograft mouse model. J Oral Pathol Med. 2015;44(9):656–68.

Abdulmajeed AA, Farah CS. Can immunohistochemistry serve as an alternative to subjective histopathological diagnosis of oral epithelial dysplasia? Biomark Cancer. 2013;5:49–60.

Noda Y, Kishino M, Sato S, Hirose K, Sakai M, Fukuda Y, Murakami S, Toyosawa S. Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma. J Clin Pathol. 2017;70(2):126–133.

Chrun ED, Modolo F, Vieira DS, Borges ÁL, Castro RG, Daniel FI. Immunoexpression of HDAC1, HDAC2 and HAT1 in actinic cheilitis and lip squamous cell carcinoma. Oral Dis. 2017:[Epub ahead of print].

Laimer K, Spizzo G, Gastl G, Obrist P, Brunhuber T, Fong D, Barbieri V, Jank S, Doppler W, Rasse M, Norer B. High EGFR expression predicts poor prognosis in patients with squamous cell carcinoma of the oral cavity and oropharynx: a TMA-based immunohistochemical analysis. Oral Oncol. 2007;43(2):193–9.

Ziebart T, Blatt S, Günther C, Völxen N, Pabst A, Sagheb K, Kühl S, Lambrecht T. Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization? Clin Oral Investig. 2016;20(8):2293–300.

Goodson ML, Sloan P, Robinson CM, Cocks K, Thomson PJ. Oral precursor lesions and malignant transformation--who, where, what, and when? Br J Oral Maxillofac Surg. 2015;53(9):831–5.

Niu LX, Feng ZE, Wang DC, Zhang JY, Sun ZP, Guo CB. Prognostic factors in mandibular gingival squamous cell carcinoma: A 10-year retrospective study. Int J Oral Maxillofac Surg. 2017;46(2):137–43.

Matsushita Y, Yanamoto S, Takahashi H, Yamada S, Naruse T, Sakamoto Y, Ikeda H, Shiraishi T, Fujita S, Ikeda T, Asahina I, Umeda M. A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma. Int J Oral Maxillofac Surg. 2015;44(5):543–8.

Narayan TV, Shilpashree S. Meta-analysis on clinicopathologic risk factors of leukoplakias undergoing malignant transformation. J Oral Maxillofac Pathol. 2016;20(3):354–61.

Bijina BR, Ahmed J, Shenoy N, Ongole R, Shenoy S, Baliga S. Detection of human papilloma virus in potentially malignant and malignant lesions of the oral cavity and a study of associated risk factors. South Asian J Cancer. 2016;5(4):179–81.

Dholam KP, Chouksey GC. Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18-45 years: A case-control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history. Indian J Cancer. 2016;53(2):244–51.

Rajeswari MR, Saraswathi TR. Expression of epithelial growth factor receptor in oral epithelial dysplastic lesions. J Oral Maxillofac Pathol. 2012;16(2):183–8.

Ribeiro DC, Gleber-Netto FO, Sousa SF, Bernardes VD, Guimarães-Abreu MH, Aguiar MC. Immunohistochemical expression of EGFR in oral leukoplakia: association with clinicopathological features and cellular proliferation. Med Oral Patol Oral Cir Bucal. 2012;17(5):e739–44.

Dragomir LP, Mărgăritescu C, Florescu A, Olimid AD, Dragomir M, Popescu MR. The immunoexpression of EGFR and Her2/neu in oral squamous carcinoma. Rom J Morphol Embryol. 2012;53(3):597–601.

Yadav L, Puri N, Rastogi V, Satpute P, Sharma V. Tumour Angiogenesis and Angiogenic Inhibitors: A Review. J Clin Diagn Res. 2015;9(6):XE01–5.

Sathyakumar M, Sriram G, Saraswathi T, Sivapathasundharam B. Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia. J Oral Maxillofac Pathol. 2012;16(3):343–8.

Basnaker M, Sr S, Bnvs S. Expression of Endoglin (CD-105) and Microvessel Density in Oral Dysplasia and Squamous Cell Carcinoma. J Clin Diagn Res. 2014;8(9):ZC91–4.

Xiao H, Tong R, Ding CH, Lv Z, Du CH, Peng CH, Cheng S, Xie H, Zhou L, Wu J, Zheng S. γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition. Oncotarget. 2015;6(4):2180–92.


Full Text: PDF

Refbacks

  • There are currently no refbacks.




Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Corresponding: Facultad de Odontología, Universidad de Concepción, Chile. Roosevelt 1550, Concepción, Chile. Phone +56-41-2204232 - Fax +56-41-2243311- Mailbox 160-C, Concepción, Chile. E-mail journal@joralres.com.