Synergistic loss of E-cadherin and acquisition of vimentin are characteristic feature of epithelial–mesenchymal transition (EMT) which confers an invasive phenotype of epithelial cancer cells. The aim of the study was to evaluate the prognostic significance of E-cadherin and vimentin expression individually and in combination as a measure of epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Expression of E-cadherin and vimentin through immunohistochemical analysis was examined in 200 patients with surgically resected OSCC. Combined E-cadherin and vimentin expression was evaluated to determine the EMT status. Kaplan–Meier curves and log-rank test were used to compare differences in survival. Cox regression analysis was performed to identify independent prognostic factors. E-cadherin expression was negative in 28 (14%) tumors, and vimentin expression was positive in 87 (43.5%) tumors. Moreover, 99 (49.5%), 87 (43.5%), and 14 (7.5%) tumors exhibited no, partial, and complete EMT, respectively. Both individual protein expression were significant prognostic factors [Negative E-cadherin, hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.04–2.93; positive vimentin, HR = 1.64, 95% CI = 1.12–2.41]. For EMT status, the HR increased with EMT progression [partial EMT, HR = 1.64, 95% CI = 1.09–2.49; complete EMT, HR = 2.88, 95% CI = 1.44–5.79], of which, the complete EMT had higher HR than was individual protein expression. Combined E-cadherin and vimentin expression as a measure of EMT showed a superior prognostic significance compared with individual protein expression.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Age-standardized incidence rate
Oral squamous cell carcinoma
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424
Virani S, Bilheem S, Chansaard W, Chitapanarux I, Daoprasert K, Khuanchana S, Leklob A, Pongnikorn D, Rozek LS, Siriarechakul S, Suwanrungruang K, Tassanasunthornwong S, Vatanasapt P, Sriplung H (2017) National and subnational population-based incidence of cancer in Thailand: assessing cancers with the highest burdens. Cancers 9:108
Pruegsanusak K, Peeravut S, Leelamanit V, Sinkijcharoenchai W, Jongsatitpaiboon J, Phungrassami T, Chuchart K, Thongsuksai P, Pruegsanusak K, Peeravut S, Leelamanit V et al (2012) Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand. Asian Pac J Cancer Prev 13:885–850
Chen TC, Hsu CW, Lou PJ, Ko JY, Yang TL, Chen CN, Chang YL, Wang CP (2013) The clinical predictive factors for subsequent distant metastasis in patients with locoregionally advanced oral squamous cell carcinoma. Oral Oncol 49:367–373
Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142
Scanlon CS, Van Tubergen EA, Inglehart RC, D’Silva NJ (2013) Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res 92:114–121
Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196
Sato R, Semba T, Saya H, Arima Y (2016) Concise review: stem cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem Cells 34:1997–2007
Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, Chen ZQ, Liu XP, Xu ZD (2009) Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res 15:2657–2665
Liu LK, Jiang XY, Zhou XX, Wang DM, Song XL, Jiang HB (2010) Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod Pathol 23:213–224
Fan CC, Wang TY, Cheng YA, Jiang SS, Cheng CW, Lee AY, Kao TY (2013) Expression of E-cadherin, twist, and p53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol 139:1735–1744
Sawant SS, Vaidya MM, Chaukar DA Alam H, Dmello C, Gangadaran P, Kannan S, Kane S, Dange PP, Dey N, Ranganathan K, D'Cruz AK (2014) Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas. Oral Dis 20:453–465
Liu PF, Kang BH, Wu YM, Sun JH, Yen LM, Fu TY, Lin YC, Liou HH, Lin YS, Sie HC, Hsieh IC, Tseng YK, Shu CW, Hsieh YD, Ger LP (2017) Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial-mesenchymal transition-related proteins. PLoS One 12:e0178581
Pyo SW, Hashimoto M, Kim YS, Kim CH, Lee SH, Johnson KR, Wheelock MJ, Park JU (2007) Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome. J Craniomaxillofac Surg 35:1–9
Wolf GT, Winter W, Bellile E, Nguyen A, Donnelly CR, McHugh JB, Thomas D, Amlani L, Rozek L, Lei YL, Head and Neck SPORE Program (2018) Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck. Oral Oncol 87:29–35
Aruga N, Kijima H, Masuda R, Onozawa H, Yoshizawa T, Tanaka M, Inokuchi S, Iwazaki M (2018) Epithelial-mesenchymal transition (EMT) is correlated with patient's prognosis of lung squamous cell carcinoma. Tokai J Exp Clin Med 43:5–13
da Cunha IW, Souza MJ, da Costa WH, Amâncio AM, Fonseca FP, Zequi Sde C, Lopes A, Guimarães GC, Soares F (2016) Epithelial-mesenchymal transition (EMT) phenotype at invasion front of squamous cell carcinoma of the penis influences oncological outcomes. Urol Oncol 34:433.e19–433.e26
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35
Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68:3033–3046
Bánkfalvi A, Krassort M, Buchwalow IB, Végh A, Felszeghy E, Piffkó J (2002) Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression. J Pathol 198:343–351
Mandal M, Myers JN, Lippman SM, Johnson FM, Williams MD, Rayala S, Ohshiro K, Rosenthal DI, Weber RS, Gallick GE, El-Naggar AK (2008) Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features. Cancer 112:2088–2100
Zhou J, Tao D, Xu Q, Gao Z, Tang D (2015) Expression of E-cadherin and vimentin in oral squamous cell carcinoma. Int J Clin Exp Pathol 8:3150–3154
Ukpo OC, Thorstad WL, Zhang Q, Lewis JS Jr (2012) Lack of association of cadherin expression and histopathologic type, metastasis, or patient outcome in oropharyngeal squamous cell carcinoma: a tissue microarray study. Head Neck Pathol 6:38–47
Nijkamp MM, Span PN, Hoogsteen IJ, van der Kogel AJ, Kaanders JH, Bussink J (2011) Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients. Radiother Oncol 99:344–348
Lingen MW, Xiao W, Schmitt A, Jiang B, Pickard R, Kreinbrink P, Perez-Ordonez B, Jordan RC, Gillison ML (2013) Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol 49:1–8
Loeschke S, Ohlmann AK, Bräsen JH, Holst R, Warnke PH (2016) Prognostic value of HMGA2, P16, and HPV in oral squamous cell carcinomas. J Craniomaxillofac Surg 44:1422–1429
Rodríguez-Santamarta T, Rodrigo JP, García-Pedrero JM, Álvarez-Teijeiro S, Ángeles Villaronga M, Suárez-Fernández L, Alvarez-Argüelles ME, Astudillo A (2016) Prevalence of human papillomavirus in oral squamous cell carcinomas in northern Spain. Eur Arch Otorhinolaryngol 273:4549–4559
Wang F, Zhang H, Xue Y, Wen J, Zhou J, Yang X, Wei J (2017) A systematic investigation of the association between HPV and the clinicopathological parameters and prognosis of oral and oropharyngeal squamous cell carcinomas. Cancer Med 6:910–917
Khovidhunkit SO, Buajeeb W, Sanguansin S, Poomsawat S, Weerapradist W (2008) Detection of human papillomavirus in oral squamous cell carcinoma, leukoplakia and lichen planus in Thai patients. Asian Pac J Cancer Prev 9:771–775
This work was supported by funding from the Faculty of Medicine, Prince of Songkla University, Thailand. We would like to thank the cancer registry unit for the use of their registry data.
Conflict of Interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Wangmo, C., Charoen, N., Jantharapattana, K. et al. Epithelial–Mesenchymal Transition Predicts Survival in Oral Squamous Cell Carcinoma. Pathol. Oncol. Res. 26, 1511–1518 (2020). https://doi.org/10.1007/s12253-019-00731-z
- Epithelial–mesenchymal transition
- Oral squamous cell carcinoma