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Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study

  • Authors:
    • Matthias Kappler
    • Kevin Dauter
    • Waldemar Reich
    • Daniel Bethmann
    • Michael Schwabe
    • Swetlana Rot
    • Claudia Wickenhauser
    • Bilal Al‑Nawas
    • Alexander W. Eckert
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle‑Wittenberg, D‑06120 Halle (Saale), Germany, Institute of Pathology, Martin Luther University Halle‑Wittenberg, D‑06110 Halle (Saale), Germany, DRK Kliniken Berlin Westend, D‑14050 Berlin, Germany
    Copyright: © Kappler et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 88
    |
    Published online on: October 21, 2020
       https://doi.org/10.3892/mco.2020.2158
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Abstract

In various tumors, epidermal growth factor‑receptor (EGFR) serves a role in tumorigenesis and has an impact on survival. Usually the EGF‑receptor is located on the surface of the cell membrane and is involved in various signaling pathways. The dimerization of EGFR with other ErbB family proteins, such as HER2, is important for the tumor progression. Nevertheless, a second EGFR‑associated signaling pathway appears to be important for tumor cells, which is cytoplasmic/nuclear EGFR. The present study examined the influence of membranous or cytoplasmic localized EGFR on the prognosis of patients with oral squamous cell carcinoma (OSCC). Slides from 45 OSCC tumor samples were stained against EGFR using immunohistochemistry and analysed by the Remmele score system. The association with histopathological parameters and survival data was analyzed. Cytoplasmatic EGFR localization was identified as an independent predictive biomarker for overall survival in the examined OSCC cohort according to multivariate Cox regression analysis. Positive cytoplasmatic EGFR staining was correlated with a higher risk of early death (RR=3.0; P=0.035), while membranous EGFR localization did not affect patient survival. To the best of our knowledge, the present study is the first study to demonstrate that cytoplasmatic‑localized EGFR is an independent prognostic biomarker for the overall survival of patients with OSCC.
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1 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015.PubMed/NCBI View Article : Google Scholar

2 

Eckert AW, Wickenhauser C, Salins PC, Kappler M, Bukur J and Seliger B: Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma. J Transl Med. 14(85)2016.PubMed/NCBI View Article : Google Scholar

3 

Lo HW and Hung MC: Nuclear EGFR signalling network in cancers: Linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer. 94:184–188. 2006.PubMed/NCBI View Article : Google Scholar

4 

Yarden Y: Grundlagen der Signaltransduktion. Onkologie. 28 (Suppl 4):S14–S17. 2005.(In German). PubMed/NCBI View Article : Google Scholar

5 

Christensen A, Kiss K, Lelkaitis G, Juhl K, Persson M, Charabi BW, Mortensen J, Forman JL, Sørensen AL, Jensen DH, et al: Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): Tumor expression patterns and prognostic value in oral cancer. BMC Cancer. 17(572)2017.PubMed/NCBI View Article : Google Scholar

6 

Bossi P, Resteghini C, Paielli N, Licitra L, Pilotti S and Perrone F: Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget. 7:74362–74379. 2016.PubMed/NCBI View Article : Google Scholar

7 

Søland TM and Brusevold IJ: Prognostic molecular markers in cancer-quo vadis? Histopathology. 63:297–308. 2013.PubMed/NCBI View Article : Google Scholar

8 

Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia W, Wei Y, Bartholomeusz G, Shih JY and Hung MC: Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell. 7:575–589. 2005.PubMed/NCBI View Article : Google Scholar

9 

Marti U, Burwen SJ, Wells A, Barker ME, Huling S, Feren AM and Jones AL: Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology. 13:15–20. 1991.PubMed/NCBI

10 

Lo HW, Xia W, Wei Y, Ali-Seyed M, Huang SF and Hung MC: Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res. 65:338–348. 2005.PubMed/NCBI

11 

Taguchi T: Nuclear translocation of epidermal growth factor receptor and its relation to clinicopathological factors in oral squamous cell carcinomas. Kokubyo Gakkai Zasshi. 81:45–52. 2014.(In Japanese). PubMed/NCBI

12 

Maramotti S, Paci M, Manzotti G, Rapicetta C, Gugnoni M, Galeone C, Cesario A and Lococo F: Soluble epidermal growth factor receptors (sEGFRs) in cancer: Biological aspects and clinical relevance. Int J Mol Sci. 17(593)2016.PubMed/NCBI View Article : Google Scholar

13 

Weinholdt C, Wichmann H, Kotrba J, Ardell DH, Kappler M, Eckert AW, Vordermark D and Grosse I: Prediction of regulatory targets of alternative isoforms of the epidermal growth factor receptor in a glioblastoma cell line. BMC Bioinformatics. 20(434)2019.PubMed/NCBI View Article : Google Scholar

14 

Eckert AW, Lautner MH, Schütze A, Taubert H, Schubert J and Bilkenroth U: Coexpression of hypoxia-inducible factor-1α and glucose transporter-1 is associated with poor prognosis in oral squamous cell carcinoma patients. Histopathology. 58:1136–1147. 2011.PubMed/NCBI View Article : Google Scholar

15 

Eckert AW, Schutze A, Lautner MH, Taubert H, Schubert J and Bilkenroth U: HIF-1alpha is a prognostic marker in oral squamous cell carcinomas. Int J Biol Markers. 25:87–92. 2010.PubMed/NCBI

16 

Wichmann H, Güttler A, Bache M, Taubert H, Rot S, Kessler J, Eckert AW, Kappler M and Vordermark D: Targeting of EGFR and HER2 with therapeutic antibodies and siRNA: A comparative study in glioblastoma cells. Strahlenther Onkol. 191:180–191. 2015.PubMed/NCBI View Article : Google Scholar

17 

Remmele W and Stegner HE: Vorschlag zur einheitlichen definition eines immunreaktiven score (IRS) für den immunhistochemischen ostrogenrezeptor-nachweis (ER-ICA) im mammakarzinomgewebe. Pathologe. 8:138–140. 1987.

18 

Kimura I, Kitahara H, Ooi K, Kato K, Noguchi N, Yoshizawa K, Nakamura H and Kawashiri S: Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition. Oncol Lett. 11:201–207. 2016.PubMed/NCBI View Article : Google Scholar

19 

Rot S, Taubert H, Bache M, Greither T, Würl P, Holzhausen HJ, Eckert AW, Vordermark D and Kappler M: Low HIF-1α and low EGFR mRNA expression significantly associate with poor survival in soft tissue sarcoma patients; the proteins react differently. Int J Mol Sci. 19(3842)2018.PubMed/NCBI View Article : Google Scholar

20 

Greither T, Koser F, Holzhausen HJ, Güttler A, Würl P, Kappler M, Wach S and Taubert H: MiR-155-5p and MiR-203a-3p are prognostic factors in soft tissue sarcoma. Cancers (Basel). 12(2254)2020.PubMed/NCBI View Article : Google Scholar

21 

Sigismund S, Avanzato D and Lanzetti L: Emerging functions of the EGFR in cancer. Mol Oncol. 12:3–20. 2018.PubMed/NCBI View Article : Google Scholar

22 

Ryott M, Wangsa D, Heselmeyer-Haddad K, Lindholm J, Elmberger G, Auer G, Avall Lundqvist E, Ried T and Munck-Wikland E: EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma. Eur J Cancer. 45:1700–1708. 2009.PubMed/NCBI View Article : Google Scholar

23 

Diniz-Freitas M, García-Caballero T, Antúnez-López J, Gándara-Rey JM and García-García A: Pharmacodiagnostic evaluation of EGFR expression in oral squamous cell carcinoma. Oral Dis. 13:285–290. 2007.PubMed/NCBI View Article : Google Scholar

24 

Shah NG, Trivedi TI, Tankshali RA, Goswami JV, Jetly DH, Shukla SN, Shah PM and Verma RJ: Prognostic significance of molecular markers in oral squamous cell carcinoma: A multivariate analysis. Head Neck. 31:1544–1556. 2009.PubMed/NCBI View Article : Google Scholar

25 

Monteiro LS, Diniz-Freitas M, Garcia-Caballero T, Warnakulasuriya S, Forteza J and Fraga M: Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma. J Oral Pathol Med. 41:559–567. 2012.PubMed/NCBI View Article : Google Scholar

26 

Huang SF, Cheng SD, Chien HT, Liao CT, Chen IH, Wang HM, Chuang WY, Wang CY and Hsieh LL: Relationship between epidermal growth factor receptor gene copy number and protein expression in oral cavity squamous cell carcinoma. Oral Oncol. 48:67–72. 2012.PubMed/NCBI View Article : Google Scholar

27 

Maiorano E, Favia G, Maisonneuve P and Viale G: Prognostic implications of epidermal growth factor receptor immunoreactivity in squamous cell carcinoma of the oral mucosa. J Pathol. 185:167–174. 1998.PubMed/NCBI View Article : Google Scholar

28 

Yang CC, Lin LC, Lin YW, Tian YF, Lin CY, Sheu MJ, Li CF and Tai MH: Higher nuclear EGFR expression is a better predictor of survival in rectal cancer patients following neoadjuvant chemoradiotherapy than cytoplasmic EGFR expression. Oncol Lett. 17:1551–1558. 2019.PubMed/NCBI View Article : Google Scholar

29 

Lo HW, Hsu SC and Hung MC: EGFR signaling pathway in breast cancers: From traditional signal transduction to direct nuclear translocalization. Breast Cancer Res Treat. 95:211–218. 2006.PubMed/NCBI View Article : Google Scholar

30 

Takei J, Kaneko MK, Ohishi T, Kawada M, Harada H and Kato Y: A novel anti-EGFR monoclonal antibody (EMab-17) exerts antitumor activity against oral squamous cell carcinomas via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Oncol Lett. 19:2809–2816. 2020.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Kappler M, Dauter K, Reich W, Bethmann D, Schwabe M, Rot S, Wickenhauser C, Al‑Nawas B and Eckert AW: Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study. Mol Clin Oncol 13: 88, 2020.
APA
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S. ... Eckert, A.W. (2020). Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study. Molecular and Clinical Oncology, 13, 88. https://doi.org/10.3892/mco.2020.2158
MLA
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S., Wickenhauser, C., Al‑Nawas, B., Eckert, A. W."Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study". Molecular and Clinical Oncology 13.6 (2020): 88.
Chicago
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S., Wickenhauser, C., Al‑Nawas, B., Eckert, A. W."Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study". Molecular and Clinical Oncology 13, no. 6 (2020): 88. https://doi.org/10.3892/mco.2020.2158
Copy and paste a formatted citation
x
Spandidos Publications style
Kappler M, Dauter K, Reich W, Bethmann D, Schwabe M, Rot S, Wickenhauser C, Al‑Nawas B and Eckert AW: Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study. Mol Clin Oncol 13: 88, 2020.
APA
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S. ... Eckert, A.W. (2020). Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study. Molecular and Clinical Oncology, 13, 88. https://doi.org/10.3892/mco.2020.2158
MLA
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S., Wickenhauser, C., Al‑Nawas, B., Eckert, A. W."Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study". Molecular and Clinical Oncology 13.6 (2020): 88.
Chicago
Kappler, M., Dauter, K., Reich, W., Bethmann, D., Schwabe, M., Rot, S., Wickenhauser, C., Al‑Nawas, B., Eckert, A. W."Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study". Molecular and Clinical Oncology 13, no. 6 (2020): 88. https://doi.org/10.3892/mco.2020.2158
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