Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 13;12(11):3358.
doi: 10.3390/cancers12113358.

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1-4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Eric Deuss  1   2 , Dorothee Gößwein  2 , Désirée Gül  2 , Stefanie Zimmer  3 , Sebastian Foersch  3 , Claudia S Eger  2 , Ivonne Limburg  2 , Roland H Stauber  2   4 , Julian Künzel  2   5
Affiliations

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1-4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Eric Deuss et al. Cancers (Basel). .

Abstract

This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1-4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1-4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24-5.18) and 2.45 (p = 0.02; 95% CI 1.13-5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment.

Keywords: EGFR; HPV; c-Met; growth factor receptor; immunohistochemistry; oropharyngeal squamous cell cancer OPSCC; p16; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Membranous expression of EGFR; membranous expression of Her2; membranous/cytoplasmatic expression of Her3; membranous/cytoplasmatic/nuclear expression of Her4; and membranous ex-pression of c-Met. Black bar, 250 µm.
Figure 2
Figure 2
Expression distribution of growth factor receptors in relation to the clinical features: (a) EGFR and p16 expression; (b) EGFR expression and T category; (c) Her2 expression and pack years; (d) Her4 expression and tumor site; (e) c-Met and p16 expression; (f) c-Met expression and pack years; (g) c-Met expression and T category; (h) Her4 Expression and tumor stage; and (i) Her4 expression and nodal positivity. (a,c,e,f) Box plots with whiskers showing median, quartiles, maximum and minimum; (b,g) column bar graphs showing mean with standard deviation; (d) column bar graph showing before and after values; and (h,i) interleaved bars comparing absolute values.
Figure 2
Figure 2
Expression distribution of growth factor receptors in relation to the clinical features: (a) EGFR and p16 expression; (b) EGFR expression and T category; (c) Her2 expression and pack years; (d) Her4 expression and tumor site; (e) c-Met and p16 expression; (f) c-Met expression and pack years; (g) c-Met expression and T category; (h) Her4 Expression and tumor stage; and (i) Her4 expression and nodal positivity. (a,c,e,f) Box plots with whiskers showing median, quartiles, maximum and minimum; (b,g) column bar graphs showing mean with standard deviation; (d) column bar graph showing before and after values; and (h,i) interleaved bars comparing absolute values.
Figure 3
Figure 3
(a) Heatmap of growth factor receptor expression in primary tumors sorted by EGFR expression and expression values converted from a 0–300 to a 0–100 scale; and (b) heatmap of growth factor receptor expression in all assessed tumor tissues (primary tumor, local recurrent tumor, lymph node metastasis and distant metastasis) sorted by EGFR expression, expression values converted from a 0–300 to a 0–100 scale.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Beltz A., Gosswein D., Zimmer S., Limburg I., Wunsch D., Gribko A., Deichelbohrer M., Hagemann J., Stauber R.H., Kunzel J. Staging of oropharyngeal squamous cell carcinoma of the head and neck: Prognostic features and power of the 8th edition of the UICC staging manual. Eur. J. Surg. Oncol. 2019;45:1046–1053. doi: 10.1016/j.ejso.2019.02.032. - DOI - PubMed
    1. Chaturvedi A.K., Anderson W.F., Lortet-Tieulent J., Curado M.P., Ferlay J., Franceschi S., Rosenberg P.S., Bray F., Gillison M.L. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J. Clin. Oncol. 2013;31:4550–4559. doi: 10.1200/JCO.2013.50.3870. - DOI - PMC - PubMed
    1. Gillison M.L., Castellsague X., Chaturvedi A., Goodman M.T., Snijders P., Tommasino M., Arbyn M., Franceschi S. Eurogin Roadmap: Comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix. Int. J. Cancer. 2014;134:497–507. doi: 10.1002/ijc.28201. - DOI - PubMed
    1. Mahal B.A., Catalano P.J., Haddad R.I., Hanna G.J., Kass J.I., Schoenfeld J.D., Tishler R.B., Margalit D.N. Incidence and demographic burden of HPV-associated oropharyngeal head and neck cancers in the United States. Cancer Epidemiol. Prev. Biomark. 2019;28:1660–1667. doi: 10.1158/1055-9965.EPI-19-0038. - DOI - PubMed