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Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression

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Abstract

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2–173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as “homogeneous” or “heterogeneous.” We found that patients showing an “heterogeneous” EGFR expression distribution had worse OS and DFS compared to the “homogeneous” group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

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References

  1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.

    Article  PubMed  Google Scholar 

  2. Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century a period analysis. Oncologist. 2010;15(9):994–1001.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bonner JA, Harari PM, Giralt J, Cohen RB, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  4. Budach W, Hehr T, Budach V, et al. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer. 2006;31(6):28.

    Article  Google Scholar 

  5. Yewale C, Baradia D, Vhora I, et al. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34(34):8690–707.

    Article  CAS  PubMed  Google Scholar 

  6. Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5(7):516–25.

    Article  CAS  PubMed  Google Scholar 

  7. Pedicini P, Nappi A, Strigari L, et al. Correlation between EGFr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma. Radiat Oncol. 2012;24(7):143.

    Article  Google Scholar 

  8. Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14.

    Article  PubMed  Google Scholar 

  9. Akhter M, Hossain S, Rahman QB, Molla MR. A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis. J Oral Maxillofac Pathol. 2011;15(2):168–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ansarin M, Santoro L, Cattaneo A, et al. Laser surgery for early glottic cancer: impact of margin status on local control and organ preservation. Arch Otolaryngol Head Neck Surg. 2009;135(4):385–90.

    Article  PubMed  Google Scholar 

  11. NCCN reference. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck_blocks.pdf.

  12. Burandt E, Schreiber M, Stein A, et al. Continuous tissue microarray based identification of cancers with homogeneous target expression for successful targeted therapy in clinical routine practice. Genes Chromosom Cancer. 2014;53(3):228–39.

    Article  CAS  PubMed  Google Scholar 

  13. Bussink J, Kaanders JH, van der Kogel AJ. Microenvironmental transformations by VEGF- and EGF-receptor inhibition and potential implications for responsiveness to radiotherapy. Radiother Oncol. 2007;82(1):10–7.

    Article  CAS  PubMed  Google Scholar 

  14. Hendriksen EM, Span PN, Schuuring J, et al. Angiogenesis, hypoxia and VEGF expression during tumour growth in a human xenograft tumour model. Microvasc Res. 2009;77(2):96–103.

    Article  CAS  PubMed  Google Scholar 

  15. Nijkamp MM, Span PN, Bussink J, Kaanders JH. Interaction of EGFR with the tumour microenvironment: implications for radiation treatment. Radiother Oncol. 2013;108(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  16. Sheridan MT, O’Dwyer T, Seymour CB, Mothersill CE. Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck. Radiat Oncol Investig. 1997;5(4):180–6.

    Article  CAS  PubMed  Google Scholar 

  17. Bossi P, Resteghini C, Paielli N, et al. Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget. 2016;7(45):74362–79.

    PubMed  PubMed Central  Google Scholar 

  18. Bentzen SM, Atasoy BM, Daley FM, et al. Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial. J Clin Oncol. 2005;23(24):5560–7.

    Article  CAS  PubMed  Google Scholar 

  19. Keren S, Shoude Z, Lu Z, Beibei Y. Role of EGFR as a prognostic factor for survival in head and neck cancer: a meta-analysis. Tumour Biol. 2014;35(3):2285–95.

    Article  CAS  PubMed  Google Scholar 

  20. Kearsley JH, Furlong KL, Cooke RA, Waters MJ. An immune-histochemical assessment of cellular proliferation markers in head and neck squamous cell cancers. Br J Cancer. 1990;61(6):821–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Saba NF, Wong SJ. Dual epidermal growth factor receptor and human epidermal growth factor receptor 2 inhibition in squamous cell carcinoma of the head and neck; Is the jury still out? J Clin Oncol. 2016;34(17):2072–3.

    Article  PubMed  Google Scholar 

  22. Laimer K, Spizzo G, Gastl G, et al. 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):193–8.

    Article  CAS  PubMed  Google Scholar 

  23. Psyrri A, Yu Z, Weinberger PM, et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res. 2005;11(16):5856–62.

    Article  CAS  PubMed  Google Scholar 

  24. Wheeler S, Siwak DR, Chai R, et al. Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. Clin Cancer Res. 2012;18(8):2278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gröbe A, Eichhorn W, Fraederich M, et al. Immunohistochemical and FISH analysis of EGFR and its prognostic value in patients with oral squamous cell carcinoma. J Oral Pathol Med. 2014;43(3):205–10.

    Article  PubMed  Google Scholar 

  26. Eriksen JG, Steiniche T, Askaa J, et al. The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2004;58(2):561–6.

    Article  CAS  PubMed  Google Scholar 

  27. Maiorano E, Favia G, Maisonneuve P, Viale G. Prognostic implications of epidermal growth factor receptor immunoreactivity in squamous cell carcinoma of the oral mucosa. J Pathol. 1998;185(2):167–74.

    Article  CAS  PubMed  Google Scholar 

  28. Goldstein NS, Armin M. Epidermal growth factor receptor immunohistochemical reactivity in patients with American joint committee on cancer stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer. 2001;92(5):1331–46.

    Article  CAS  PubMed  Google Scholar 

  29. Eriksen JG, Steiniche T, Overgaard J. Danish head and neck cancer study group (DAHANCA). The role of epidermal growth factor receptor and E-cadherin for the outcome of reduction in the overall treatment time of radiotherapy of supraglottic larynx squamous cell carcinoma. Acta Oncol. 2005;44(1):50–8.

    Article  CAS  PubMed  Google Scholar 

  30. Eriksen JG, Steiniche T, Askaa J, Alsner J, Overgaard J. The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2004;58(2):561–6.

    Article  CAS  PubMed  Google Scholar 

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Funding

The study was partially supported by Merck Serono SpA that provided all the supplies used for the immunohistochemical assay of our samples.

Author information

Author notes

  1. Daniela Alterio and Giulia Marvaso have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiotherapy, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy

    Daniela Alterio, Giulia Marvaso, Annamaria Ferrari, Cristiana Fodor, Antonio Laudati & Barbara A. Jereczek-Fossa

  2. Department of Pathology, European Institute of Oncology, Milan, Italy

    Fausto Maffini & Daniela Lepanto

  3. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

    Sara Gandini

  4. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    Susanna Chiocca

  5. Department of Radiology, European Institute of Oncology, Milan, Italy

    Lorenzo Preda

  6. Medical Oncology Division of Urogenital and Head and Neck Tumours, European Institute of Oncology, Milan, Italy

    Maria Cossu Rocca

  7. Department of Head and Neck Surgery, European Institute of Oncology, Milan, Italy

    Gioacchino Giugliano & Mohssen Ansarin

  8. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Stefania Volpe, Samantha Dicuonzo & Barbara A. Jereczek-Fossa

Authors
  1. Daniela Alterio
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  2. Giulia Marvaso
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  4. Sara Gandini
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  7. Lorenzo Preda
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  11. Stefania Volpe
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  15. Mohssen Ansarin
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  16. Barbara A. Jereczek-Fossa
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Corresponding author

Correspondence to Daniela Alterio.

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Conflict of interest

None.

Ethical approval

The study was a part of curative radiotherapy research for patients with head and neck cancer notified and approved by the Ethical Committee of the European Institute of Oncology, Milan, Italy (notification IEO N94/11-2nd/May/2011).

Informed consent

All the patients involved in this study signed an informed consent.

Additional information

Mohssen Ansarin and Barbara A. Jereczek-Fossa shared co-last-authorship.

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Alterio, D., Marvaso, G., Maffini, F. et al. Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression. Med Oncol 34, 107 (2017). https://doi.org/10.1007/s12032-017-0965-7

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  • DOI: https://doi.org/10.1007/s12032-017-0965-7

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