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Prognostic Significance of Vascular Endothelial Growth Factor in Squamous Cell Carcinomas of the Tonsil in Relation to Human Papillomavirus Status and Epidermal Growth Factor Receptor

  • Translational Research and Biomarkers
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Abstract

Background

Angiogenesis markers, vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been associated with prognosis in squamous cell carcinomas (SCCs) of the head and neck. Other prognostic variables such as human papillomavirus (HPV) and epidermal growth factor (EGFR) may also be involved in tumour angiogenesis. This study determined relationships between VEGF, MVD, EGFR, HPV, response to radiotherapy and clinical outcome in 85 tonsillar SCCs.

Methods

HPV status was determined by an HPV multiplex real-time polymerase chain reaction (PCR) assay/p16 immunohistochemistry. Expression of VEGF, CD31 (as marker of MVD) and EGFR was assessed by semiquantitative immunohistochemistry.

Results

Strong VEGF expressers were significantly more likely to have higher MVD than were weak expressers. There were no associations between VEGF or MVD and gender, patient age, TNM stage, EGFR expression or HPV status. Tumours with MVD of >15 per high-power field were significantly more likely to be poorly differentiated. There was a significant inverse relationship between EGFR and HPV status. HPV was a strong independent marker of loco-regional recurrence and death. VEGF and EGFR were risk factors for local recurrence and disease-specific death on univariate analysis but the associations weakened after adjustment for HPV. Among patients treated with radiotherapy, VEGF was associated with disease-specific death after adjusting for HPV and TMN stage. High-VEGF-expressing tumours positive for EGFR had a worse prognosis than all other groups combined after adjusting for HPV and TNM stage.

Conclusions

HPV is a stronger prognostic marker than VEGF or EGFR in tonsillar SCCs. VEGF correlates with MVD in these tumours.

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Acknowledgment

We gratefully acknowledge the financial support of the Sydney Head and Neck Cancer Institute. We thank Wei Li, Nham Tran, Luiza Peculis, Cecilia Ng and Elise Jackson for technical support. The HPV MT-PCR assays were performed by Ethel Reyes.

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Authors and Affiliations

  1. The Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Jimin Fei MMed, Deanna Jones BAppSc, Jonathan Clark FRACS, Christopher J. O’Brien FRACS & Barbara Rose PhD

  2. Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan Province, People’s Republic of China

    Jimin Fei MMed

  3. Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Angela Hong FRANZCR

  4. Central Clinical School, University of Sydney, Sydney, NSW, Australia

    Angela Hong FRANZCR

  5. Integrated Cancer Research Group, UNSW Cancer Research Centre, Sydney, NSW, Australia

    Timothy A. Dobbins PhD

  6. Department of Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, Australia

    Deanna Jones BAppSc & Barbara Rose PhD

  7. Discipline of Pathology, School of Medicine, University of Western Sydney, Sydney, NSW, Australia

    C. Soon Lee FRCPA, Christine Loo FRCPA & Mohammad Al-Ghamdi MBBS

  8. Department of Anatomical Pathology, Liverpool Hospital, Sydney, NSW, Australia

    C. Soon Lee FRCPA, Christine Loo FRCPA & Mohammad Al-Ghamdi MBBS

  9. Cancer Pathology, Bosch Institute, University of Sydney, Sydney, NSW, Australia

    C. Soon Lee FRCPA

  10. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    C. Soon Lee FRCPA

  11. Pathwest Laboratory Medicine, QEII Medical Centre, Nedlands, Perth, WA, Australia

    Gerald B. Harnett PhD

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  1. Jimin Fei MMed
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Correspondence to Barbara Rose PhD.

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Fei, J., Hong, A., Dobbins, T.A. et al. Prognostic Significance of Vascular Endothelial Growth Factor in Squamous Cell Carcinomas of the Tonsil in Relation to Human Papillomavirus Status and Epidermal Growth Factor Receptor. Ann Surg Oncol 16, 2908–2917 (2009). https://doi.org/10.1245/s10434-009-0579-1

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  • DOI: https://doi.org/10.1245/s10434-009-0579-1

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