Original Article | Published:

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Modern Pathology volume 31, pages 275287 (2018) | Download Citation


Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.

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We gratefully acknowledge the philanthropic financial support from ICAP, the O’Sullivan family, the Tag family foundation and David Paradice for their generosity and funding assistance. The preliminary results of this study have been presented at the United States and Canadian Academy of pathologists meeting in San Antonio, USA in March 2017 and at the Australia and New Zealand Head and Neck Cancer Society 18th Annual Scientific Meeting in October 2016 Auckland, New Zealand.

Author information


  1. Central Clinical School, The University of Sydney, Sydney, Australia

    • Catherine Zilberg
    • , Matthew Weicai Lee
    • , Bing Yu
    • , Carsten E Palme
    • , Sydney Ch'ng
    • , Tsu-Hui(Hubert) Low
    • , Sandra O'Toole
    • , Jonathan R Clark
    •  & Ruta Gupta
  2. Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, Australia

    • Bing Yu
    •  & Spiridoula Kraitsek
  3. Illawarra and Shoalhaven Local Health District (ISLHD), Wollongong, Australia

    • Bruce Ashford
  4. School of Biological Sciences, University of Wollongong, Wollongong, Australia

    • Bruce Ashford
    •  & Marie Ranson
  5. Illawarra Health and Medical Research Institute (IHMRI), Wollongong, Australia

    • Bruce Ashford
    •  & Marie Ranson
  6. Centre for Oncology Education and Research Translation (CONCERT), Liverpool, Australia

    • Marie Ranson
  7. The Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse, Sydney, Australia

    • Kerwin Shannon
    • , Carsten E Palme
    • , Sydney Ch'ng
    • , Tsu-Hui(Hubert) Low
    •  & Jonathan R Clark
  8. Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, Australia

    • Mark Cowley
  9. Singhealth/Duke-NUS Head and Neck Center, National Cancer Center Singapore (NCCS), Singapore

    • N Gopalakrishna Iyer
  10. St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia

    • Mark Cowley
  11. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia

    • Sandra O'Toole
    •  & Ruta Gupta


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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Ruta Gupta.

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Supplementary Information accompanies the paper on Modern Pathology website (http://www.nature.com/modpathol)