Prognostic impact of combined immunoprofiles in oropharyngeal squamous cell carcinoma patients with respect to AJCC 8th edition

J Oral Pathol Med. 2018 Oct;47(9):864-872. doi: 10.1111/jop.12772. Epub 2018 Aug 25.

Abstract

Objectives: To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed.

Methods: The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed.

Results: The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD44+ and EGFR+ OPSCC displayed worse OS and LRC, and these cases also showed the worst 3-year OS and LRC. Combined analysis of protein expressions identified an association between p16- and EGFR+, p16- and CD44+, EGFR+, and CD44+. Combined immunoprofiles CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ were associated with worst OS and LRC.

Conclusions: Combined immunoprofiles of p16, EGFR, and CD44 might provide valuable prognostic and predictive information for the individual OPSCC patients, especially in terms of response to IMRT and prediction of treatment outcomes. Application of the AJCC 8th edition staging for HPV+ OPSCC proved to improve hazard discrimination and prognostication of OPSCC.

Keywords: EGFR; OPSCC; CD44; combined immunoprofiles; p16.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • ErbB Receptors / analysis
  • Female
  • Humans
  • Hyaluronan Receptors / analysis*
  • Immunohistochemistry*
  • Male
  • Middle Aged
  • Neoplasm Staging / methods*
  • Oropharyngeal Neoplasms / diagnosis*
  • Oropharyngeal Neoplasms / pathology*
  • Prognosis

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Hyaluronan Receptors
  • EGFR protein, human
  • ErbB Receptors