WRAP53β, survivin and p16INK4a expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer

Oncol Rep. 2017 Oct;38(4):2062-2068. doi: 10.3892/or.2017.5898. Epub 2017 Aug 11.

Abstract

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53β, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53β revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53β as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / biosynthesis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy
  • Cisplatin / therapeutic use*
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Female
  • Glottis / drug effects
  • Glottis / pathology*
  • Glottis / radiation effects
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / therapy*
  • Male
  • Middle Aged
  • Molecular Chaperones
  • Neoplasm Staging
  • Predictive Value of Tests
  • Squamous Cell Carcinoma of Head and Neck
  • Survivin
  • Telomerase / biosynthesis*

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Inhibitor of Apoptosis Proteins
  • Molecular Chaperones
  • Survivin
  • Telomerase
  • WRAP53 protein, human
  • Cisplatin