Prognostic significance of HIF-1a, CA-IX, and OPN in T1-T2 laryngeal carcinoma treated with radiotherapy

Laryngoscope. 2013 Sep;123(9):2154-60. doi: 10.1002/lary.23831.

Abstract

Objectives/hypothesis: To examine the prognostic value of hypoxia inducible factor HIF-1a, CA-IX, and OPN on clinical outcome in patients with T1-T2 supraglottic laryngeal squamous cell carcinoma (LSCC) treated with primarily radiotherapy (RT).

Study design: Retrospective cohort study.

Methods: Tumor tissue sections of 60 patients with T1-T2 supraglottic LSCC treated with primarily radiotherapy were assessed immunohistochemically for expression of HIF-1a, CA-IX, and OPN. The relationship of protein expression and classical clinical parameters with clinical outcome was studied, using Cox regression and Kaplan-Meier survival analyses.

Results: Neither HIF-1a nor CA-IX was of prognostic significance toward local control or overall survival in T1-T2 supraglottic LSCC. Cox regression survival analysis showed no relation between HIF-1a or CA-IX expression and local control (HR [hazard ratio] 1.07, CI [95% confidence interval] 0.29-3.87; HR 0.34, CI 0.04-2.58). Furthermore, OPN expression was not associated with local control (HR 1.37, CI 0.45-4.17) and overall survival (HR 0.99, CI 0.44-2.21). Our earlier findings in T1-T2 glottic LSCC (Schrijvers et al., 2008) could not be confirmed.

Conclusion: The absence of prognostic significance for HIF-1a and CA-IX toward local control in supraglottic LSCC, unlike glottic LSCC, suggests that supraglottic LSCC might represent another biological entity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / analysis*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Cohort Studies
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis*
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / mortality*
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Osteopontin / metabolism*
  • Peptide Fragments / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Peptide Fragments
  • osteopontin (1-168), human
  • Osteopontin
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases