Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma.

Objectives/hypothesis: To determine the prognostic value of hypoxia-associated markers carbonic anhydrase-9 (CA-9) and hypoxia-inducible factor-1α (HIF-1α) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies.

Study Design: Retrospective cohort study.

Methods: Pretreatment CA-9 and HIF-1α expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3-4 SCCa larynx or hypopharynx treated by (chemo)radiation.

Results: Adverse prognostic factors for locoregional control were T4 classification (P = 0.008), and for disease-specific survival were CA-9 positivity (P = 0.039), T4 classification (P = 0.001), larger tumor volume (P = 0.004), N1-3 classification (P = 0.002), and pretreatment hemoglobin < 13.0 g/dl (P = 0.014). With increasing CA-9 expression, there was a trend to increasing tumor recurrence (P trend = 0.009) and decreasing survival (P trend = 0.002). On multivariate analysis, independent variables were T4 classification (hazard ratio [HR] 13.54, P = 0.01) for locoregional failure, and CA-9 positivity (HR = 8.02, P = 0.042) and higher tumor volume (HR = 3.33, P = 0.007) for disease-specific mortality.

Conclusion: This is the first study to look specifically at T3 and T4 SCCa larynx and hypopharynx for a relationship between hypoxia-associated marker expression and clinical outcome. Pretreatment immunohistochemical CA-9 expression is an adverse prognostic factor for disease-specific survival, indicating that CA-9 expression may confer a more aggressive tumor phenotype.