Tissue microarray analysis reveals prognostic significance of COX-2 expression for local relapse in T1-2N0 larynx cancer treated with primary radiation therapy

Laryngoscope. 2004 Nov;114(11):2001-8. doi: 10.1097/01.mlg.0000147936.67379.e7.

Abstract

Objective: The purpose of this analysis is to determine whether a significant correlation exists between cyclooxygenase-2 (COX-2) expression and local relapse in a large cohort of patients with T1 to 2N0 laryngeal cancer treated with primary radiation therapy.

Methods and materials: Clinical and molecular analyses were conducted on 123 patients with biopsy-proven T1 to 2N0 laryngeal cancer. Clinical prognostic factors included pretreatment hemoglobin, age, sex, race, T stage, tumor subsite, beam energy, biologically equivalent dose, therapy duration, and treatment date. Molecular prognostic factors included COX-2, p53, and Ki-67 expression. Expression levels were determined by immunohistochemistry on paraffin-embedded tissues arrayed on tissue microarrays. Multivariate analysis was done with the Cox proportional hazards model.

Results: Thirty-two patients have locally relapsed, for an actuarial 5-year local relapse-free rate of 70.4%. On multivariate analysis, positive COX-2 expression predicted local relapse after radiation therapy. The relative risk (RR) for local relapse with COX-2 positivity was 2.57 (95% CI, 1.21-5.47; P = .01). Other prognostic factors for local relapse included negative Ki-67 expression (RR = 5.72; 95% CI, 2.04-16.1; P < .001), T2 stage (RR = 2.98; 95% CI, 1.39-6.38; P = .005), and therapy duration greater than 43 days (RR = 6.04; 95% CI, 1.37-26.7; P = .02).

Conclusions: Positive COX-2 expression predicts for local relapse in T1 to 2N0 larynx cancer in a multivariate model. This relationship may have potential therapeutic implications regarding the use of COX-2 inhibitors during radiation therapy for optimal outcome.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cyclooxygenase 2
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / biosynthesis*
  • Laryngeal Neoplasms / enzymology*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / radiotherapy*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Survival Rate

Substances

  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases