Tissue microarray analysis reveals prognostic significance of COX-2 expression for local relapse in T1-2N0 larynx cancer treated with primary radiation therapy.
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
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.
Cho
Edward I
EI
Departments of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA.
Kowalski
Diane P
DP
Sasaki
Clarence T
CT
Haffty
Bruce G
BG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D051546:Cyclooxygenase 2; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000401:mortality; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D015996:Survival Rate
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases