Elevated COX-2 expression in cervical carcinoma: reduced cause-specific survival and pelvic control.
The purpose of this study was to correlate the level of cyclooxygenase-2 (COX-2) expression in carcinoma of the cervix with the clinical endpoints: local control, cause-specific survival, and patterns of failure in patients treated with radiotherapy. Formalin-fixed, paraffin-embedded tumor biopsies were stained for COX-2. Clinical factors such as stage, grade, tumor size, pre- and posttreatment hemoglobin level, and radiotherapy dose were also evaluated. Actuarial local control rates and cause-specific survival were determined according to the Kaplan-Meier method. COX-2 distribution staining was the only prognostic factor that was associated with local control and cause-specific survival. High COX-2 distribution staining was associated with decreased local control and decreased cause-specific survival by log rank comparison of Kaplan-Meier survival curves. The 5-year cause-specific survival rates for tumors with low versus high COX-2 distribution values were 90% and 22%, respectively (p = 0.0003). Actuarial pelvic control at 5 years was superior in patients with low COX-2 distribution staining (92%) compared with high staining (42%, p = 0.005). COX-2 staining intensity was found to correlate positively with tumor size (p = 0.02). These findings indicate that increased expression of COX-2 yields reduced pelvic control and cause-specific survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Previously, inhibition of COX-2 has been demonstrated to sensitize tumors to radiation without effect on normal tissue. Taken together, these data may support a novel therapeutic application of COX-2 inhibitors in the treatment of carcinoma of the cervix.
Gaffney
D K
DK
Department of Radiation Oncology, University of Utah, Salt Lake City, 84132, USA.
Holden
J
J
Zempolich
K
K
Murphy
K J
KJ
Dicker
A P
AP
Dodson
M
M
D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009367:Neoplasm Staging; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D017211:Treatment Failure; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases