Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy.
OBJECTIVE
The purpose of this study was to examine the relationship between overall survival and prognostic factors in carcinoma of the cervix treated with radiation therapy. A clinicopathologic study was performed on 24 patients.


METHODS
Formalin-fixed, paraffin-embedded tumor biopsies were stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53. Clinical factors such as stage, grade, tumor size, pre- and post-treatment hemoglobin level, and radiotherapy dose were also evaluated.


RESULTS
Median follow-up was 75 months for living patients. The only immunohistochemical or clinical factor that was associated with improved survival was decreased COX-2 distribution staining. High COX-2 distribution staining was associated with decreased overall survival (p = 0.021) and decreased disease-free survival (p = 0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall survival rates for tumors with low vs. high COX-2 distribution values were 75% and 35%, respectively. COX-2 staining intensity was found to correlate positively with tumor size (p = 0.022).


CONCLUSIONS
These findings indicate that increased expression of COX-2 portends a diminished survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early-response gene involved in angiogenesis and inducible by different stimuli, these data may indicate opportunity to intervene with specific inhibitors of COX-2 in carcinoma of the cervix.
Gaffney
D K
DK
Department of Radiation Oncology, University of Utah, Salt Lake City, UT 84132, USA. david.k.gaffney@hsc.utah.edu
Holden
J
J
Davis
M
M
Zempolich
K
K
Murphy
K J
KJ
Dodson
M
M
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality* / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality* / Q000532:radiotherapy; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000532:radiotherapy
D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases