High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy.
OBJECTIVE
The cyclooxygenase (COX)-2 enzyme has been shown to have an important role in carcinogenesis and apoptosis in various types of cancer. The purpose of this study was to evaluate the relationship between local recurrence or distant metastasis and COX-2 expression and apoptosis in cervical cancer patients treated with radical radiotherapy (RT).


METHODS
Twenty-two patients who were diagnosed with cervical cancer were enrolled in this study. All patients were treated with radical RT (external beam RT plus brachytherapy) at Seoul National University Hospital. The formalin-fixed, paraffin-embedded tissues of 11 patients who developed local recurrence (n = 3) or distant metastasis (n = 8) were compared with those of other patients who were disease free. Prognostic factors, including tumor size, lymph node metastatic status, and stage, were well balanced between the two groups. COX-2 expression was determined immunohistochemically, and apoptosis was assessed using in situ DNA nick end labeling (TUNEL)-based methods.


RESULTS
COX-2 expression was stronger in the local recurrence and distant metastasis patients than in those free of disease. COX-2 expression was shown to have a statistically significant influence on treatment failure by the Mann-Whitney U test (p = 0.015) and the Mantel-Haenszel chi-square test (p = 0.015), but its distribution did not correlate with apoptosis. Among the clinicopathologic factors, including stage, lymph node metastatic status, and tumor size, lymph node metastatic status was found to closely correlate with COX-2 expression by the Mann-Whitney U test (p = 0.045) and Mantel-Haenszel chi-square test (p = 0.065).


CONCLUSIONS
COX-2 is believed to be one of the important factors associated with lymph node involvement and treatment failure. Our results suggest that inhibiting COX-2 may decrease treatment failure in cervical cancer treated with RT, and that COX-2 inhibitor administration may play an adjuvant role in cervical cancer treatment.
Kim
Hak Jae
HJ
Department of Therapeutic Radiology, Seoul National University College of Medicine, Seoul, South Korea.
Wu
Hong Gyun
HG
Park
In Ae
IA
Ha
Sung Whan
SW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D008207:Lymphatic Metastasis; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D015996:Survival Rate; 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