Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy.
BACKGROUND
The objective of this study was to determine whether cyclooxygenase-2 (COX-2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy.


METHODS
Seventy-five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX-2 level in an immunohistochemical study: the COX-2 negative group (n = 54 patients) and the COX-2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX-2 positive group were compared with data from the patients in the COX-2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival.


RESULTS
In the immunohistochemical study, COX-2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX-2 positive group was much higher compared with the treatment failure rate of patients in the COX-2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX-2 positive group was statistically significant (48% for the COX-2 positive group vs. 13% for the COX-2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX-2 positive group vs. 7% for the COX-2 negative group). In addition, increased COX-2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX-2 positive group vs. 26 months in the COX-2 negative group). Compared with patients in the COX-2 negative group, patients in the COX-2 positive group had lower overall actuarial and disease free survival rates (overall 5-year actuarial survival rates: 56% for the COX-2 positive group vs. 94% for the COX-2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX-2 overexpression was an independent prognostic factor that surpassed other well-known clinicopathologic parameters.


CONCLUSIONS
COX-2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy.
Kim
Yong Bae
YB
Department of Radiation Oncology, Yonsei Cancer Center, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seodaemoon-Gu, Shinchon-Dong, 134 Seoul 120-752, Korea.
Kim
Gwi Eon
GE
Cho
Nam Hoon
NH
Pyo
Hong Ryull
HR
Shim
Su Jung
SJ
Chang
Sei Kyung
SK
Park
Hee Chul
HC
Suh
Chang Ok
CO
Park
Tchan Kyu
TK
Kim
Byung Soo
BS
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases