Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients.
OBJECTIVE
To investigate the expression of cyclooxygenase (COX-2) and its association with clinicopathologic parameters and clinical outcome in patients with cervical cancer.


METHODS
The study included 84 patients with stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21) underwent radical surgery, whereas patients with locally advanced cervical cancer (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and subjected to surgery in case of response. Immunohistochemical analysis was performed on paraffin-embedded sections with rabbit antiserum against COX-2.


RESULTS
COX-2--integrated density values in the overall population ranged from 1.2 to 82.3, with mean plus minus SE values of 27.4 plus minus 2.4. According to the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive. COX-2 levels were shown to be highly associated with tumor susceptibility to neoadjuvant treatment. COX-2 showed a progressive increase from mean plus minus SE values of 19.9 plus minus 8.0 in complete responders through 31.5 plus minus 3.5 in partial responses to 44.8 plus minus 3.9 in patients who were not responsive (P =.0054). When logistic regression was applied, only advanced stage and COX-2 positivity retained independent roles in predicting a poor chance of response to treatment. COX-2--positive patients had a shorter overall survival (OS) rate than COX-2--negative patients. In patients with LACC, the 2-year OS rate was 38% in COX-2--positive versus 85% in COX-2--negative patients (P =.0001). In the multivariate analysis, only advanced stage and COX-2 positivity retained independent negative prognostic roles for OS.


CONCLUSIONS
The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.
Ferrandina
G
G
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Lauriola
L
L
Distefano
M G
MG
Zannoni
G F
GF
Gessi
M
M
Legge
F
F
Maggiano
N
N
Mancuso
S
S
Capelli
A
A
Scambia
G
G
Ranelletti
F O
FO
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2; D019008:Drug Resistance, Neoplasm; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011817:Rabbits; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002945:Cisplatin