Cyclooxygenase-2 (COX-2) levels before and after chemotherapy: a study in rectal cancer.
OBJECTIVE
Induction of cyclooxygenase-2 (COX-2) by inflammatory mediators, oncogenes, and carcinogens has been demonstrated in preclinical models. However, there are limited clinical data regarding COX-2 induction by chemotherapy or radiation. Experimental data suggest cross-talk between the EGFR and COX-2 pathways. The aim of this study was to analyze the expression of COX-2 before and after chemoradiation (CRT) and correlate the same with tumor (T) down-staging and survival. Similar data were obtained for EGFR expression before and after chemoradiation.


METHODS
Archival paraffin-embedded tumor specimens from patients undergoing CRT between 1995 and 2001 were analyzed. COX-2 expression was measured by immunohistochemistry (IHC), using the 160112 COX-2 mouse monoclonal antibody. For EGFR, we used mouse monoclonal Ab-10. Standard immunoperoxidase technique was used to detect the avidin- biotin peroxidase complex. Staining in tumor tissue was visually scored and confirmed by an image analyzer (ACIS; ChromaVision Medical Systems, Inc, San Juan Capistrano, CA).


RESULTS
Twenty pretreatment biopsy samples from rectal cancer patients and their paired, post-CRT surgical specimens (n = 17) were analyzed. Three cases had no primary tumor after CRT. COX-2 expression was noted in 19 of 20 pretreatment samples and 17 of 17 surgical specimens. EGFR expression was noted in 10 cases pretreatment. Six patients with weakly positive COX-2 expression pretreatment had increased COX-2 expression after CRT, whereas in 1 patient the expression decreased after CRT. No EGFR induction was noted. There was no statistical association between EGFR and COX-2 expression in this data set. Median survival for the entire cohort was 38.9 months. There was no difference in survival between the COX-2 induced and noninduced groups.


CONCLUSIONS
COX-2 induction was seen with CRT in this population of rectal cancer patients. Prognostic significance of this induction remains to be defined in a larger cohort.
Watwe
Veena
V
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Javle
Milind
M
Lawrence
David
D
Groth
Jeffrey
J
Iyer
Renuka
R
El-Hajjar
Dany
D
Geradts
Joseph
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001706:Biopsy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D004790:Enzyme Induction; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015993:Life Tables; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D066246:ErbB Receptors; D005472:Fluorouracil