COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy.
OBJECTIVE
To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT).


METHODS
Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis.


RESULTS
Good response (TRG 1+2), moderate response (TRG 3), and poor response (TRG 4+5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3+4) to treatment than were those with normal COX-2 expression (p=0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p=0.0007, chi-square test).


CONCLUSIONS
COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.
Smith
Fraser M
FM
Department of Surgery, St. James's Hospital, Dublin, Ireland.
Reynolds
John V
JV
Kay
Elaine W
EW
Crotty
Paul
P
Murphy
James O
JO
Hollywood
Donal
D
Gaffney
Eoin F
EF
Stephens
Richard B
RB
Kennedy
M John
MJ
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D012007:Rectum / Q000473:pathology; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D051546:Cyclooxygenase 2