COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):466-72. doi: 10.1016/j.ijrobp.2005.07.961. Epub 2005 Oct 5.

Abstract

Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT).

Methods and materials: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Cyclooxygenase 2 / analysis*
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Male
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / enzymology*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy
  • Rectum / pathology
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Cyclooxygenase 2