Loading…
High Cyclooxygenase-2 Expression Following Neoadjuvant Radiochemotherapy Is Associated with Minor Histopathologic Response and Poor Prognosis in Esophageal Cancer
Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer. Experimental Design: Fift...
Saved in:
Published in: | Clinical cancer research 2005-12, Vol.11 (23), p.8341-8347 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed
the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal
cancer.
Experimental Design: Fifty-two patients with resectable esophageal cancers (cT2-4, N x , and M 0 ) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy.
Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital
tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative
real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for β-actin.
COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining
of tumor cells.
Results: Median COX-2 mRNA expression levels were significantly ( P < 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pre-therapeutic
and posttherapeutic specimens showed a significant difference ( P < 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2
protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens
was significantly associated with minor histopathologic response ( P < 0.04) and poor prognosis (5-year survival probabilities: 26.3 ± 8.2% for minor and 58.6% ± 12.9% for major histopathologic
response; P < 0.01).
Conclusion: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated
with minor histopathologic response to neoadjuvant therapy and very poor prognosis. |
---|---|
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-2373 |