Prognostic significance of vascular endothelial growth factor and cyclooxygenase-2 in patients with rectal cancer treated with preoperative radiotherapy.
OBJECTIVE
To analyze the prognostic value of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in patients with locally advanced rectal cancer treated with preoperative radiotherapy.


METHODS
Eighty-one patients with locally advanced rectal cancer were studied. All patients received preoperative pelvic radiotherapy. Forty-seven patients received concomitant chemotherapy. Surgical resection was performed 4-8 weeks later in all patients. Immunohistochemical examination of COX-2 and VEGF was performed on the preirradiation diagnostic biopsies. An immunohistochemical score established from the extension and intensity of the markers was used for analysis. The log-rank test and proportional hazards regression analysis were used to calculate the probability that the biomarkers were associated with patient outcome.


RESULTS
COX-2 expression was positive in 38 tumors (51%) while VEGF expression was positive in 43 (57%). The only clinicopathological parameter significantly associated with COX-2 or VEGF expression was performance status. None of the 2 markers were found to predict treatment response. There was no statistically significant correlation between COX-2 and VEGF. Univariate analysis identified pathological stage (pT, pN) as prognostic for disease-free survival. When VEGF expression was analyzed, disease-free survival was reduced among patients with VEGF-positive tumors (p = 0.047). This was specifically related to metastases-free survival (p = 0.016). These results were not observed for COX-2. After multivariate analysis, the pT and pN stage remained as independent prognostic factors.


CONCLUSIONS
VEGF-positive expression is an indicator of poor disease-free survival, specifically linked to distant metastasis. More aggressive treatment strategies are warranted in pT3-4 and pN1-2 rectal cancer patients.
Giralt
Jordi
J
Department of Radiation Oncology, Hospital Vall d'Hebron, Barcelona, Spain. jgiralt@vhebron.net
Navalpotro
Begoña
B
Hermosilla
Eduardo
E
de Torres
Ines
I
Espin
Eloi
E
Reyes
Victoria
V
Cerezo
Laura
L
de las Heras
Manuel
M
Ramon y Cajal
Santiago
S
Armengol
Manel
M
Benavente
Sergi
S
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2