Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal: a report of randomized trial RTOG 87-04. Radiation Therapy Oncology Group.
BACKGROUND
Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal, approximately 20% of patients will develop a local recurrence. This study examined the prognostic significance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the anal canal.


METHODS
All patients were treated in a prospective, randomized Radiation Therapy Oncology Group trial (RTOG 87-04) in which radiotherapy to the pelvis was compared with concurrent 5-fluorouracil (5-FU) or 5-FU and mitomycin-C. Formalin fixed, paraffin embedded blocks or unstained slides from the pretreatment biopsies of 64 patients were obtained from referring institutions and evaluated immunohistochemically with the polyclonal p53 antibody CM-1. A multivariate analysis was conducted to analyze overexpression of p53 in terms of locoregional control, no evidence of disease (NED), and overall survival.


RESULTS
p53 protein was overexpressed in 48.4% of the cases. Although not statistically significant, there was a trend for patients whose tumors overexpressed p53 to have inferior locoregional control (52% vs. 72%, P = 0.13), NED survival (52% vs. 68%, P = 0.27), and absolute survival (58% vs. 78%, P = 0.14). Of all the pretreatment factors analyzed, only International Union Against Cancer stage was predictive of outcome in multivariate analysis. Among those patients whose tumors overexpressed p53, there was a trend toward improved outcome in the arm that received 5-FU and mitomycin-C compared with the arm that received 5-FU only.


CONCLUSIONS
Overexpression of the p53 protein may be associated with inferior outcome for patients managed with definitive chemoradiation for epidermoid carcinoma of the anal canal.
Bonin
S R
SR
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Pajak
T F
TF
Russell
A H
AH
Coia
L R
LR
Paris
K J
KJ
Flam
M S
MS
Sauter
E R
ER
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008937:Mitomycins / Q000008:administration & dosage; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D008937:Mitomycins; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil