Overexpression of p53 is not associated with drug resistance of gastric cancers to 5-fluorouracil-based systemic chemotherapy.
OBJECTIVE
Recent in vitro evidence has strongly suggested that most anti-cancer drugs exert their cytotoxic effects via a p53-dependent apoptosis pathway. An intact p53 molecule appears to be a prerequisite for the cancer cells to be susceptible to these drugs. In this study, we specifically examined if overexpression of p53 may confer drug resistance on human gastric cancer.


METHODS
All patients were treated by an empirical HDFL regimen (weekly 24-hour infusion of 5-FU, 2,600 mg/m2 and leucovorin, 300 mg/m2) in a prospective phase II clinical trial. Among them, patients with adequate pre-chemotherapy gastric cancer tissues for immunohistochemical studies were selected for this study. A p53 DO7 monoclonal antibody was used to detect the overexpression of p53. The results were designated as "-" or "+" by the independent interpretation of two pathologists.


RESULTS
A total of 30 patients, 18 men and 12 women, with a median age of 61.5 years (range: 32-78 years), were studied. There were 15 responders and 15 non-responders to HDFL chemotherapy. The percentage of p53 overexpression with positive DO7 staining was 20.0% (6 out of 30). There were no significant differences in the pertinent clinicopathologic features between the patients with positive staining of p53 and the patients with negative staining of p53. Three out of 6 (50.0%) patients with positive staining of p53 and 12 out of 24 (50.0%) patients with negative staining of p53 responded to chemotherapy, respectively (p = 1.000 by Fisher's exact test).


CONCLUSIONS
Our data suggested that the overexpression of p53 does not predict drug resistance to 5-FU of human gastric cancer.
Yeh
K H
KH
Department of Oncology, University Hospital, Taipei, Taiwan, ROC.
Shun
C T
CT
Chen
C L
CL
Lin
J T
JT
Lee
W J
WJ
Lee
P H
PH
Chen
Y C
YC
Cheng
A L
AL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil