Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma.
BACKGROUND
Inactivation of the p53 gene has been reported to be associated with resistance to chemotherapy. The authors evaluated the significance of p53 status to the clinical outcomes of patients with locally advanced, unresectable gastric carcinoma (LAGC) who received chemotherapy.


METHODS
Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m2, epi-doxorubicin 35 mg/m2, 5-fluorouracil 500 mg/m2, 6S-leucovorin 250 mg/m2, and glutathione 1500 mg/m2. After eight administrations of these agents, patients were assessed for response. Biopsy specimens of primary tumors were analyzed for p53 status using monoclonal antibody Bp53-12.


RESULTS
Characteristics of patients were as follows: The median age was 66 years (range, 44-70 years); 18 were males and 12 were females. Eastern Cooperative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was diffuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (assessed with CT scan and endoscopy) for patients with p53 negative tumors was significantly higher than for those with overexpression of p53 (71% vs. 12%, P=0.004).


CONCLUSIONS
p53 status analyzed before chemotherapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant chemotherapy for these patients.
Cascinu
S
S
Department of Hematology/Oncology, Azienda Ospedaliera S. Salvatore, Pesaro, Italy.
Graziano
F
F
Del Ferro
E
E
Staccioli
M P
MP
Ligi
M
M
Carnevali
A
A
Muretto
P
P
Catalano
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care / Q000379:methods*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil