P53 protein expression in gastric adenocarcinoma. Negative predictor of survival after postoperative adjuvant chemotherapy.
BACKGROUND
The aim of the present study was to evaluate the influence of p53 protein on the survival of patients undergoing radical gastrectomy and postoperative adjuvant chemotherapy for gastric cancer.


METHODS
It was a retrospective study of 46 patients with gastric adenocarcinoma (Stage II and III of the Japanese staging system). Alypatients were treated by curative radical gastrectomy with regional lymphadenectomy plus adjuvant chemotherapy. This regime included Mitomycin (20 mg one hour before surgery, followed by 10 mg the day after) and Fluorinated Pyrimidine (UFT) (400 mg/m2/day orally) (started four weeks after operation, and continued for one year). Immunohistochemical expression of p53 protein was determined on tumor samples from the removed specimens. The influence of p53 on survival was assessed in a Cox's proportional hazard regression analysis.


RESULTS
Sixteen tumors (34.7%) manifested nuclear overexpression of p53 protein. Patients with p53-negative tumors showed higher cumulative survival at 4 years follow-up than patients with p53-positive tumors (82% versus 45%) (p < 0.01). Multivariate analysis identified p53 overexpression as a negative independent predictive factor (hazard ratio: 11.15) (95% CI: 1.93-64.42). Multivariate analysis performed on patients with Stage III tumors, separately, confirmed the predictive effect of p53 overexpression.


CONCLUSIONS
The results suggest that postoperative adjuvant chemotherapy acted differently in p53-positive than in p53-negative gastric tumors. Absence of p53 overexpression is associated to longer survival when adjuvant therapy is administered.
Department of Surgery, University of Alcalá de Henares, General of Surgery, Hospital Principe de Asturias, Madrid, Spain. mdiez@hupa.insalud.es
M
M
Díez
M J
MJ
Medrano
A
A
Gutierrez
A
A
López
J M
JM
Mugüerza
P
P
Hernández
O
O
Lozano
F
F
Noguerales
A
A
Ruíz
J
J
Granell
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012044:Regression Analysis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin