[Variation in the prognostic value of p53 protein in relation to tumoral stage in patients with colorectal adenocarcinoma].
OBJECTIVE
To analyze the prognostic value of p53 protein as a marker of recurrence risk in each tumoral stage.


METHODS
A prospective study of a cohort of 288 patients who underwent surgery for colorectal adenocarcinoma was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%). Histopathological variables were examined in tumor samples fixed in formol and embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The results of p53 were analyzed in each of the categories of clinical and histopathological variables. Recurrence-free survival was calculated using the Kaplan-Meier method. The value of each variable as a predictive marker for tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and 95% confidence intervals were calculated as indicators of relative risk. The analysis was applied to the whole cohort and was subsequently repeated in each TNM tumoral stage separately.


RESULTS
Tumors with p53 protein overexpression more frequently recurred and showed lower recurrence-free survival at 5 years. However, the association between p53 expression and postoperative outcome was statistically significant in stage III tumors only. In this subgroup of patients, recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26% in p53-positive tumors (p=0.010). In the multivariate analysis, p53 was an independent prognostic factor associated with a high risk of recurrence in stage III tumors (hazard ratio=2.76; 95% CI, 1.29-5.9; p=0.009). Overexpression of p53 showed prognostic value as a marker of high risk of recurrence in the form of metastases (hazard ratio=2.23; 95% CI, 1.04-4.75), but not as a prognostic marker of locoregional recurrence. No relationship was found between the state of p53 protein and the effect of postoperative adjuvant therapy.


CONCLUSIONS
The p53 protein does not have the same prognostic value in all tumoral stages. This protein is only predictive of high recurrence risk in the subgroup of patients with stage III tumors.
Díez
Manuel
M
Departamento de Cirugía, Universidad de Alcalá, Hospital Príncipe de Asturias, Madrid, Spain. mdiez.hupa@salud.madrid.org
Pollán
Marina
M
Ramos
Paloma
P
Villeta
Rafael
R
Ratia
Tomás
T
Hernández
Pilar
P
Lozano
Oscar
O
Noguerales
Fernando
F
Granell
Javier
J
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D000368:Aged; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53