Influence of tumor localization on the prognostic value of P53 protein in colorectal adenocarcinomas.
BACKGROUND
The prevalence of genetic alterations is different in primary carcinomas from the proximal colon when compared with carcinomas from the distal colorectum. The objective of this work was to explore the existence of possible differences in the informative weight of the risk of tumor recurrence provided by p53 immunostaining depending on the localization of the neoplasm.


METHODS
Nuclear immunohistochemical expression of p53 protein was determined in formalin-fixed paraffin-embedded archival tumor tissue samples from 190 primary colorectal adenocarcinomas. The relative prognostic importance on the risk of recurrence of each variable was assessed in a Cox's proportional hazard regression analysis. Multiplicative interaction terms between p53 and tumor site were included in the multivariate models in order to test their joint effect on survival.


RESULTS
One hundred and one patients (53.1%) manifested nuclear accumulation of the protein. P53 overexpression was more frequent in distal than in proximal tumors (58.5% ve s 41.7%) (p = 0.03). Disease-free survival was lower in p53-positive cases (75% versus 38%) (p = 0.006), but significance of the association varied according to the localization of the tumor (p = 0.004 in proximal carcinomas and p = 0.049 in distal carcinomas). Multivariate analysis identified p53 positivity and distal tumor localization as the factors significantly associated with a high risk of recurrence Interaction between p53 expression and localization was present. P53 exhibited different prognostic value in distal and proximal colon. While adjusted hazard ratio for positive p53 was 1.99 in distal cancers, it was 8.04 for proximal tumors.


CONCLUSIONS
The prognostic with value of tumor recurrence associated overexpression of p53 protein is influenced by the location of the tumor. The negative predictive weight is significantly higher in proximal than in distal cancers.
Hospital Principe de Asturias, Alcalá de Henares, 28808 Madrid, Spain. mdiez@hupa.insalud.es
M
M
Diez
M
M
Medrano
J M
JM
Mugüerza
P
P
Ramos
P
P
Hernandez
R
R
Villeta
A
A
Martín
F
F
Noguerales
A
A
Ruiz
J
J
Granell
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002467:Cell Nucleus / Q000473:pathology; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53