Prognostic value of immunohistochemistry for p53 in primary soft-tissue sarcomas: a multivariate analysis of five antibodies.
Most changes of tumor suppressor p53 and its pathway involve a protein with prolonged half-life that permits immunohistochemical detection. The goal of this study was to compare the prognostic relevance of five different p53 antibodies in primary soft-tissue sarcomas (STS) with known p53 mutation status, using a multivariate Cox regression model (adjusted to tumor grading, staging, localization, tumor type, and therapy). A group of 198 primary STS of six types were investigated for p53 overexpression, using p53 antibodies DO-1, DO-7, Pab1801, Pab240, and CM-1. A positive marker frequency between 36.2% and 62.6% was detected. Out of 65 patients whose primary tumor reacted positively to all five antibodies, 52 (80%) died within the study period. Only the N-terminal-binding monoclonal antibodies DO-1, DO-7 and Pab1801 showed a multivariate correlation with survival (P = 0.0014, 0.0048 and 0.02). CM-1 and Pab240 had a univariate, but not a multivariate correlation, with a confounding effect of grading. The prognostic relevance for the five p53 antibodies was: DO-1 > Pab1801 > DO-7 > CM-1 > Pab240. This is the first study that investigates multivariately the prognostic relevance of p53 immunostaining in STS. If monoclonal antibodies with an epitope in the N-terminal region of the p53 protein (DO-1, Pab1801, DO-7) are applied, p53 immunohistochemistry provides an independent prognostic marker in STS.
Würl
P
P
Clinic of General Surgery, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany.
Taubert
H
H
Meye
A
A
Berger
D
D
Lautenschläger
C
C
Holzhausen
H J
HJ
Schmidt
H
H
Kalthoff
H
H
Rath
F W
FW
Dralle
H
H
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D015999:Multivariate Analysis; D011379:Prognosis; D012509:Sarcoma / Q000175:diagnosis*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D016159:Tumor Suppressor Protein p53