Comparison
of p53 antibody status and carcinoembryonic antigen (CEA) levels and their
clinical impact as diagnostic markers in colorectal cancer patients
Gasser M, Bueter M, Meyer D, Gassel AM1, Thiede
A, Waaga-Gasser AM
Dept.
of Surgery, Molecular Oncoimmunology; 1Dept. of Pathology, Univ.
of Wuerzburg
waaga-gasser@chirurgie.uni-wuerzburg.de
To evaluate the clinical impact of p53 antibodies
(Ab), suggested to be associated with advanced tumor state and poor survival,
we analyzed the frequency
of circulating anti-p53 Ab, levels of free p53 protein, concentration of CEA
in sera of colorectal
cancer patients (n=48), expression of p53/CEA in tumors and correlated with
UICC stage. 39.6% of all patients (n=19/48)
expressed wild-type (wt) p53-specific-IgG-Ab (26% UICC I n=5/19, 16% UICC
II 3/19, 21% UICC III 4/19, 37% UICC IV 7/19). 31.3% showed a negative response
(n=15/48) and 29.2% were within the critical range (n=14/48). In addition,
similar levels of p53-IgG1/IgG2 were observed in patients with p53 Ab (ELISA).
No correlation was found between free p53 protein and antibody levels. Immunohistologically
62.5% of the tumors overexpressed p53 (clone DO-7, n=10/16) independent of
UICC stage. The presence of wt p53-IgG-Ab was correlated with strong p53 staining
within the tumor. In addition, 29.2% of the patients expressed high CEA levels
(n=14/48) depending on UICC stage (UICC I n=0/6, UICC II 0/12, UICC III 2/9,
UICC IV 12/21, ELISA). CEA expression within the tumor and UICC stage was
strongly correlated (75%, n=12/16). Five different point mutations at 5 different positions
of wt p53 sequence (4 in DNA-binding core domain) were observed in tumors (n=16, RT-PCR). This study suggests that a humoral
response to p53 is strongly correlated with intracellular accumulation of
p53 but independent from free p53 protein and p53 gene mutations. In contrast
to CEA, presence of p53 auto-Ab is not correlated with UICC stage. p53 auto-Ab seem not to be predictive in poor
outcome and irrelevant in colorectal cancer diagnosis.