Detection and monitoring of serum p53 antibodies in patients with colorectal cancer.

Hammel, Pascal; Boissier, Brigitte; Chaumette, Marie-Thérèse; Piedbois, Pascal; Rotman, N; Kouyoumdjian, Jean‐Claude; Lubin, R.; Delchier, Jean‐Charles; Soussi, Thierry

doi:10.1136/gut.40.3.356

Cited by 79 publications

(55 citation statements)

References 18 publications

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“…21,22 In the current study, the proportion (13%) of seropositive patients is consistent with a previous report on CRC 15 but represents a lower figure than other studies reporting positivity rates varying from 18 to 32%. 16,18,20,[23][24][25] In a previous study, 26 we reported that Taiwan had the lowest frequency of p53 mutations (31%) and the highest frameshift mutation rates among various population studies, which agrees with half of the CRC patients with a p53 mutation in the tumor having circulating p53-Abs. 3 In accordance with other studies, 18,23,25-27 in our series, we found no correlation with demographic or clinicopathologic features, except for tumor location and nodal status of the tumor.…”

Section: Discussionsupporting

confidence: 57%

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Tang

Wang

et al. 2001

Int. J. Cancer

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p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/L), low (10 -76 U/L) and high (>76 U/L). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] ‫؍‬ 3.4; 95% CI ‫؍‬ 1.1-10.5), the rectum (OR ‫؍‬ 2.9; 95% CI, 1.0 -8.8) and advanced lymph node metastasis (OR ‫؍‬ 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p ‫؍‬ 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.

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Section: Discussionsupporting

confidence: 57%

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Tang

Wang

et al. 2001

Int. J. Cancer

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“…28 Therefore, it remains to be seen whether the intracellular antigens recognized by our phage antibodies are identical to the antigens described for the SEREX procedure. 37 Our data do not rule out the existence of humoral responses to certain cell surface antigens, as has been reported by others, 32,40,41 but they do show that there is a large bias toward intracellular 4,35,42,43 targets. It remains to be determined whether such epithelial cell-specific, somatically hypermutated antibodies are also found in other CRC patients.…”

Section: Discussioncontrasting

confidence: 42%

Evidence for a bias toward intracellular antigens in the local humoral anti-tumor immune response of a colorectal cancer patient revealed by phage display

et al. 2001

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Many patients with colorectal carcinoma (CRC) mount a cellular as well as a humoral immune response to the tumor. To investigate the nature and specificity of the humoral immune response in a CRC patient, lymphocytes infiltrating the primary colorectal tumor and lymph nodes draining the tumor were used as antibody variable (V)-gene pools for the construction of phage antibody repertoires. These libraries were first validated by selection on the antigen tetanus toxoid and shown to contain antibodies that were probably derived from both naive and memory B cells. The repertoires were then screened for the presence of antibodies directed to CRC by selection on the cell line CaCo2. For comparison, the same selections were performed with a phage antibody repertoire made from B cells of healthy donors. Striking differences were observed in the panel of specificities selected from these different repertoires: although a large panel of antibodies reactive with patient-derived primary tumors was obtained from the immune repertoires, none of these discriminated between normal colonic epithelium and colon cancer and none were reactive with cell-surface antigens. However, selections using the non-immune library did result in numerous antibodies that recognized cell surface markers on CaCo2. These data suggest a bias in the local humoral immune response in this CRC patient, directed primarily toward intracellular epithelial-cell specific target antigens.

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“…It has previously been shown that p53-Abs can be used for monitoring the follow-up of patients during therapy (Hammel et al, 1997;Polge et al, 1998;Zalcman et al, 1998). The presence of p73-Abs was tested in a series of patients for whom serum was available during therapy (data not shown, patients diffrent from those described in Table 1).…”

Section: P73 Antibodies and Follow-upmentioning

confidence: 99%

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

et al. 2001

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Summary p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino-and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells.

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Detection and monitoring of serum p53 antibodies in patients with colorectal cancer.

Abstract: Background-Detection of p53 antibodies in serum might be an effective indirect procedure to detect alterations of the p53

Cited by 79 publications

References 18 publications

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Evidence for a bias toward intracellular antigens in the local humoral anti-tumor immune response of a colorectal cancer patient revealed by phage display

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

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