Characterisation and clinicopathological correlates of serum anti-p53 antibodies in breast and colon cancer

Coomber, David; Hawkins, Nicholas J.; Clark, Michelle A.; Meagher, Alan P.; Ward, Robyn L.

doi:10.1007/bf01209124

Cited by 22 publications

(18 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 60%

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

Tang

Wang

et al. 2001

Int. J. Cancer

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 60%

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

Tang

Wang

et al. 2001

Int. J. Cancer

View full text Add to dashboard Cite

show abstract

“…Presence of anti-p53 serum antibodies is regarded as a bad prognostic factor in breast and head and neck cancer, or as an increased risk for relapse but not death in ovarian and colon cancer (Schlichtholz et al, 1992;Houbiers et al, 1995;Angelopoulou et al, 1996;Bourhis et al, 1996;Coomber et al, 1996). As previously mentioned, eight patients of our series operated for HCC had antip53 serum antibodies, and at least one factor of bad prognosis as defined by the experience of different groups (Akashi et al, 1991;Yamashita et al, 1991;Bismuth et al, 1993;Ganne-CariŽ et al, 1996).…”

Section: Discussionmentioning

confidence: 48%

“…More recently, serum antibodies reacting with the p53 protein have been detected in cancer patients with a variety of neoplasms (Schlichtholz et al, 1992;Angelopoulou et al, 1994Angelopoulou et al, , 1996Volkmann et al, 1993;Houbiers et al, 1995;Lubin et al, 1995a, b;Bourhis et al, 1996;Coomber et al, 1996;Gadducci et al, 1996;Ryder et al, 1996;Wild et al, 1995). A prerequisite for a B-cell response seems to be the accumulation in the tumour of a mutant or, less frequently, a wild-type p53 protein.…”

mentioning

confidence: 99%

“…A prerequisite for a B-cell response seems to be the accumulation in the tumour of a mutant or, less frequently, a wild-type p53 protein. Anti-p53 serum antibodies have been associated with poor prognosis and advanced stage in breast (Schlichtholz et al, 1992;Angelopoulou et al, 1996), head and neck (Bourhis et al, 1996), colorectal (Houbiers et al, 1995;Coomber et al, 1996) and ovarian (Angelopoulou et al, 1996;Gadducci et al, 1996) cancers. However, serological assessment of anti-p53 antibodies seems also to allow detection of tumours at an early and therefore more treatable stage (Lubin et al, 1995b;Trivers et al, 1995Trivers et al, , 1996.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

et al. 1999

View full text Add to dashboard Cite

Summary p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12-30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alphafetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative 'good prognosis' in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis.

show abstract

“…41 Of the individuals with a humoral response to p53, most have antibodies against the immunodominant amino-terminal and carboxy-terminal regions. [42][43][44][45][46] The secondary structure of these regions remains unchanged in mutant forms of the protein, suggesting that the immune response is more likely to be due to accumulation of the protein than to the appearance of novel antigenic determinants by mutation. Several other studies have identified patients with anti-p53 antibodies but no identifiable accumulation of p53 in their tumors.…”

Section: Discussionmentioning

confidence: 99%

A High Degree of Aneuploidy, Loss of p53 Gene, and Low Soluble p53 Protein Serum Levels Are Detected in Ulcerative Colitis Patients

Rosman-Urbach¹,

Niv²,

Birk³

et al. 2004

Diseases of the Colon &Amp; Rectum

View full text Add to dashboard Cite

We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.

show abstract

Characterisation and clinicopathological correlates of serum anti-p53 antibodies in breast and colon cancer

Cited by 22 publications

References 21 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

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

A High Degree of Aneuploidy, Loss of p53 Gene, and Low Soluble p53 Protein Serum Levels Are Detected in Ulcerative Colitis Patients

Contact Info

Product

Resources

About