p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM.     

Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study.

Anti-p53 antibodies in sera are known to be products of the host immune response to mutated p53 protein, and are present in some patients with various types of cancer. In this study, we measured serum anti-p53 antibody levels in 52 patients with lung cancer and 63 normal volunteers to determine the relationship between anti-p53 antibody level and clinical features of lung cancer patients. Anti-p53 antibody level was measured by an enzyme-linked immunosorbent assay and expressed as an anti-p53 antibody index, defined as the ratio of absorption of serum sample to that of p53-positive serum. The median anti-p53 antibody index was 6.6 for lung cancer patients, and higher than that in normal volunteers (1.7) (P = 0.0000). For lung cancer patients, significant differences in index levels were found by histology (4.3, n = 25, adenocarcinoma vs 8.7, n = 18, squamous cell carcinoma vs 64.8, n = 2, large-cell carcinoma vs 9.8, n = 7, small-cell carcinoma; P = 0.0109). High anti-p53 antibody index levels were observed for both large-cell carcinoma and small-cell carcinoma. When the cut-off level was set at 7.2, determined using the twice 95% specificity level for normal volunteers, the sensitivities of anti-p53 antibodies were 46.1% for all lung cancers, 28.0% for adenocarcinoma, 55.6% for squamous cell carcinoma, 100% for large-cell carcinoma and 71.4% for small-cell carcinoma. However, there were no significant differences in index level by gender, age, smoking index, presence of previous or concomitant cancer or disease stage. Multivariate analysis using a logistic regression model demonstrated that histological type of tumour was a dominant factor associated with elevation of anti-p53 antibody index level (P = 0.0184). These findings suggest that serum anti-p53 antibody index level might be independent of tumour burden and the presence of previous or concomitant cancer in our series of lung cancer patients, but is clearly strongly correlated with tumour histological type.     

血清p53抗体水平与肺癌临床指标关系的研究

目的：通过对肺癌患者血清Ｐ５３抗体水平与肺癌临床指标关系的研究，探讨血清ｐ５３抗体在肺癌中的临床意义。方法对６８例肺癌患者应用ＥＬＩＳＡ法检测血清Ｐ５３抗体滴度，经酶联免疫检测仪测吸光值Ｅ４５０，计算抗体指数，进行统计学分析。结果６８例中阳性３２例，阳性率为４７．１％，血清Ｐ５３抗体水平与肺癌的一般临床特征，如性别、分期、吸烟指数、既往治疗均无关，而与肺癌的病理类型和肿块大小有关。结论Ｐ５３抗体的     

Serum anti-p53 antibodies in gastric adenocarcinoma patients are associated with poor prognosis, lymph node metastasis and poorly differentiated nuclear grade.

Mutation of the p53 tumour suppressor gene often leads to the accumulation of mutant p53 protein in tumour cells. Many cancer patients develop antibodies that recognize the overexpressed p53 protein. The presence of these antibodies is, in some tumour types, associated with poor prognosis. Gastric cancer is a highly prevalent disease associated with a high rate of mortality, there is a need for improved clinical and biological markers for disease behaviour. To investigate the clinical relevance of serum anti-p53 antibodies in patients with gastric adenocarcinoma, we have examined the sera of 501 gastric cancer patients for the presence of serum antibodies against the p53 protein. By immunoblotting analysis using a cell lysate containing overexpressed p53 protein as well as affinity-purified recombinant p53 protein as antigens, we have detected anti-p53 antibodies in 11.2% (61 of 501) of gastric cancer patients, but in none of 46 cancer-free individuals. The presence of anti-p53 antibodies was tightly associated with tumours of higher nuclear grade and lymph node metastasis, and a negative association was found between the presence of anti-p53 antibodies and survival. These results suggest that a preoperative test of serum anti-p53 antibodies in gastric cancer patients can be useful to identify subset of patients who may need gastrectomy with lymph node dissection and post-operative adjuvant therapy.     

p53 protein is absent from the serum of patients with lung cancer.

p53 protein, which accumulates intracellularly in over half of all human tumours, has also been reported to be present in the sera of patients with various malignancies, including lung cancer. Using a quantitative immunoassay, we measured p53 protein concentrations in 216 sera from 114 lung cancer patients of whom 75 provided matched lung tumour tissues, which were also assayed for p53 protein. p53 protein levels above the detection limit of 0.04 ng ml-1 were detected in only two sera from lung cancer patients (0.14 ng ml-1 and 0.27 ng ml-1), but not in any of 13 sera from non-malignant lung disease patients or in 100 sera from normal non-diseased individuals. The presence of these apparent traces of serum p53 protein concentrations could not be related either to the p53 protein expression status of the primary lung tumours or to the tumour stage, grade or histological type. By pretreating these two sera with anti-p53 antibody linked to solid phase, and by the addition of mouse serum to neutralise possible heterophilic antibodies, the signals arising from these sera were shown to be non-specific and possibly caused by heterophilic antibodies. We conclude that our data do not support previous reports of p53 protein in the sera of lung cancer patients. Since immunoassays are subject to numerous sources of interference in serum, including heterophilic antibodies, we suggest that the results of p53 protein analysis of serum specimens should be interpreted with caution.     

Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation.

Using immunoblotting techniques we studied the sera from small cell lung cancer and non-small cell lung cancer patients for antibodies directed against p53. We have also characterized the majority of these patients' tumors for p53 mutations. In the sera of 13% of the patients (4 of 40 small cell lung cancer and 2 of 6 non-small cell lung cancer) we found antibodies specific for the p53 tumor suppressor gene product. All of the antibody-positive patients tested had p53 missense mutations and expressed detectable p53 antigen in their tumor cell lines. No anti-p53 antibodies were detected in sera from patients whose tumor had p53 stop, splice/stop, splice, or frameshift mutations (n = 10). Thus, while we find that the ability of lung cancer patients to develop anti-p53 antibodies is correlated with the type of p53 mutation, many patients have tumors with missense p53 mutations and did not develop anti-p53 antibodies. The presence of p53 antibodies was not correlated to stage, prior treatment, sex, or survival. None of these lung cancer patient sera had measurable amounts of p53 antigen. By immunoblotting all six anti-p53 antisera we were able to detect a variety of mutant p53 proteins (including those from antibody-negative patients) and detected wild-type p53 protein. The development of anti-p53 antibodies represents an interesting model system for studying immune responses in cancer patients against mutant oncogene products.     

Detection of serum anti-P53 antibodies from patients with colorectal cancer in China using a combination of P53- and phage-ELISA: correlation to clinical parameters

Background: Colorectal cancer is one of the most common malignant tumors in China. The aims of this research were to increase the sensitivity of anti-p53 antibody detection in the sera of patients with colorectal cancer and to assist in their diagnosis. Methods: Sixty-seven non-selected Chinese with colorectal cancer were involved in this study. Anti-p53 antibodies in serum were detected by ELISA using recombinant human wild-type p53 protein and hybrid phage as the coating antigen. Correlations between the anti-p53 antibodies and clinicopathological parameters were also analyzed. Results: The detection efficiency of anti-p53 antibodies in the patients with colorectal cancer was increased (46.3%, 31/67) through the combination of the two ELISA methods compared with each method alone. The titer of serum anti-p53 antibodies was not associated with clinicopathological parameters, but there was a significant correlation between their presence, the CEA level, and the stage of the patient’s colorectal cancer. Conclusions: These results demonstrate that combination of the two ELISA methods increased the detection rate of anti-p53 antibodies in patients with colorectal cancer. This research may provide a useful method to complement conventional clinical diagnosis.     

Correlations between p53-protein accumulation, serum antibodies and gene mutation in colorectal cancer.

Only half of colorectal-cancer patients elicit serum antibodies in response to intratumoral p53-gene mutations. Our study was designed to compare cellular events (p53-protein accumulation and gene mutations) with the presence of circulating anti-p53 antibodies (p53-Ab). Thirty-five colorectal-cancer patients were studied for their intratumoral p53-protein accumulation and circulating p53-Ab. Tumour DNA was analyzed for genomic mutations in a sub-set of 28 patients. In all, 18 tumours (51.4%) were positive by immunohistochemistry, and 17 tumour extracts were shown to contain "mutant" conformation p53 protein, 16 of them being were concordant by both methods. Of the 28 tumours tested by DGGE, 16 contained alterations in p53 exons 5 to 8 (57.1%). Of 12 tumours without detectable mutations, 10 were "mutant"-conformation-negative by immunohistochemistry and ELISA. Paradiploid tumors presented more frequently wild-type p53 genes and were significantly less frequently immunohistochemistry- or p53-Ab-positive than polyploid tumors. Circulating p53-Ab were detected in the serum of 11 patients (31%). In 9/11 cases, a gene mutation was found in the corresponding tumour. Three of four mutations in exon 8 and 3/3 mutations in exons 5-6 were associated with p53-Ab, in contrast with only 3/9 mutations in exon 7. We found good agreement in the detection of p53-gene alterations by different methods. However, our data suggest that all gene mutations may not be equivalent in term of immunogenicity.     

肺癌患者手术前后血清p53抗体的动态变化及其临床意义

目的 探讨肺癌患者血清ｐ５３抗体与临床病理特征之间的关系,以及手术后ｐ５３抗体的动态变化规律。方法 采用酶联免疫吸附法（ＥＬＩＳＡ）分别于术前１天、术后７、３０、９０天动态检测１２０例肺癌患者血清ｐ５３抗体,并以３０例肺部良性疾病患者和１２０例正常健康人作对照。结果 肺癌患者血清ｐ５３抗体水平和阳性率均明显６高于肺部良性疾病患者和正常人（Ｐ〈０．０５）,而正常人与肺部良笥疾病患者间无显著性差异（Ｐ     

Serum anti-p53 antibodies in uterine and ovarian cancer: association with dna sequence copy number abnormalities.

The aim of the present study was to evaluate the clinical significance of the serum anti-p53 antibody in patients with uterine and ovarian cancer. Some of the ovarian patients were also evaluated for overexpression of p53 by immunohistochemistry and for cytogenetic alterations by comparative genomic hybridization (CGH). Serum anti-p53 antibodies were determined by an enzyme immunoassay kit. The antibody was detected in 8/30 (27%) of ovarian cancers, in 12/86 (14%) cancers of the uterine cervix, in 5/41 (12%) cancers of the uterine body, and 0/9 (0%) healthy women. The overall survival rate in patients with ovarian cancer was significantly worse in patients with anti-p53 antibody positivity than that in patients with anti-p53-antibody-negative cancers using the log rank test (p = 0.017). There was a significant correlation between the presence of anti-p53 antibody and tissue overexpression of p53 in ovarian cancers. CGH analysis showed that the aberrations in DNA sequence copy number in ovarian cancers were significantly increased in anti-p53-antibody-positive cases compared to antip53-antibody-negative cases including increased copy number on 20q and reduced copy number on 5q and 13q. Although the exact relationship between the presence of serum anti-p53 antibody (specific humoral response) and cytogenetic alterations is still unknown, these findings suggest that the measurement of serum anti-p53 antibody may be useful for the assessment of genetic instability and tumor biological aggressiveness.     

p53抗体在Ⅲ期非小细胞肺癌手术前后的对照观察

目的 探讨血清p53抗体与Ⅲ期非小细胞肺癌临床病理特征之间的关系,并与组织中突变型p53蛋白进行对照.方法 正常组30例,肺良性疾病组10例,肺癌组45例,肺癌组分别于手术前1 d,术后10、30、60和90 d时抽取清晨空腹静脉血2 ml,其中23例肺癌病例于手术后120 d,15例病例于手术后180 d抽取清晨空腹...     

p53 antibodies in the sera of lung cancer patients: Comparison with p53 mutation in the tumour tissue

This study examined the sensitivity and specificity of serum auto-antibodies to p53 protein as a non-invasive marker of p53 genetic alterations or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine sera from 186 patients undergoing pulmonary surgery for a suspected lung cancer. Target antigens in ELISA were wild-type p53 protein and 5 peptides covering the N- and C-terminal parts of the protein. Sixteen sera were positive for serum p53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Of 50 patients with other pulmonary diseases, none had p53 antibodies. In 92 cancer patients exons 5 to 8 of the p53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCR products. Forty-seven tumours had a p53 mutation and 7 (15.2%) of these were positive for p53 antibodies. Two patients had serum antibodies but no detectable mutation in exons 5 to 8. Frequencies of p53 mutations and serum antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of p53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies. In conclusion, serum p53 antibodies were detected only in a proportion of lung cancer cases, but the majority were specifically associated with a detectable p53 mutation in the tumour. © 1995 Wiley-Liss, Inc.     

Levels of p53 antigen in the serum of nonsmall cell lung-cancer patients correlate with positive p53 immunohistochemistry on tumor sections, tumor necrosis and nodal involvement

We examined 50 non-small cell lung cancers and the matching serum from the same patients for the levels of p53 antigen. Histological sections of the tumor specimens were stained with anti-p53 specific antibodies, and the sera were tested by ELISA. We observed a correlation between the expression of the p53 protein in the tumors and the presence of circulating p53 antigen, using either a wild type-(P=0.024) or a mutant specific (P=0.007) ELISA test. The p53 serum levels were also significantly associated (P=0.019) with the extent of tumor necrosis, suggesting that circulating p53 may be derived by shedding from dead tumor cells. The levels of mutant p53 detected in the serum were significantly higher in patients with lymph node involvement (P=0.012) and with late-staged disease. (P=0.05). No association was found with tumor size and extent. Testing for serum levels of mutant p53 could provide additional prognostic information and could be used as as novel molecular diagnostic tool in the management of non-small cell lung cancer.     

Clinical implications of serum anti-p53 antibodies for patients with gastric carcinoma

BACKGROUND: Mutations of p53 can lead to the production of anti-p53 antibodies in sera of cancer patients. Before this study, the value of preoperative serum anti-p53 antibodies in determining the prognoses of patients with gastric carcinoma had yet to be determined. METHODS: The authors used a highly specific enzyme-linked immunosorbent assay (ELISA) kit (Pharma Cell, France) to determine the preoperative presence of serum anti-p53 antibodies in 120 patients with gastric carcinoma. The relation between the positivity of serum anti-p53 antibodies and p53 abnormal staining of gastric carcinoma tissues was examined. Clinicopathologic characteristics and prognoses of these patients were given attention. RESULTS: Anti-p53 antibodies were detected in 19.2%(23 of 120) of these patients with gastric carcinoma. Among those who were positive for anti-p53 antibodies, female patients were predominant, the depth of invasion was greater, and liver metastasis was present, as compared with those who were negative for anti-p53 antibodies. Regarding other factors, there were no differences between those who were positive or negative for anti-p53 antibodies. Gastric carcinoma tissues had a 60.9% (14 of 23) positivity rate of p53 staining with anti-p53 antibodies and a 33.0% (32 of 97) negativity rate, and this difference was statistically significant (P < 0.05). The survival time of patients with anti-p53 antibodies in their sera was shorter than that of subjects with sera negative for anti-p53 antibodies (P < 0.05). The presence of anti-p53 antibodies was not an independent prognostic factor in multivariate analysis. CONCLUSIONS: Serum assay of anti-p53 antibodies is a rapid and readily facilitated test for predicting tumor advancement, depth of invasion, and liver metastasis, and it will show a poorer prognosis for surgically treated patients with gastric carcinoma.     

Detection of serum anti-p53 antibodies from patients with ovarian cancer in China: correlation to clinical parameters

Background: Ovarian cancer has been one of the most common malignant tumor among women in China. The aims of this research were to increase the detection efficiency of anti-p53 antibodies in the sera from patients with ovarian cancer and to assist the diagnosis for patients with ovarian cancer. Methods: The hybrid phage displaying the immunodominant epitope SQAMDDLMLS in p53 N-terminal region was constructed and the fusion protein was prepared and purified. Ninety-two nonselected Chinese women with ovarian cancer were involved in this study. Tumor p53 overexpression was assessed by immunohistochemical analysis of tissue sections. Serum antibodies to p53 were also detected by enzyme-linked immunosorbent assay (ELISA) using recombinant human wild-type p53 protein and the hybrid phage as the coating antigen respectively. Furthermore, the correlations between the anti-p53 antibodies and clinicopathological parameters were analyzed. Results: The positive rate of anti-p53 antibodies in the patients with ovarian cancer was increased (39.1%, 36/92) through the combination of the two ELISA methods compared with each method. The anti-p53 antibodies were not associated with the clinicopathologic parameters, while there was a significant correlation between the presence of p53 Abs and tissue overexpression of p53 in ovarian cancer. Conclusion: These preliminary results demonstrate that the combination of the two ELISA methods increased the positive rate of anti-p53 antibodies in patients with ovarian cancer and provided a useful marker to complement routine clinical diagnosis for patients with ovarian cancer.     

Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies.

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism.     

The detection of serum anti-p53 antibodies from patients with gastric carcinoma in China

Background: Gastric carcinoma is one of the most frequently occurring cancers. The aim of this research was to increase the detection efficiency of anti-p53 antibodies in the sera of patients with gastric carcinoma and to improve the diagnosis for patients with gastric carcinoma. Methods: We prepared phage-displayed peptide DO7 and established an enzyme-linked immunosorbent assay method to detect the anti-p53 antibodies. We detected the anti-p53 antibodies of 61 patients with gastric carcinoma using the method and our previous ELISA method assisted by the recombinant wild-type human p53 protein to detect the anti-p53 antibodies. We studied the correlation between the anti-p53 antibodies and the clinicopathological data including sex, age, carcinoembryonic antigen, tumor size, tumor TNM staging, and lymph-node status. Results: The anti-p53 antibodies positive rate for patients with gastric carcinoma was increased (31.1%, 19/61) through the combination of p53-ELISA and phage-ELISA. We found that the positive anti-p53 antibodies correlated significantly with tumor size (P = 0.047). The combination of the anti-p53 antibodies and carcinoembryonic antigen could improve the diagnosis for patients with gastric carcinoma. Conclusions: This approach indicated an increased anti-p53 antibodies positive rate for patients with gastric carcinoma and provided a useful marker for clinical diagnosis for patients with gastric carcinoma.     

Environmental factors in relation to breast cancer characterized by p53 protein expression.

Findings from studies of cigarette smoking and low-dose ionizing radiation exposure and breast cancer are unclear. Laboratory studies indicate that both exposures can cause DNA damage, potentially increasing cancer risk if such mutations occur in growth control genes, such as p53. We examined the potential etiologic heterogeneity of breast cancer by evaluating whether associations between cigarette smoking and low-dose ionizing radiation and breast cancer differed by p53 protein expression status. Data were obtained from the Carolina Breast Cancer Study, a population-based, case-control study conducted among African-American and white women ages 20-74 years. Questionnaire data were available from 861 women with incident, primary invasive breast cancer and 790 community-based controls. p53 immunostaining was performed on tissue from 683 women with breast cancer; 46% were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (ORs) for p53+ and p53- breast cancer, as compared with controls, in relation to smoking and low-dose ionizing radiation exposure. Smoking was not differentially associated with p53+ or p53- breast cancer, even when duration, dose, and passive smoking status were considered. Exposure to individual sources of radiation did not differ for p53+ and p53- breast cancers. However, ORs for combined exposure to chest X-rays and occupational radiation were higher for p53+ [OR, 2.2; 95% confidence interval (CI), 1.0-5.3] than p53- breast cancer (OR, 1.2; 95% CI, 0.5-3.4). Combined exposure to radiation from other medical sources as well as occupational exposure was also higher for p53+ (OR, 3.7; 95% CI, 0.8-16.8) than for p53- breast cancer (OR, 1.7; 95% CI, 0.3-10.5). Although preliminary, our results suggest that exposure to multiple sources of low-dose ionizing radiation may contribute to the development of p53+ breast cancer.     

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

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 alpha-fetoprotein levels and clinicopathological characteristics 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.     

Autoantibodies against p53 are associated with chromosome 17p deletions in chronic lymphocytic leukemia

Autoantibodies against p53 have been observed in many cancers, often linked with abnormalities in the TP53 gene. Since p53 mutations and deletions at chromosome 17p are known to occur in CLL, we measured anti-p53 autoantibodies by ELISA in plasma samples from patients with normal cytogenetics as well as those with 13q, 11q, and 17p deletions as well as trisomy 12. Anti-p53 autoantibodies were detected in over half of the patients with a 17p deletion but in very few of the others. There was no correlation between the levels of anti-p53 antibodies and the percentage of cells with 17p abnormalities. The levels of the anti-p53 autoantibodies remained stable for most patients with serial samples. Increased levels of antibodies that bound to two peptide fragments of p53 were also seen in patients with 17p deletions. At least on case with high levels of anti-p53 autoantibodies had a heterozygotic mutation known to result in a dominant negative phenotype, suggesting that aberrant expression of p53 may contribute to the development of autoantibodies and suggests that these autoantibodies may reflect biological features relevant to prognosis.