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

Tang, Reiping; Ko, Miao-Chen; Wang, Jeng‐Yi; Changchien, Chung Rong; Chen, Hong Hwa; Chen, Jinn‐Shiun; Hsu, Kuan-Cheng; Chiang, Jy-Ming; Hsieh, Ling–Ling

doi:10.1002/ijc.1541

Cited by 59 publications

(52 citation statements)

References 31 publications

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“…In the present study, several factors, including depth of tumor invasion, lymph node metastasis, stage and CEA, were found to be significantly associated with positive Ap53Ab expression. The association between elevated Ap53Ab and lymph node metastasis was consistent with previous data from an Asian population (4,5,7). In gastric cancer, an elevated Ap53Ab level tended to be associated with lymph node metastasis (21), but positive Ap53Ab expression was not found to be correlated with lymph node metastasis in esophageal squamous cell carcinoma (22).…”

Section: Ap53ab Expression N (%) -----------------------------------supporting

confidence: 89%

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Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer

Kumamoto

Ishida

Kuwabara

et al. 2017

Molecular and Clinical Oncology

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Abstract. The aim of the present study was to investigate the usefulness of serum anti-p53 antibody (Ap53Ab) measurement for the diagnosis of colorectal cancer (CRC), and the clinical significance of the association between Ap53Ab expression and survival rate. Ap53Ab, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 were measured by ELISA in 674 CRC patients and 115 healthy volunteers (control group). The half-life time of Ap53Ab and CEA was calculated. The association between positive Ap53Ab expression and clinicopathological characteristics, including survival rate, was analyzed. Of the 674 CRC patients, 195 (28.9%) were positive for Ap53Ab expression, while the positive rates of CEA and CA19-9 level were 39.9 and 16.9%, respectively. Positivity for Ap53Ab alone was observed in 94 patients (13.9%), whereas the positivity rate of any markers examined was 58.7%. The mean half-life of Ap53Ab and CEA was 30.7 and 11.3 days, respectively. Positive expression of Ap53Ab was significantly associated with the depth of tumor invasion (P<0.001), lymph node metastasis (P=0.024), stage (P<0.001) and CEA level (P= 0.005). No significant correlation between Ap53Ab expression and poor survival rate was observed. The positive rate of Ap53Ab was higher compared with that of CEA and CA19-9 in early-stage CRC. The combination of these markers improved the diagnostic yield of CRC up to ~60%. Furthermore, Ap53Ab expression was associated with lymph node metastasis, but not with shorter survival. These results indicated that the measurement of Ap53Ab may contribute to increased rate of detection of CRC, particularly in patients with early-stage disease, in clinical practice.

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Section: Ap53ab Expression N (%) -----------------------------------supporting

confidence: 89%

“…Mutations of the TP53 gene, which were detected in half of CRC cases (6), were strongly associated with carcinogenesis. The accumulation of mutated-TP53 protein induces the synthesis of Ap53Ab, depending on the condition of the host immune system (7).…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer

Kumamoto

Ishida

Kuwabara

et al. 2017

Molecular and Clinical Oncology

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“…Autoantibodies observed in some tumors may be due to large tumor masses and necrosis exposing a large amount of autoantigen to the immune system. Alternatively, as suggested for p53, in which mutations have been found to be associated with more aggressive tumors and poorer prognosis of breast cancer, the mutated p53 tends to have a much longer half-life than the wild-type p53, leading to accumulation of the protein and anti-p53 Ab production (70,71). In contrast, the anti-actin Abs observed in MCB are probably a result of increased tumor cell apoptosis; thus, these Abs serve as a marker of a beneficial biologic process.…”

Section: Discussionmentioning

confidence: 99%

“…In breast cancer, particular interest in such correlations has focused on anti-53 autoantibodies, where some studies observed a correlation between poor prognosis and increased levels of anti-53 autoantibodies (70,71), although these results could not always be confirmed by others (72). It may, therefore, seem surprising that the favorable prognosis of MCB correlates with anti-actin autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

Hansen

Nielsen

Ditzel

2002

The Journal of Immunology

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Tumor-infiltrating lymphoplasmacytic cells are a key feature of medullary carcinoma of the breast (MCB), a distinct subtype of human breast cancer that, despite cytologically anaplastic characteristics, has a more favorable prognosis than other types of breast cancer. Since it has been proposed that the improved clinical outcome is due at least in part to the presence of a prominent lymphoplasmacytic cell infiltrate in the tumor stroma, we recently examined the tumor-infiltrating B cell response in MCB and showed that it is oligoclonal and directed against an intracellular protein translocated to the cell surface upon MCB cell apoptosis. Human Abs cloned from MCB lymphoplasmacytic infiltrate-derived phage display libraries and reflecting the dominant part of the response were used to identify the target Ag as actin. Here, we have characterized in detail the cloned human IgG Abs and the translocation process of actin to the cell surface of apoptotic MCB cells. Our analysis shows that the cloned Abs bind specifically and with high affinity to actin, as determined by ELISA and surface plasmon resonance. Sequence analysis revealed that the Abs are highly somatically mutated, with high replacement to silent ratios, indicative of an Ag-driven, affinity-matured response. Interestingly, the tumor-infiltrating B cells in half the MCB patients mainly exhibited an IgG2 response, while IgG1 dominated in the others. To gain insight to the molecular events that may elicit such an Ab response, we examined the translocation of actin to the cell surface of apoptotic MCB cells using flow cytometry and laser scanning cytometry. Our results show that actin becomes exposed on the cell surface of a large proportion of apoptotic MCB cells as an early apoptotic event. We propose that the Ab response against actin produced by tumor-infiltrating B lymphoplasmacytic cells is Ag-driven, affinity-matured, and elicited due to the increased rate of apoptosis occurring within the MCB tumor that facilitates the translocation and proteolytic fragmentation of intracellular proteins.

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“…Lechpammer et al (2004) in a series of 220 colorectal cancer patients detected p53-Ab mainly in Dukes' B and C stages. Moreover, Tang et al (2001), in a large study of 998 colorectal patients demonstrated that the presence of p53-Ab correlates with tumour progression in colorectal carcinogenesis and an increase with advanced node metastasis. However, in these studies, both colon and rectal cancers were analysed as a single entity, whereas our work was focalised only on rectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis

Lopez-Crapez

Bibeau²,

Thézenas³

et al. 2005

Br J Cancer

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The aim of this study was to evaluate, in a prospective study, the predictive role of p53 status analysed at four different levels in identifying the response to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70 patients were staged and endoscopic forceps biopsies from the tumour area were taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis, immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated after surgery by both pathologic downstaging and histologic tumour regression grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%); and p53 antibodies were detected in 11 patients (16.7%). In the multilevel analysis of p53 status, gene mutations correlated with both nuclear protein overexpression (Po0.0001) and loss of heterozygosity (P ¼ 0.013). In all, 29 patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%) were classified as tumour regression grade 1. Whatever the method of evaluation of treatment response, no correlation between p53 alterations and response to radiotherapy was observed. Our results do not support the use of p53 alterations alone as a predictive marker for response to radiotherapy in rectal carcinoma.

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

Cited by 59 publications

References 31 publications

Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer

Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis

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