P53 autoantibodies in 1006 patients followed up for breast cancer

Metcalfe, Su; Wheeler, T.K.; Picken, S.; Negus, S; Milner, A

doi:10.1186/bcr91

Cited by 35 publications

(29 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 75%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 75%

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

View full text Add to dashboard Cite

show abstract

“…Thus, in certain patients, an ongoing stimulus might trigger a progressive immune response over time. Although this effect might be counteracted by immunosuppression as a side effect of chemotherapy [24, 31], our results render it likely that the increased prevalence of confirmed anti-p53 positives in advanced stages of breast cancer mirrors the development of anti-p53 titers during the course of disease.…”

Section: Discussionmentioning

confidence: 85%

“…Thus, we do not assume that this marker will be clinically useful in identifying high-risk patients. Furthermore, a recently published follow-up study [31]with a similarly low overall incidence of anti-p53 autoantibodies (15%) in breast cancer, failed to show an association with the stage of the disease, and revealed a high stability of the anti-p53 status in the follow-up of a single patient. In view of the accepted prognostic value of aberrant p53 [8, 9]and the link between aberrant p53 and the development of anti-p53 [24], one would expect higher rates of p53 accumulation and consecutively anti-p53 positivity in recurrent disease.…”

Section: Discussionmentioning

confidence: 99%

Anti-p53 in Breast Cancer: Concordance of Different Assay Procedures and Association with p53 Antigen Expression

et al. 2002

View full text Add to dashboard Cite

Objective: Anti-p53 levels detected by different methods were compared in a predefined group of patients with breast cancer and correlated with p53 antigen expression in the corresponding tumors. Methods: P53 autoantibodies were investigated in 165 patients with primary breast cancer using ELISAs with recombinant or native p53. Immunoblot and indirect immunofluorescence (Huh7) were used for confirmation, p53 antigen expression in the tumor was determined immunohistochemically. Results: Using ELISA, overall 18/165 positives (11%) were detected, with only partly concordant results between the assays. Five positive sera were confirmed by immunoblot, and three also by indirect immunofluorescence. Anti-p53-positive patients detected by more than two assays showed accumulated p53 in the tumor (6/6) and mostly suffered from recurrent tumors (4/6; p = 0.02). In these cases, a trend towards a shortened disease-free interval was found (26 vs. 49 months; n.s.). In patients with a positive or borderline result in only one of the serological methods, there was no increased rate of p53 accumulation compared to anti-p53-negative patients (4/19 versus 35/126). Conclusions: Lack of assay standardization may partly explain the divergence in reports on anti-p53 and its clinicopathological associations. We speculate that, in different groups of patients, anti-p53 might be induced by different mechanisms.

show abstract

“…Most notably, autoantibodies directed against p53 correlate with poor prognosis. [19][20][21] Likewise, autoantibodies associated with paraneoplastic syndromes have been correlated with poor prognosis and are thought to lead to fatal neurologic disorders. 22,23 Autoantibodies correlated with prolonged survival of tumor patients are rare and to the best of our knowledge of low specificity.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

Pallasch

Struss

Munnia

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma‐expressed antigens including GLEA1, GLEA2 and PHD‐finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1‐autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma‐associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma. © 2005 Wiley‐Liss, Inc.

show abstract

P53 autoantibodies in 1006 patients followed up for breast cancer

Cited by 35 publications

References 10 publications

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

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

Anti-p53 in Breast Cancer: Concordance of Different Assay Procedures and Association with p53 Antigen Expression

Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

Contact Info

Product

Resources

About