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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Prognostic role of serum p53 antibodies in lung cancer

Authors: Manlio Mattioni, Silvia Soddu, Andrea Prodosmo, Paolo Visca, Salvatore Conti, Gabriele Alessandrini, Francesco Facciolo, Lidia Strigari

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Mutations in the TP53 (Tumour Protein 53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in cancer patients. Our aim was to evaluate the presence and prognostic role of these antibodies in lung cancer patients and to investigate whether they were related to p53 expression or TP53 mutations in tumour tissues.

Methods

A total of 201 lung cancer patients were evaluated for p53 antibodies by ELISA (Enzyme-Linked Immunosorbent Assay) and control was obtained from 54 patients with non-malignant disorders; p53 expression was evaluated in 131 of the lung cancer patients by immunohistochemistry and TP53 mutations were then investigated in 53 tumours positively staining for p53 and in 12 tumours without p53 overexpression, whose DNA was available for direct sequencing.

Results

Our results show that 20.4% of cancer patients have positive levels of p53 antibodies, while none of the controls resulted positive. High levels of p53 expression are detected in 57.3% of cases and a significant correlation between serum p53 antibodies and high levels of p53 expression in the corresponding tumours is observed. In non-small cell lung cancer, p53 antibodies are significantly associated with poorly differentiated tumours; furthermore, high levels of p53 expression significantly correlated with squamous cell carcinoma and tumours with highest grade. Survival time of non-small cell lung cancer patients low/negative for serum p53 antibodies was significantly longer compared to patients with positive levels (p = 0.049); in particular, patients with squamous cell carcinoma, but not adenocarcinoma, low/negative for these antibodies show a significant better survival compared to serum-positive patients (p = 0.044).

Conclusions

In our study, detection of serum p53 antibodies in non-small cell lung cancer patients has been shown to be useful in identifying subsets of patients with poor prognosis. A significant correlation between the presence of serum p53 antibodies in lung cancer patients and p53 overexpression in the corresponding tumours was also observed. We did not find a significant correlation between levels of serum p53 antibodies and TP53 mutations in the corresponding tumours.
Literature
1.
go back to reference World Cancer Report 2014. Cancer worldwide: pages 16-53. In: Stewart BW, Wild CP, editors. Lyon, France: International Agency for Research on Cancer; 2014. World Cancer Report 2014. Cancer worldwide: pages 16-53. In: Stewart BW, Wild CP, editors. Lyon, France: International Agency for Research on Cancer; 2014.
2.
3.
go back to reference Soussi T. p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000;60:1777–88.PubMed Soussi T. p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000;60:1777–88.PubMed
4.
go back to reference Gao RJ, Bao HZ, Yang Q, Cong Q, Song JN, Wang L. The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. Breast Cancer Res Treat. 2005;93:111–5.CrossRefPubMed Gao RJ, Bao HZ, Yang Q, Cong Q, Song JN, Wang L. The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. Breast Cancer Res Treat. 2005;93:111–5.CrossRefPubMed
5.
go back to reference Lubin R, Zalcman G, Bouchet L, Trédaniel J, Legros Y, Cazals D, et al. Serum p53 antibodies as early markers of lung cancer. Nat Med. 1995;1:701–2.CrossRefPubMed Lubin R, Zalcman G, Bouchet L, Trédaniel J, Legros Y, Cazals D, et al. Serum p53 antibodies as early markers of lung cancer. Nat Med. 1995;1:701–2.CrossRefPubMed
6.
go back to reference Zhang J, Xu Z, Yu L, Chen M, Li K. Assessment of the potential diagnostic value of serum p53 antibody for cancer: a meta-analysis. PLoS One. 2014;9:e99255.CrossRefPubMedPubMedCentral Zhang J, Xu Z, Yu L, Chen M, Li K. Assessment of the potential diagnostic value of serum p53 antibody for cancer: a meta-analysis. PLoS One. 2014;9:e99255.CrossRefPubMedPubMedCentral
7.
go back to reference Lei Q-Q, Liu J-W, Zheng H. Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a bivariate meta-analysis. Eur Rev Med Pharmacol Sci. 2013;17:3012–8.PubMed Lei Q-Q, Liu J-W, Zheng H. Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a bivariate meta-analysis. Eur Rev Med Pharmacol Sci. 2013;17:3012–8.PubMed
8.
go back to reference Park Y, Kim Y, Lee J-H, Lee EY, Kim H-S. Usefulness of serum anti-p53 antibody assay for lung cancer diagnosis. Arch Pathol Lab Med. 2011;135:1570–5.CrossRefPubMed Park Y, Kim Y, Lee J-H, Lee EY, Kim H-S. Usefulness of serum anti-p53 antibody assay for lung cancer diagnosis. Arch Pathol Lab Med. 2011;135:1570–5.CrossRefPubMed
9.
go back to reference Yu D-H, Li J-H, Wang Y-C, Xu J-G, Pan P-T, Wang L. Serum anti-p53 antibody detection in carcinomas and the predictive values of serum p53 antibodies, carcino-embryonic antigen and carbohydrate antigen 12–5 in the neoadjuvant chemotherapy treatment for III stage non-small cell lung cancer patients. Clin Chim Acta. 2011;412:930–5.CrossRefPubMed Yu D-H, Li J-H, Wang Y-C, Xu J-G, Pan P-T, Wang L. Serum anti-p53 antibody detection in carcinomas and the predictive values of serum p53 antibodies, carcino-embryonic antigen and carbohydrate antigen 12–5 in the neoadjuvant chemotherapy treatment for III stage non-small cell lung cancer patients. Clin Chim Acta. 2011;412:930–5.CrossRefPubMed
10.
go back to reference Kumar S, Mohan A, Guleria R. Prognostic implications of circulating anti-p53 antibodies in lung cancer - a review. Eur J Cancer Care. 2009;18:248–54.CrossRef Kumar S, Mohan A, Guleria R. Prognostic implications of circulating anti-p53 antibodies in lung cancer - a review. Eur J Cancer Care. 2009;18:248–54.CrossRef
11.
go back to reference Cioffi M, Riegler G, Vietri MT, Pilla P, Caserta L, Carratù R, et al. Serum p53 antibodies in patients affected with ulcerative colitis. Inflamm Bowel Dis. 2004;10:606–11.CrossRefPubMed Cioffi M, Riegler G, Vietri MT, Pilla P, Caserta L, Carratù R, et al. Serum p53 antibodies in patients affected with ulcerative colitis. Inflamm Bowel Dis. 2004;10:606–11.CrossRefPubMed
12.
13.
go back to reference Sangrajrang S, Sornprom A, Chernrungroj G, Soussi T. Serum p53 antibodies in patients with lung cancer: correlation with clinicopathologic features and smoking. Lung Cancer. 2003;39:297–301.CrossRefPubMed Sangrajrang S, Sornprom A, Chernrungroj G, Soussi T. Serum p53 antibodies in patients with lung cancer: correlation with clinicopathologic features and smoking. Lung Cancer. 2003;39:297–301.CrossRefPubMed
14.
go back to reference Cioffi M, Vietri MT, Gazzerro P, Magnetta R, D’Auria A, Durante A, et al. Serum anti-p53 antibodies in lung cancer: comparison with established tumor markers. Lung Cancer. 2001;33:163–9.CrossRefPubMed Cioffi M, Vietri MT, Gazzerro P, Magnetta R, D’Auria A, Durante A, et al. Serum anti-p53 antibodies in lung cancer: comparison with established tumor markers. Lung Cancer. 2001;33:163–9.CrossRefPubMed
15.
go back to reference Laudanski J, Niklinska W, Burzykowski T, Chyczewski L, Niklinski J. Prognostic significance of p53 and bcl-2 abnormalities in operable non small cell lung cancer. Eur Respir J. 2001;17:660–6.CrossRefPubMed Laudanski J, Niklinska W, Burzykowski T, Chyczewski L, Niklinski J. Prognostic significance of p53 and bcl-2 abnormalities in operable non small cell lung cancer. Eur Respir J. 2001;17:660–6.CrossRefPubMed
16.
go back to reference Rybárová S, Hodorová I, Muri J, Mihalik J, Adamkov M, Svajdler M, et al. Prognostic significance of p53 protein and X-ray repair cross-complementing protein 1 in non-small cell lung cancer. Tumori. 2011;97:79–85.PubMed Rybárová S, Hodorová I, Muri J, Mihalik J, Adamkov M, Svajdler M, et al. Prognostic significance of p53 protein and X-ray repair cross-complementing protein 1 in non-small cell lung cancer. Tumori. 2011;97:79–85.PubMed
17.
go back to reference Wang Y-C, Lin R-K, Tan Y-H, Chen J-T, Chen C-Y, Wang Y-C. Wild-type p53 overexpression and its correlation with MDM2 and p14ARF alterations: an alternative pathway to non-small-cell lung cancer. J Clin Oncol. 2005;23:154–64.CrossRefPubMed Wang Y-C, Lin R-K, Tan Y-H, Chen J-T, Chen C-Y, Wang Y-C. Wild-type p53 overexpression and its correlation with MDM2 and p14ARF alterations: an alternative pathway to non-small-cell lung cancer. J Clin Oncol. 2005;23:154–64.CrossRefPubMed
18.
go back to reference Mack U, Ukena D, Montenarh M, Sybrecht GW. Serum anti-p53 antibodies in patients with lung cancer. Oncol Rep. 2000;7:669–74.PubMed Mack U, Ukena D, Montenarh M, Sybrecht GW. Serum anti-p53 antibodies in patients with lung cancer. Oncol Rep. 2000;7:669–74.PubMed
19.
go back to reference Bergqvist M, Brattström D, Larsson A, Hesselius P, Brodin O, Wagenius G. The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival. BMC Cancer. 2004;4:66.CrossRefPubMedPubMedCentral Bergqvist M, Brattström D, Larsson A, Hesselius P, Brodin O, Wagenius G. The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival. BMC Cancer. 2004;4:66.CrossRefPubMedPubMedCentral
20.
go back to reference Hashim M, Sayed M, Samy N, Elshazly S. Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer. Med Oncol. 2011;28:322–30.CrossRefPubMed Hashim M, Sayed M, Samy N, Elshazly S. Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer. Med Oncol. 2011;28:322–30.CrossRefPubMed
21.
go back to reference Bergqvist M, Brattström D, Lamberg K, Hesselius P, Wernlund J, Larsson A, et al. The presence of anti-p53 antibodies in sera prior to thoracic surgery in non small cell lung cancer patients: its implications on tumor volume, nodal involvement, and survival. Neoplasia. 2003;5:283–7.CrossRefPubMedPubMedCentral Bergqvist M, Brattström D, Lamberg K, Hesselius P, Wernlund J, Larsson A, et al. The presence of anti-p53 antibodies in sera prior to thoracic surgery in non small cell lung cancer patients: its implications on tumor volume, nodal involvement, and survival. Neoplasia. 2003;5:283–7.CrossRefPubMedPubMedCentral
22.
go back to reference Neri M, Betta P, Marroni P, Filiberti R, Cafferata M, Mereu C, et al. Serum anti-p53 autoantibodies in pleural malignant mesothelioma, lung cancer and non-neoplastic lung diseases. Lung Cancer. 2003;39:165–72.CrossRefPubMed Neri M, Betta P, Marroni P, Filiberti R, Cafferata M, Mereu C, et al. Serum anti-p53 autoantibodies in pleural malignant mesothelioma, lung cancer and non-neoplastic lung diseases. Lung Cancer. 2003;39:165–72.CrossRefPubMed
23.
go back to reference Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutations. Cancer Res. 1992;52:4168–74.PubMed Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutations. Cancer Res. 1992;52:4168–74.PubMed
24.
go back to reference Tsao MS, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, et al. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non-small cell lung cancer. J Clin Oncol. 2007;25:5240–7.CrossRefPubMed Tsao MS, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, et al. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non-small cell lung cancer. J Clin Oncol. 2007;25:5240–7.CrossRefPubMed
25.
go back to reference Groeger AM, Esposito V, De Luca A, Cassandro R, Tonini G, Ambrogi V, et al. Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small cell lung cancers. Histopathology. 2004;44:54–63.CrossRefPubMed Groeger AM, Esposito V, De Luca A, Cassandro R, Tonini G, Ambrogi V, et al. Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small cell lung cancers. Histopathology. 2004;44:54–63.CrossRefPubMed
26.
go back to reference Huncharek M, Kupelnick B, Geschwind JF, Caubet JF. Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies. Cancer Lett. 2000;153:219–26.CrossRefPubMed Huncharek M, Kupelnick B, Geschwind JF, Caubet JF. Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies. Cancer Lett. 2000;153:219–26.CrossRefPubMed
Metadata
Title
Prognostic role of serum p53 antibodies in lung cancer
Authors
Manlio Mattioni
Silvia Soddu
Andrea Prodosmo
Paolo Visca
Salvatore Conti
Gabriele Alessandrini
Francesco Facciolo
Lidia Strigari
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1174-4

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