Skip to main content
Top
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Serum p53 antibody detection in patients with impaired lung function

Authors: Manlio Mattioni, Patrizia Chinzari, Silvia Soddu, Lidia Strigari, Vincenzo Cilenti, Eliuccia Mastropasqua

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 overexpression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with Chronic Obstructive Pulmonary Disease, before the diagnosis of lung and other tobacco-related tumors.

Methods

A large prospective study was carried out, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. The p53Ab levels were evaluated by a specific ELISA in 675 subjects.

Results

Data showed that significant levels of serum p53Abs were present in 35 subjects (5.2%); no difference was observed in the presence of p53Abs with regard to age and gender, while p53Abs correlated with the number of cigarettes smoked per day and packs-year. Furthermore, serum p53Abs were associated with the worst lung function impairment. The median p53Ab level in positive subjects was 3.5 units/ml (range 1.2 to 65.3 units/ml). Only fifteen positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients.

Conclusion

The presence of serum p53Abs was found to be associated with smoking level and lung function impairment, both risk factors of cancer development. However, in our study we have not observed the occurrence of lung cancer or other cancers in the follow-up of positive subjects, therefore we cannot directly correlate the presence of serum p53Abs with cancer risk.
Literature
1.
go back to reference Walser T, Cui X, Yanagawa J, Lee JM, Heinrich E, Lee G, Sharma S, Dubinett SM: Smoking and lung cancer. The role of inflammation. Proc Am Thorac Soc. 2008, 5: 811-815.CrossRefPubMedPubMedCentral Walser T, Cui X, Yanagawa J, Lee JM, Heinrich E, Lee G, Sharma S, Dubinett SM: Smoking and lung cancer. The role of inflammation. Proc Am Thorac Soc. 2008, 5: 811-815.CrossRefPubMedPubMedCentral
2.
go back to reference Soussi T: p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000, 60: 1777-1788.PubMed Soussi T: p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000, 60: 1777-1788.PubMed
3.
go back to reference Hill KA, Sommer SS: p53 as a mutagen test in breast cancer. Environ Mol Mutagen. 2002, 39: 216-227.CrossRefPubMed Hill KA, Sommer SS: p53 as a mutagen test in breast cancer. Environ Mol Mutagen. 2002, 39: 216-227.CrossRefPubMed
4.
go back to reference Dowing SR, Russell PJ, Jackson P: Alterations in p53 are common in early stage prostate cancer. Can J Urol. 2003, 10: 1924-1933. Dowing SR, Russell PJ, Jackson P: Alterations in p53 are common in early stage prostate cancer. Can J Urol. 2003, 10: 1924-1933.
5.
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: 111-115.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: 111-115.CrossRefPubMed
6.
go back to reference Cawley HM, Meltzer SJ, De Benedetti VM, Hollstein MC, Muehlbauer KR, Liang L, Bennett WP, Souza RF, Greenwald BD, Cottrell J, Salabes A, Bartsch H, Trivers GE: Anti-p53 antibodies in patients with Barrett’s esophagus or esophageal carcinoma can predate cancer diagnosis. Gastroenterology. 1998, 115: 19-27.CrossRefPubMed Cawley HM, Meltzer SJ, De Benedetti VM, Hollstein MC, Muehlbauer KR, Liang L, Bennett WP, Souza RF, Greenwald BD, Cottrell J, Salabes A, Bartsch H, Trivers GE: Anti-p53 antibodies in patients with Barrett’s esophagus or esophageal carcinoma can predate cancer diagnosis. Gastroenterology. 1998, 115: 19-27.CrossRefPubMed
7.
go back to reference Yoshizawa S, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Mukai M, Fujita T, Kawakami Y, Hibi T: Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis. Inflamm Bowel Dis. 2007, 13: 865-873.CrossRefPubMed Yoshizawa S, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Mukai M, Fujita T, Kawakami Y, Hibi T: Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis. Inflamm Bowel Dis. 2007, 13: 865-873.CrossRefPubMed
8.
go back to reference Li Y, Karjalainen A, Koskinen H, Hemminki K, Vainio H, Shnaidman M, Ying Z, Pukkala E, Brandt-Rauf PW: p53 autoantibodies predict subsequent development of cancer. Int J Cancer. 2005, 114: 157-160.CrossRefPubMed Li Y, Karjalainen A, Koskinen H, Hemminki K, Vainio H, Shnaidman M, Ying Z, Pukkala E, Brandt-Rauf PW: p53 autoantibodies predict subsequent development of cancer. Int J Cancer. 2005, 114: 157-160.CrossRefPubMed
9.
go back to reference Martin B, Verdebout JM, Mascaux C, Paesmans M, Rouas G, Verhest A, Ninane V, Sculier JP: Expression of p53 in preneoplastic and early neoplastic bronchial lesions. Oncol Rep. 2002, 9: 223-229.PubMed Martin B, Verdebout JM, Mascaux C, Paesmans M, Rouas G, Verhest A, Ninane V, Sculier JP: Expression of p53 in preneoplastic and early neoplastic bronchial lesions. Oncol Rep. 2002, 9: 223-229.PubMed
10.
go back to reference Lubin R, Zalcman G, Bouchet L, Trédanel J, Legros Y, Cazals D, Hirsch A, Soussi T: Serum p53 antibodies as early markers of lung cancer. Nat Med. 1995, 1: 701-702.CrossRefPubMed Lubin R, Zalcman G, Bouchet L, Trédanel J, Legros Y, Cazals D, Hirsch A, Soussi T: Serum p53 antibodies as early markers of lung cancer. Nat Med. 1995, 1: 701-702.CrossRefPubMed
11.
go back to reference Trivers GE, De Benedetti VM, Cawley HL, Caron G, Harrington AM, Bennett WP, Jett JR, Colby TV, Tazelaar H, Pairolero P, Miller RD, Harris CC: Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. Clin Cancer Res. 1996, 2: 1767-1775.PubMed Trivers GE, De Benedetti VM, Cawley HL, Caron G, Harrington AM, Bennett WP, Jett JR, Colby TV, Tazelaar H, Pairolero P, Miller RD, Harris CC: Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. Clin Cancer Res. 1996, 2: 1767-1775.PubMed
12.
go back to reference Youlden DR, Cramb SM, Baade PD: The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008, 3: 819-831.CrossRefPubMed Youlden DR, Cramb SM, Baade PD: The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008, 3: 819-831.CrossRefPubMed
13.
go back to reference Hecht SS: Progress and challenges in selected areas of tobacco carcinogenesis. Chem Res Toxicol. 2008, 21: 160-171.CrossRefPubMed Hecht SS: Progress and challenges in selected areas of tobacco carcinogenesis. Chem Res Toxicol. 2008, 21: 160-171.CrossRefPubMed
14.
go back to reference Wasswa-Kintu S, Gan WQ, Man SF, Pare PD, Sin DD: Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax. 2005, 60: 570-575.CrossRefPubMedPubMedCentral Wasswa-Kintu S, Gan WQ, Man SF, Pare PD, Sin DD: Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax. 2005, 60: 570-575.CrossRefPubMedPubMedCentral
15.
go back to reference Loganathan RS, Stover DE, Shi W, Venkatraman E: Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer. Chest. 2006, 129: 1305-1312.CrossRefPubMed Loganathan RS, Stover DE, Shi W, Venkatraman E: Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer. Chest. 2006, 129: 1305-1312.CrossRefPubMed
16.
go back to reference Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, Calia N, Petruzzelli S, Corbetta L, Cavallesco G, Forini E, Saetta M, Ciaccia A, Fabbri LM: COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004, 59: 679-681.CrossRefPubMedPubMedCentral Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, Calia N, Petruzzelli S, Corbetta L, Cavallesco G, Forini E, Saetta M, Ciaccia A, Fabbri LM: COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004, 59: 679-681.CrossRefPubMedPubMedCentral
17.
go back to reference Engels EA: Inflammation in the development of lung cancer: epidemiological evidence. Expert Rev Anticancer Ther. 2008, 8: 605-615.CrossRefPubMed Engels EA: Inflammation in the development of lung cancer: epidemiological evidence. Expert Rev Anticancer Ther. 2008, 8: 605-615.CrossRefPubMed
18.
go back to reference Brower V: Feeding the flame: new research adds to role of inflammation in cancer development. J Natl Cancer Inst. 2005, 97: 251-253.CrossRefPubMed Brower V: Feeding the flame: new research adds to role of inflammation in cancer development. J Natl Cancer Inst. 2005, 97: 251-253.CrossRefPubMed
19.
go back to reference Komarova EA, Krivokrysenko V, Wang K, Neznanov N, Chernov MV, Komarov PG, Brennan ML, Golovkina TV, Rokhlin OW, Kuprash DV, Nedospasov SA, Hazen SL, Feinstein E, Gudkov AV: p53 is a suppressor of inflammatory response in mice. FASEB J. 2005, 19: 1030-1032.PubMed Komarova EA, Krivokrysenko V, Wang K, Neznanov N, Chernov MV, Komarov PG, Brennan ML, Golovkina TV, Rokhlin OW, Kuprash DV, Nedospasov SA, Hazen SL, Feinstein E, Gudkov AV: p53 is a suppressor of inflammatory response in mice. FASEB J. 2005, 19: 1030-1032.PubMed
20.
go back to reference Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ: Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem. 1999, 274: 10911-10915.CrossRefPubMed Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ: Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem. 1999, 274: 10911-10915.CrossRefPubMed
21.
go back to reference Richardson CM, Sharma RA, Cox G, O'Byrne KJ: Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: potential targets for chemoprevention and systemic therapy. Lung Cancer. 2003, 39: 1-13.CrossRefPubMed Richardson CM, Sharma RA, Cox G, O'Byrne KJ: Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: potential targets for chemoprevention and systemic therapy. Lung Cancer. 2003, 39: 1-13.CrossRefPubMed
22.
go back to reference Wistuba II, Mao L, Gazdar AF: Smoking molecular damage in bronchial epithelium. Oncogene. 2002, 21: 7298-7306.CrossRefPubMed Wistuba II, Mao L, Gazdar AF: Smoking molecular damage in bronchial epithelium. Oncogene. 2002, 21: 7298-7306.CrossRefPubMed
23.
go back to reference Purdue MP, Gold L, Järvholm B, Alavanja MC, Ward MH, Vermeulen R: Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers. Thorax. 2007, 62: 51-56.CrossRefPubMed Purdue MP, Gold L, Järvholm B, Alavanja MC, Ward MH, Vermeulen R: Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers. Thorax. 2007, 62: 51-56.CrossRefPubMed
24.
go back to reference Cioffi M, Riegler G, Vietri MT, Pilla P, Caserta L, Carratù R, Sica V, Molinari AM: Serum p53 antibodies in patients affected with ulcerative colitis. Inflamm Bowel Dis. 2004, 10: 606-611.CrossRefPubMed Cioffi M, Riegler G, Vietri MT, Pilla P, Caserta L, Carratù R, Sica V, Molinari AM: Serum p53 antibodies in patients affected with ulcerative colitis. Inflamm Bowel Dis. 2004, 10: 606-611.CrossRefPubMed
25.
go back to reference Agaylan A, Binder D, Sauer M, Neuweiler H, Meyer O, Kiesewetter H, Salama A: A highly sensitive particle agglutination assay for the detection of p53 autoantibodies in patients with lung cancer. Cancer. 2007, 110: 2502-2506.CrossRefPubMed Agaylan A, Binder D, Sauer M, Neuweiler H, Meyer O, Kiesewetter H, Salama A: A highly sensitive particle agglutination assay for the detection of p53 autoantibodies in patients with lung cancer. Cancer. 2007, 110: 2502-2506.CrossRefPubMed
26.
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: 1570-1575.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: 1570-1575.CrossRefPubMed
27.
28.
29.
go back to reference Li Y, Brandt-Rauf PW, Carney WP, Tenney DY, Ford JG: Circulating anti-p53 antibodies in lung cancer and relationship to histology and smoking. Biomarkers. 1999, 4: 381-390.CrossRef Li Y, Brandt-Rauf PW, Carney WP, Tenney DY, Ford JG: Circulating anti-p53 antibodies in lung cancer and relationship to histology and smoking. Biomarkers. 1999, 4: 381-390.CrossRef
30.
go back to reference Pascual RM, Peters SP: Airway remodelling contributes to the progressive loss of lung function in asthma: an overview. J Allergy Clin Immunol. 2005, 116: 477-486.CrossRefPubMed Pascual RM, Peters SP: Airway remodelling contributes to the progressive loss of lung function in asthma: an overview. J Allergy Clin Immunol. 2005, 116: 477-486.CrossRefPubMed
31.
go back to reference Moss SF, Blaser MJ: Mechanisms of disease: inflammation and the origins of cancer. Nat Clin Pract Oncol. 2005, 2: 90-97.CrossRefPubMed Moss SF, Blaser MJ: Mechanisms of disease: inflammation and the origins of cancer. Nat Clin Pract Oncol. 2005, 2: 90-97.CrossRefPubMed
32.
go back to reference Mulcahy HE, Lyautey J, Lederrey C, Chen X, Anker P, Alstead EM, Ballinger A, Farthing MJ, Stroun M: A prospective study of K-ras mutations in the plasma of pancreatic cancer patients. Clin Cancer Res. 1998, 4: 271-275.PubMed Mulcahy HE, Lyautey J, Lederrey C, Chen X, Anker P, Alstead EM, Ballinger A, Farthing MJ, Stroun M: A prospective study of K-ras mutations in the plasma of pancreatic cancer patients. Clin Cancer Res. 1998, 4: 271-275.PubMed
33.
go back to reference Partanen R, Hemminki K, Koskinen H, Luo JC, Carney WP, Brand-Rauf PW: The detection of increased amounts of the extracellular domain of the epidermal growth factor receptor in serum during carcinogenesis in asbestosis patients. J Occup Med. 1994, 36: 1324-1328.CrossRefPubMed Partanen R, Hemminki K, Koskinen H, Luo JC, Carney WP, Brand-Rauf PW: The detection of increased amounts of the extracellular domain of the epidermal growth factor receptor in serum during carcinogenesis in asbestosis patients. J Occup Med. 1994, 36: 1324-1328.CrossRefPubMed
34.
go back to reference Cockayne DA, Cheng DT, Waschki B, Sridhar S, Ravindran P, Hilton H, Kourteva G, Bitter H, Pillai SG, Visvanathan S, Muller K-C, Holz O, Magnussen H, Watz H, Fine JS: Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity. PLoS ONE. 2012, 7: e38629-10.1371.CrossRefPubMedPubMedCentral Cockayne DA, Cheng DT, Waschki B, Sridhar S, Ravindran P, Hilton H, Kourteva G, Bitter H, Pillai SG, Visvanathan S, Muller K-C, Holz O, Magnussen H, Watz H, Fine JS: Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity. PLoS ONE. 2012, 7: e38629-10.1371.CrossRefPubMedPubMedCentral
Metadata
Title
Serum p53 antibody detection in patients with impaired lung function
Authors
Manlio Mattioni
Patrizia Chinzari
Silvia Soddu
Lidia Strigari
Vincenzo Cilenti
Eliuccia Mastropasqua
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-62

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine