Abstract
Serum p53 antibodies have been shown to be a poor prognostic marker in resected non-small-cell lung cancer (NSCLC), but studies in small-cell lung cancer (SCLC) have been contradictory. We have studied the incidence of p53 antibodies in a large SCLC cohort treated at one oncology centre and correlated the results with survival. 231 patients (63% male, median age 65), diagnosed and treated for SCLC between 1987 and 1994 at The Royal Marsden Hospital NHS Trust, had sera stored pretreatment. All samples were tested for p53 antibodies (p53-Ab) using a standardized ELISA technique with a selection of strongly ELISA positive, weakly ELISA positive and negative samples being confirmed with immunoprecipitation. 54 patients were positive for p53-Ab (23%). The presence of a high titre of p53-Ab (titre ratio >5) appears to be associated with a survival advantage with a relative risk of death of 1.71 (95% CI: 1.14–2.58) in those without the antibody (P = 0.02). This study, the largest homogenous group so far looking at p53-Ab in SCLC, suggests that p53 antibody detection may have a role in predicting outcome in this type of cancer. © 2000 Cancer Research Campaign http://www.bjcancer.com
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References
Angelopoulou K, Diamandis EP, Sutherland DJ, Kellen JA and Bunting PS (1994 Prevalence of serum antibodies against the p53 tumour suppressor gene protein in various cancers. Int J Cancer 58: 480–487
Bergqvist M, Brattstrom D, Larsson A, Holmertz J, Hesselius P, Rosenberg L, Wagenius G and Brodin O (1998 P53 auto-antibodies in non-small cell lung cancer patients can predict increased life expectancy after radiotherapy. Anticancer Res 18: 1999–2002
Bourhis J, Lubin R, Roche B, Koscielny S, Bosq J, Dubois I, Talbot M, Marandas P, Schwaab G, Wibault P, Luboinski B, Eschwege F and Soussi T (1996 Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst 88: 1228–1233
Cote RJ, Esrig D, Groshen S, Jones PA and Skinner DG (1997 p53 and treatment of bladder cancer (letter, comment). Nature 385: 123–124
Cox DR (1972 Regression models and life tables. Royal Stat Soc (B) 34: 187–220
D’Amico D, Carbone D, Mitsudomi T, Nau M, Fedorko J, Russell E, Johnson B, Buchhagen D, Bodner S, Phelps R, Gazdar A and Minna JD (1992 High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumours. Oncogene 7: 339–346
Davidoff AM, Iglehart JD and Marks JR (1992 Immune response to p53 is dependent upon p53/hsp70 complexes in breast cancers. Proc Natl Acad Sci 89: 3439–3442
Einhorn LH, Crawford J, Birch R, Omura G, Johnson DH and Greco FA (1988 Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer. Journal of Clinical Oncology 6, 3451–456
Fritsche M, Haessler C and Brandner G (1993 Induction of nuclear accumulation of the tumour-suppressor protein p53 by DNA-damaging agents. Oncogene 8: 307–318
Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M and Suemasu K (1991 Randomised trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst 83: 855–861
Girling DJ (1996 Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Party. Lancet 348, 9027563–566
Harpole DH Jr, Herndon JE 2nd, Wolfe WG, Iglehart JD and Marks JR (1995 A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology and oncoprotein expression. Cancer Res 55: 51–56
Houbiers JGA, Vanderburg SH, Vandewatering LMG, Tollenaar RAEM, Brand A, Vandevelde CJH and Melief CJM (1995 Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer 72: 637–641
Iizasa T, Fujisawa T, Saitoh Y, Hiroshima K and Ohwada H (1998 Serum anti-p53 autoantibodies in primary resected non-small-cell lung carcinoma. Cancer Immunol Immunother 46: 345–349
Kirsch DG and Kastan MB (1998 Tumor-suppressor p53: Implications for tumor development and prognosis. J Clin Oncol 16: 3158–3168
Komiya T, Hirashima T, Takada N, Masuda N, Yasumitsu T, Nakagawa K, Hosono Y, Kikui M, Tsuji S, Fukuoka M and Kawase I (1997 Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung. Anticancer Res 17: 3721–3724
Kressner U, Glimelius B, Bergstrom R, Pahlman L, Larsson A and Lindmark G (1998 Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer. Brit J Cancer 77: 1848–1851
Laudanski J, Burzykowski T, Niklinska W, Chyczewski L, Furman M and Niklinski J (1998 Prognostic value of serum p53 antibodies in patients with resected non-small cell lung cancer. Lung Cancer 22: 191–200
Lee JS, Yoon A, Kalapurakal SK, Ro JY, Lee JJ, Tu N, Hittelman WN and Hong WK (1995 Expression of p53 oncoprotein in non-small cell lung cancer: A favourable prognostic factor. J Clin Oncol 13: 1893–1903
Lenner P, Wiklund F, Emdin SO, Arnerlov C, Eklund C, Hallmans G, Zentgraf H and Dillner J (1999 Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study. Brit J Cancer 79: 927–932
Levine AJ and Perry ME (1994 The 1993 Walter Hubert lecture: The role of p53 tumour suppressor gene in tumourgenesis. Br J Cancer 69: 409–416
Lubin R, Schlichtholz B, Bengoufa D, Zalcman G, Tredaniel J, Hirsch A, Caron de Fromentel C, Preudhomme C, Fenaux P, Fournier G, Mangin P, Laurent-Puig P, Pelletier G, Schlumberger M, Desgrandchamps F, Leduc A, Peyrat JP, Janin N, Bressac B and Soussi T (1993 Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53 – distribution on primary structure and exposure on protein surface. Cancer Res 53: 5872–5876
Lubin R, Schlichtholz B, Teillaurd JL, Dubois I, Bengoufa D and Soussi T (1995a P53 antibodies in patients with various types of cancer: assay, identification and characterisation. Clin Cancer Res 1: 1463–1469
Lubin R, Zalcman G, Bouchet L, Tredaniel J, Legros Y, Cazals D, Hirszh A and Soussi T (1995b Serum p53 antibodies as early markers of lung cancer. Nature Med 1, 7701–702
Marchetti A, Buttitta F, Merlo G, Diella F, Pellegrini S, Pepe S, Macchiarini P, Chella A, Angeletti CA, Callahan R, Bistocchi M and Squartini F (1993 P53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. Cancer Res 53: 2846–2851
McLaren R, Kuzu I, Dunnill M, Harris A, Lane D and Gatter KC (1992 The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer 66: 735–738
Mitsudomi T, Suzuki S, Yatabe Y, Nishio M, Kuwabara M, Gotoh K, Hatooka S, Shinoda M, Suyama M, Ogawa M, Takahashi T and Ariyoshi Y (1998 Clinical implications of p53 autoantibodies in the sera of patients with non-small-cell lung cancer. J Natl Cancer Inst 90: 1563–1568
Peyrat JP, Bonneterre J, Lubin R, Vanlemmens L, Fournier J and Soussi T (1995 Prognostic significance of circulating p53 antibodies in patients undergoing surgery for locoregional breast cancer. Lancet 345: 621–622
Quinlan DC, Davidson AG, Summers CL, Warden HE and Doshi HM (1992 Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res 52: 4828–4831
Rosenfeld MR, Malats N, Schramm L, Graus F, Cardenal F, Vinolas N, Rosell R, Tora M, Real FX, Posner JB and Dalmau J (1997 Serum p53 antibodies and prognosis of patients with small-cell lung carcinoma. J Natl Cancer Inst 89: 381–385
Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ, Hong WK, Komaki R, Lee JJ, Nesbitt JC, Pisters KM, Putnam JB, Schea R, Shin DM, Walsh GL, Dolormente MM, Han CI, Martin FD, Yen N, Xu K, Stephens LC, McDonnell TJ, Mukhopadhyay T and Cai D (1996 Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med 2, 9985–991
Rusch V, Klimstra D, Venkatraman E, Oliver J, Martini N, Gralla R, Kris M and Dmitrovsky E (1995 Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Can Res 55: 5038–5042
Schlichtholz B, Legros Y, Gillet D, Gaillard C, Marty M, Lane D, Calvo F and Soussi T (1992 The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res 52: 6380–6384
Segawa Y, Kageyama M, Suzuki S, Jinno K, Takigawa N, Fujimoto N, Hotta K and Eguchi K (1998 Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study. Br J Cancer 78: 667–672
Soussi T (1996 The humoral response to the tumor-suppressor gene-product p53 in human cancer: implications for diagnosis and therapy. Immunol Today 17: 354–356
Stahal RA, Ginsberg R and Havermann K (1989 Staging and prognostic factors in small cell lung carcinoma of the lung. Consensus report. Lung Cancer 5: 119–126
Waldman T, Lengauer C and Kinzler K (1996 Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. Nature 381: 713–716
Wallace-Brodeur RR and Lowe SW (1999 Clinical implications of p53 mutations. Cell Mol Life Sci 55: 64–75
Wild CP, Ridanpaa M, Anttila S, Lubin R, Soussi T, Husgafvel-Pursiainen K and Vainio H (1995 P53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue. Int J Cancer 64: 176–181
Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF and Carbone DP (1992 Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 52: 4168–4174
Zalcman G, Schlichtolz B, Tredaniel J, Urban T, Lubin R, Dubois I, Milleron B, Hirsch A and Soussi T (1998 Monitoring of p53 auto-antibodies in lung cancer during therapy: relationship to response to treatment. Clin Cancer Res 4: 1359–1366
Zalcman G, Tredaniel J, Schlichtholz B, Urban T, Milleron B, Lubin R, Meignin V, Coudrec L-J, Hirsch A and Soussi T (2000 Prognostic significance of serum p53 antibody in patients with limited stage small cell lung cancer. Int J Cancer 89, 181–86
Zang EA and Wynder EL (1996 Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst 88(3–4): 183–192
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Murray, P., Soussi, T., O’Brien, M. et al. Serum p53 antibodies: predictors of survival in small-cell lung cancer?. Br J Cancer 83, 1418–1424 (2000). https://doi.org/10.1054/bjoc.2000.1475
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DOI: https://doi.org/10.1054/bjoc.2000.1475
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