Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Nov 22;83(11):1418–1424. doi: 10.1054/bjoc.2000.1475

Serum p53 antibodies: predictors of survival in small-cell lung cancer?

P V Murray 1, T Soussi 2, M E R O'Brien 1, I E Smith 1, S Brossault 2, A Norton 1, S Ashley 1, M Tavassoli 3
PMCID: PMC2363416  PMID: 11076647

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

Keywords: p53-antibodies, SCLC, tumour markers, chemotherapy

Full Text

The Full Text of this article is available as a PDF (551.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angelopoulou K., Diamandis E. P., Sutherland D. J., Kellen J. A., Bunting P. S. Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers. Int J Cancer. 1994 Aug 15;58(4):480–487. doi: 10.1002/ijc.2910580404. [DOI] [PubMed] [Google Scholar]
  2. Bergqvist M., Brattström D., Larsson A., Holmertz J., Hesselius P., Rosenberg L., Wagenius G., Brodin O. P53 auto-antibodies in non-small cell lung cancer patients can predict increased life expectancy after radiotherapy. Anticancer Res. 1998 May-Jun;18(3B):1999–2002. [PubMed] [Google Scholar]
  3. Bourhis J., Lubin R., Roche B., Koscielny S., Bosq J., Dubois I., Talbot M., Marandas P., Schwaab G., Wibault P. Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst. 1996 Sep 4;88(17):1228–1233. doi: 10.1093/jnci/88.17.1228. [DOI] [PubMed] [Google Scholar]
  4. Cote R. J., Esrig D., Groshen S., Jones P. A., Skinner D. G. p53 and treatment of bladder cancer. Nature. 1997 Jan 9;385(6612):123–125. doi: 10.1038/385123b0. [DOI] [PubMed] [Google Scholar]
  5. D'Amico D., Carbone D., Mitsudomi T., Nau M., Fedorko J., Russell E., Johnson B., Buchhagen D., Bodner S., Phelps R. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene. 1992 Feb;7(2):339–346. [PubMed] [Google Scholar]
  6. Davidoff A. M., Iglehart J. D., Marks J. R. Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3439–3442. doi: 10.1073/pnas.89.8.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Einhorn L. H., Crawford J., Birch R., Omura G., Johnson D. H., Greco F. A. Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer. J Clin Oncol. 1988 Mar;6(3):451–456. doi: 10.1200/JCO.1988.6.3.451. [DOI] [PubMed] [Google Scholar]
  8. Fritsche M., Haessler C., Brandner G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene. 1993 Feb;8(2):307–318. [PubMed] [Google Scholar]
  9. Fukuoka M., Furuse K., Saijo N., Nishiwaki Y., Ikegami H., Tamura T., Shimoyama M., Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855–861. doi: 10.1093/jnci/83.12.855. [DOI] [PubMed] [Google Scholar]
  10. Girling D. J. 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. 1996 Aug 31;348(9027):563–566. doi: 10.1016/s0140-6736(96)02005-3. [DOI] [PubMed] [Google Scholar]
  11. Harpole D. H., Jr, Herndon J. E., 2nd, Wolfe W. G., Iglehart J. D., Marks J. R. A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res. 1995 Jan 1;55(1):51–56. [PubMed] [Google Scholar]
  12. Houbiers J. G., van der Burg S. H., van de Watering L. M., Tollenaar R. A., Brand A., van de Velde C. J., Melief C. J. Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer. 1995 Sep;72(3):637–641. doi: 10.1038/bjc.1995.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Iizasa T., Fujisawa T., Saitoh Y., Hiroshima K., Ohwada H. Serum anti-p53 autoantibodies in primary resected non-small-cell lung carcinoma. Cancer Immunol Immunother. 1998 Aug;46(6):345–349. doi: 10.1007/s002620050496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirsch D. G., Kastan M. B. Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol. 1998 Sep;16(9):3158–3168. doi: 10.1200/JCO.1998.16.9.3158. [DOI] [PubMed] [Google Scholar]
  15. Komiya T., Hirashima T., Takada M., Masuda N., Yasumitsu T., Nakagawa K., Hosono Y., Kikui M., Tsuji S., Fukuoka M. Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung. Anticancer Res. 1997 Sep-Oct;17(5B):3721–3724. [PubMed] [Google Scholar]
  16. Kressner U., Glimelius B., Bergström R., Påhlman L., Larsson A., Lindmark G. Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer. Br J Cancer. 1998 Jun;77(11):1848–1851. doi: 10.1038/bjc.1998.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Laudanski J., Burzykowski T., Niklinska W., Chyczewski K., Furman M., Niklinski J. Prognostic value of serum p53 antibodies in patients with resected non-small cell lung cancer. Lung Cancer. 1998 Dec;22(3):191–200. doi: 10.1016/s0169-5002(98)00088-9. [DOI] [PubMed] [Google Scholar]
  18. Lee J. S., Yoon A., Kalapurakal S. K., Ro J. Y., Lee J. J., Tu N., Hittelman W. N., Hong W. K. Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor. J Clin Oncol. 1995 Aug;13(8):1893–1903. doi: 10.1200/JCO.1995.13.8.1893. [DOI] [PubMed] [Google Scholar]
  19. Lenner P., Wiklund F., Emdin S. O., Arnerlöv C., Eklund C., Hallmans G., Zentgraf H., Dillner J. Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study. Br J Cancer. 1999 Feb;79(5-6):927–932. doi: 10.1038/sj.bjc.6690148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Levine A. J., Perry M. E., Chang A., Silver A., Dittmer D., Wu M., Welsh D. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994 Mar;69(3):409–416. doi: 10.1038/bjc.1994.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lubin R., Schlichtholz B., Bengoufa D., Zalcman G., Trédaniel J., Hirsch A., Caron de Fromentel C., Preudhomme C., Fenaux P., Fournier G. 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. 1993 Dec 15;53(24):5872–5876. [PubMed] [Google Scholar]
  22. Lubin R., Schlichtholz B., Teillaud J. L., Garay E., Bussel A., Wild C. P. p53 antibodies in patients with various types of cancer: assay, identification, and characterization. Clin Cancer Res. 1995 Dec;1(12):1463–1469. [PubMed] [Google Scholar]
  23. 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 Jul;1(7):701–702. doi: 10.1038/nm0795-701. [DOI] [PubMed] [Google Scholar]
  24. Marchetti A., Buttitta F., Merlo G., Diella F., Pellegrini S., Pepe S., Macchiarini P., Chella A., Angeletti C. A., Callahan R. p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. Cancer Res. 1993 Jun 15;53(12):2846–2851. [PubMed] [Google Scholar]
  25. McLaren R., Kuzu I., Dunnill M., Harris A., Lane D., Gatter K. C. The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer. 1992 Oct;66(4):735–738. doi: 10.1038/bjc.1992.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mitsudomi T., Suzuki S., Yatabe Y., Nishio M., Kuwabara M., Gotoh K., Hatooka S., Shinoda M., Suyama M., Ogawa M. Clinical implications of p53 autoantibodies in the sera of patients with non-small-cell lung cancer. J Natl Cancer Inst. 1998 Oct 21;90(20):1563–1568. doi: 10.1093/jnci/90.20.1563. [DOI] [PubMed] [Google Scholar]
  27. Peyrat J. P., Bonneterre J., Lubin R., Vanlemmens L., Fournier J., Soussi T. Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer. Lancet. 1995 Mar 11;345(8950):621–622. doi: 10.1016/s0140-6736(95)90523-5. [DOI] [PubMed] [Google Scholar]
  28. Quinlan D. C., Davidson A. G., Summers C. L., Warden H. E., Doshi H. M. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res. 1992 Sep 1;52(17):4828–4831. [PubMed] [Google Scholar]
  29. Rosenfeld M. R., Malats N., Schramm L., Graus F., Cardenal F., Viñolas N., Rosell R., Torà M., Real F. X., Posner J. B. Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer. J Natl Cancer Inst. 1997 Mar 5;89(5):381–385. doi: 10.1093/jnci/89.5.381. [DOI] [PubMed] [Google Scholar]
  30. Roth J. A., Nguyen D., Lawrence D. D., Kemp B. L., Carrasco C. H., Ferson D. Z., Hong W. K., Komaki R., Lee J. J., Nesbitt J. C. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med. 1996 Sep;2(9):985–991. doi: 10.1038/nm0996-985. [DOI] [PubMed] [Google Scholar]
  31. Rusch V., Klimstra D., Venkatraman E., Oliver J., Martini N., Gralla R., Kris M., Dmitrovsky E. Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Cancer Res. 1995 Nov 1;55(21):5038–5042. [PubMed] [Google Scholar]
  32. Schlichtholz B., Legros Y., Gillet D., Gaillard C., Marty M., Lane D., Calvo F., Soussi T. The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res. 1992 Nov 15;52(22):6380–6384. [PubMed] [Google Scholar]
  33. Segawa Y., Kageyama M., Suzuki S., Jinno K., Takigawa N., Fujimoto N., Hotta K., Eguchi K. Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study. Br J Cancer. 1998 Sep;78(5):667–672. doi: 10.1038/bjc.1998.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Soussi T. The humoral response to the tumor-suppressor gene-product p53 in human cancer: implications for diagnosis and therapy. Immunol Today. 1996 Aug;17(8):354–356. doi: 10.1016/0167-5699(96)30019-4. [DOI] [PubMed] [Google Scholar]
  35. Waldman T., Lengauer C., Kinzler K. W., Vogelstein B. Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. Nature. 1996 Jun 20;381(6584):713–716. doi: 10.1038/381713a0. [DOI] [PubMed] [Google Scholar]
  36. Wallace-Brodeur R. R., Lowe S. W. Clinical implications of p53 mutations. Cell Mol Life Sci. 1999 Jan;55(1):64–75. doi: 10.1007/s000180050270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wild C. P., Ridanpä M., Anttila S., Lubin R., Soussi T., Husgafvel-Pursiainen K., Vainio H. p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue. Int J Cancer. 1995 Jun 22;64(3):176–181. doi: 10.1002/ijc.2910640306. [DOI] [PubMed] [Google Scholar]
  38. Winter S. F., Minna J. D., Johnson B. E., Takahashi T., Gazdar A. F., Carbone D. P. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res. 1992 Aug 1;52(15):4168–4174. [PubMed] [Google Scholar]
  39. Zalcman G., Schlichtholz B., Trédaniel J., Urban T., Lubin R., Dubois I., Milleron B., Hirsch A., Soussi T. Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. Clin Cancer Res. 1998 Jun;4(6):1359–1366. [PubMed] [Google Scholar]
  40. Zalcman G., Trédaniel J., Schlichtholz B., Urban T., Milleron B., Lubin R., Meignin V., Couderc L. J., Hirsch A., Soussi T. Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer. Int J Cancer. 2000 Jan 20;89(1):81–86. doi: 10.1002/(sici)1097-0215(20000120)89:1<81::aid-ijc13>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  41. Zang E. A., Wynder E. L. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst. 1996 Feb 21;88(3-4):183–192. doi: 10.1093/jnci/88.3-4.183. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES