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British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Apr;73(7):914–919. doi: 10.1038/bjc.1996.163

P53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer.

A Costa 1, R Silvestrini 1, C Mochen 1, C Lequaglie 1, P Boracchi 1, A Faranda 1, G Vessecchia 1, G Ravasi 1
PMCID: PMC2074267  PMID: 8611406

Abstract

The identification of biomarkers to complement pathological stage for a more accurate prognosis and help clinicians decide on treatment is still an open problem for patients with lung cancer. Expression of P53 protein was detected by an immunohistochemical approach using the monoclonal antibody PAb1801 on paraffin-embedded sections of tumours obtained surgically from 102 stage II - IIIa patients with non-small-cell lung cancer (52 squamous cell carcinomas, 50 adenocarcinomas). [3H]Thymidine labelling index, an indicator of the S-phase cell fraction, was evaluated on histological sections of [3H]thymidine-labelled tumour samples. DNA ploidy was defined by flow cytometric analysis on frozen tumour tissue. The biomarkers, histology and pathological stage were analysed in relation to relapse-free survival in univariate and multivariate analyses. Stage and interaction between [3H]thymidine labelling index and histology provided significant prognostic information for the overall series. [3H]thymidine labelling index was an independent prognostic indicator of 3 year relapse-free survival in patients with adenocarcinoma. The results indicate the importance of cell proliferation to complement prognostic information provided by pathological stage in patients with stage II-IIIa adenocarcinomas.

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Selected References

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  1. Alama A., Costantini M., Repetto L., Conte P. F., Serrano J., Nicolin A., Barbieri F., Ardizzoni A., Bruzzi P. Thymidine labelling index as prognostic factor in resected non-small cell lung cancer. Eur J Cancer. 1990;26(5):622–625. doi: 10.1016/0277-5379(90)90093-9. [DOI] [PubMed] [Google Scholar]
  2. Amadori D., Volpi A., Callea A., Amaducci L., Morgagni S., Magni E., Nanni O. Clinical relevance of cell kinetics in breast cancer. Ann N Y Acad Sci. 1993 Nov 30;698:186–192. doi: 10.1111/j.1749-6632.1993.tb17208.x. [DOI] [PubMed] [Google Scholar]
  3. Cibas E. S., Melamed M. R., Zaman M. B., Kimmel M. The effect of tumor size and tumor cell DNA content on the survival of patients with stage I adenocarcinoma of the lung. Cancer. 1989 Apr 15;63(8):1552–1556. doi: 10.1002/1097-0142(19890415)63:8<1552::aid-cncr2820630817>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  4. Costa A., Faranda A., Scalmati A., Quagliuolo V., Colella G., Ponz de Leon M., Silvestrini R. Autoradiographic and flow-cytometric assessment of cell proliferation in primary colorectal cancer: relationship to DNA ploidy and clinico-pathological features. Int J Cancer. 1992 Mar 12;50(5):719–723. doi: 10.1002/ijc.2910500509. [DOI] [PubMed] [Google Scholar]
  5. Costa A., Marasca R., Valentinis B., Savarino M., Faranda A., Silvestrini R., Torelli G. p53 gene point mutations in relation to p53 nuclear protein accumulation in colorectal cancers. J Pathol. 1995 May;176(1):45–53. doi: 10.1002/path.1711760108. [DOI] [PubMed] [Google Scholar]
  6. Ebina M., Steinberg S. M., Mulshine J. L., Linnoila R. I. Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. Cancer Res. 1994 May 1;54(9):2496–2503. [PubMed] [Google Scholar]
  7. Filderman A. E., Silvestri G. A., Gatsonis C., Luthringer D. J., Honig J., Flynn S. D. Prognostic significance of tumor proliferative fraction and DNA content in stage I non-small cell lung cancer. Am Rev Respir Dis. 1992 Sep;146(3):707–710. doi: 10.1164/ajrccm/146.3.707. [DOI] [PubMed] [Google Scholar]
  8. Isobe H., Miyamoto H., Shimizu T., Haneda H., Hashimoto M., Inoue K., Mizuno S., Kawakami Y. Prognostic and therapeutic significance of the flow cytometric nuclear DNA content in non-small cell lung cancer. Cancer. 1990 Mar 15;65(6):1391–1395. doi: 10.1002/1097-0142(19900315)65:6<1391::aid-cncr2820650624>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  9. Kerr K. M., Robertson A. M., Lamb D. In vitro thymidine labelling of human pulmonary neoplasms. Br J Cancer. 1983 Feb;47(2):245–252. doi: 10.1038/bjc.1983.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Le Chevalier T., Arriagada R., Quoix E., Ruffie P., Martin M., Tarayre M., Lacombe-Terrier M. J., Douillard J. Y., Laplanche A. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst. 1991 Mar 20;83(6):417–423. doi: 10.1093/jnci/83.6.417. [DOI] [PubMed] [Google Scholar]
  11. Marino P., Pampallona S., Preatoni A., Cantoni A., Invernizzi F. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994 Sep;106(3):861–865. doi: 10.1378/chest.106.3.861. [DOI] [PubMed] [Google Scholar]
  12. Martini N., Flehinger B. J. The role of surgery in N2 lung cancer. Surg Clin North Am. 1987 Oct;67(5):1037–1049. doi: 10.1016/s0039-6109(16)44341-0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Miyamoto H., Harada M., Isobe H., Akita H. D., Haneda H., Yamaguchi E., Kuzumaki N., Kawakami Y. Prognostic value of nuclear DNA content and expression of the ras oncogene product in lung cancer. Cancer Res. 1991 Dec 1;51(23 Pt 1):6346–6350. [PubMed] [Google Scholar]
  15. Mountain C. F. A new international staging system for lung cancer. Chest. 1986 Apr;89(4 Suppl):225S–233S. doi: 10.1378/chest.89.4_supplement.225s. [DOI] [PubMed] [Google Scholar]
  16. Mørkve O., Halvorsen O. J., Skjaerven R., Stangeland L., Gulsvik A., Laerum O. D. Prognostic significance of p53 protein expression and DNA ploidy in surgically treated non-small cell lung carcinomas. Anticancer Res. 1993 May-Jun;13(3):571–578. [PubMed] [Google Scholar]
  17. Naruke T., Goya T., Tsuchiya R., Suemasu K. The importance of surgery to non-small cell carcinoma of lung with mediastinal lymph node metastasis. Ann Thorac Surg. 1988 Dec;46(6):603–610. doi: 10.1016/s0003-4975(10)64717-0. [DOI] [PubMed] [Google Scholar]
  18. Paradiso A., Mangia A., Barletta A., Catino A. M., Giannuzzi A., Schittulli F., Radogna N., Longo S., Palmieri D., Marzullo F. Randomised clinical trial of adjuvant chemotherapy in patients with node-negative, fast-proliferating breast cancer. Drugs. 1993;45 (Suppl 2):68–74. doi: 10.2165/00003495-199300452-00011. [DOI] [PubMed] [Google Scholar]
  19. Passlick B., Izbicki J. R., Riethmüller G., Pantel K. p53 in non-small-cell lung cancer. J Natl Cancer Inst. 1994 May 18;86(10):801–803. doi: 10.1093/jnci/86.10.801. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Scagliotti G. V., Micela M., Gubetta L., Leonardo E., Cappia S., Borasio P., Pozzi E. Prognostic significance of Ki67 labelling in resected non small cell lung cancer. Eur J Cancer. 1993;29A(3):363–365. doi: 10.1016/0959-8049(93)90387-u. [DOI] [PubMed] [Google Scholar]
  22. Silvestrini R., Benini E., Daidone M. G., Veneroni S., Boracchi P., Cappelletti V., Di Fronzo G., Veronesi U. p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst. 1993 Jun 16;85(12):965–970. doi: 10.1093/jnci/85.12.965. [DOI] [PubMed] [Google Scholar]
  23. Tungekar M. F., Gatter K. C., Dunnill M. S., Mason D. Y. Ki-67 immunostaining and survival in operable lung cancer. Histopathology. 1991 Dec;19(6):545–550. doi: 10.1111/j.1365-2559.1991.tb01503.x. [DOI] [PubMed] [Google Scholar]
  24. Volm M., Drings P., Mattern J., Sonka J., Vogt-Moykopf I., Wayss K. Prognostic significance of DNA patterns and resistance-predictive tests in non-small cell lung carcinoma. Cancer. 1985 Sep 15;56(6):1396–1403. doi: 10.1002/1097-0142(19850915)56:6<1396::aid-cncr2820560630>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]

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