European Journal of Cancer
Volume 39, Issue 9 , Pages 1242-1250 , June 2003

Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers

  • F Grossi

      Affiliations

    • Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
    • ,
  • M Loprevite

      Affiliations

    • Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
    • ,
  • M Chiaramondia

      Affiliations

    • Department of Pathology, S. Martino Hospital, Genoa, Italy
    • ,
  • P Ceppa

      Affiliations

    • Department of Pathology, University of Genoa, Italy
    • ,
  • C Pera

      Affiliations

    • Immunogenetics Laboratory, Istituto Nazionale per la Ricerca sul Cancro c/o Advanced Biotecnology Center, Genoa, Italy
    • ,
  • G.B Ratto

      Affiliations

    • Department of Thoracic Surgery, University of Genoa, Italy
    • ,
  • J Serrano

      Affiliations

    • Department of Thoracic Surgery, S. Martino Hospital, Genoa, Italy
    • ,
  • G.B Ferrara

      Affiliations

    • Immunogenetics Laboratory, Istituto Nazionale per la Ricerca sul Cancro c/o Advanced Biotecnology Center, Genoa, Italy
    • ,
  • R Costa

      Affiliations

    • Department of Thoracic Surgery, University of Genoa, Italy
    • ,
  • L Boni

      Affiliations

    • Data Center, Advanced Biotechnology Center, Genoa, Italy
    • ,
  • A Ardizzoni

      Affiliations

    • Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39-010-560-0898; fax: +39-010-560-0850

Received 17 July 2002 ,Revised 31 January 2003 ,Accepted 4 March 2003.

References 

  1. Jemal A, Thomas A, Murray T, Thun M. Cancer Statistics, 2002. CA Cancer J. Clin. 2002;52:23–47
  2. Ginsberg RJ, Vokes EE, Raben A. Non-small cell lung cancer. In:  De Vita VT,  Hellman S,  Rosenberg SA editor. Cancer Principles and Practice of Oncology V. 5th edn.. Philadelphia: JB Lippincot Co; 2001;p. 925–978
  3. Gail MH, Eagan RT, Feld R, et al.  Prognostic factors in patients with resected stage I non-small cell lung cancer (a report from The Lung Cancer Study Group). Cancer. 1984;54:1802–1813
  4. Lipford EH, Eggleston JC, Lillemoe KD, Sears DL, Moore GW, Baker RR. Prognostic factors in surgically resected limited-stage, non-small cell carcinoma of the lung. Am. J. Surg. Pathol. 1984;8:357–365
  5. Marchetti A, Buttitta F, Merlo G, et al.  p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. Cancer Res. 1993;53:2846–2851
  6. Rodenhuis S, Slebos RJ, Boot AJ, et al.  Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res. 1988;48:5738–5741
  7. Sugio K, Ishida T, Yokoyama H, et al.  ras gene mutations as a prognostic marker in adenocarcinoma of the human lung without lymph node metastasis. Cancer Res. 1992;52:2903–2906
  8. Fontanini G, Lucchi M, Vignati S, et al.  Angiogenesis as a prognostic indicator of survival in non-small cell lung carcinoma (a prospective study). J. Natl. Cancer Inst. 1997;89:881–886
  9. Yano T, Tanikawa S, Fujie T, Masutani M, Horie T. Vascular endothelial growth factor expression and neovascularisation in non-small cell lung cancer. Eur. J. Cancer. 2000;26:601–609
  10. Fontanini G, Macchiarini P, Pepe S, et al.  The expression of Proliferating Cell Nuclear Antigen in paraffin sections of peripheral, node-negative non-small cell lung cancer. Cancer. 1992;70:1520–1527
  11. World Health Organization . The World Health Organization histological typing of lung cancer. Am. J. Clin. Pathol. 1982;77:123–136
  12. Colby TV, Koss MN, Travis WT. Tumors of the Lower Respiratory Tract. Washington, DC: Armed Forces Institute of Pathology (AFIP); 1995;
  13. Mountain CF. A new international staging system for lung cancer. Chest. 1986;89:225–323
  14. Kaplan EL, Meier P. Non parametric estimation from incomplete observations. J. Am. Stat. Assoc. 1958;53:457–481
  15. Miller RG. Survival Analysis. New York: John Wiley; 1981; 44–102
  16. Mitsudomi T, Hamajima N, Ogawa M, Takahashi T. Prognostic significance of p53 alterations in patients with non-small cell lung cancer (a meta-analysis). Clin. Cancer Res. 2000;6:4055–4063
  17. Harpole DH, Herdon JE, Wolfe WG. A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res. 1995;55:51–56
  18. Ishida H, Irie K, Itoh T, Furukawa T, Tokunaga O. The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction. Cancer. 1997;80:1034–1045
  19. Pastorino U, Andreola S, Tagliabue E, et al.  Immunocytochemical markers in stage I lung cancer (relevance to prognosis). J. Clin. Oncol. 1997;15:2858–2865
  20. Westra WH, Offerhaus JA, Goodman SN, Slebos RJ, Polak M, Baas IO. Overexpression of p53 tumor suppressor gene product in primary lung adenocarcinomas is associated with cigarette smoking. Am. J. Surg. Pathol. 1993;17:213–220
  21. Kashii T, Mizushima Y, Lima CEQ, et al.  Studies on clinico-pathological features of lung cancer patients with K-ras/p53 gene alterations (comparison between younger and older groups). Oncology. 1995;52:219–225
  22. Schiller JH, Adak S, Feins RH, et al.  Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592 (a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy). J. Clin. Oncol. 2001;19:448–457
  23. Top B, Mooi WJ, Klaver SG, et al.  Comparative analysis of p53 gene mutations and protein accumulation in human non-small cell lung cancer. Int. J. Cancer. 1995;64:83–91
  24. Passlick B, Izbicki JR, Riethmuller G, Pantel K. p53 in non-small cell lung cancer. J. Natl. Cancer Inst. 1994;86:801–802
  25. Oyama T, Osaki T, Nose N, et al.  Evaluations of p53 immunoreactivity, nucleolar organizer regions and proliferating cell nuclear antigen in non-small cell lung carcinoma. Anticancer Res. 2000;20:505–510
  26. Borner MM, Brousset P, Pfanner-Meyer B, et al.  Expression of apoptosis regulatory proteins of the bcl-2 family and p53 in primary resected non-small cell lung cancer. Br. J. Cancer. 1999;79:952–958
  27. Fontanini G, Vignati S, Bigini D, et al.  Bcl-2 protein (a prognostic factor inversely correlated to p53 in non-small cell lung cancer). Br. J. Cancer. 1995;71:1003–1007
  28. Silvestrini R, Veneroni S, Daidone MG, et al.  The bcl-2 protein (a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients). J. Natl. Cancer Inst. 1994;86:499–504
  29. Slebos RJ, Kibbelaar RE, Dalesio O, et al.  K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N. Engl. J. Med. 1990;323:561–565
  30. Mitsudomi T, Steinberg SM, Oie HK, et al.  ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent. Cancer Res. 1991;51:4999–5002
  31. Graziano SL. Non-small cell lung cancer (clinical value of new biological predictors). Lung Cancer. 1997;17(Suppl. 1):S37–S58
  32. Graziano SL, Gamble GP, Newman NB, et al.  Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small cell lung cancer. J. Clin. Oncol. 1999;17:668–675
  33. Miyake M, Adachi M, Huang CI, et al.  A novel molecular staging protocol for non-small cell lung cancer. Oncogene. 1999;18:2397–2404
  34. Fukuyama Y, Mitsudomi T, Sugio K, Ishida T, Akazawa K, Sugimachi K. K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small cell lung cancer. Br. J. Cancer. 1997;75:1125–1130
  35. Huncharek M, Muscat J, Geschwind JF. K-ras mutation as a prognostic marker in non-small cell lung cancer (a combined analysis of 881 cases). Carcinogenesis. 1999;20:1507–1510
  36. Rosell R, Monzo M, Pifarre A, et al.  Molecular staging of non-small cell lung cancer according to K-ras genotypes. Clin. Cancer Res. 1996;2:1083–1086
  37. Keohavong P, De Michele MMA, Melacrinos AC, Landreneau RJ, Weyant RJ, Siegfried JM. Detection of K-ras mutations in lung carcinomas (relationship to prognosis). Clin Cancer Res. 1996;2:411–418
  38. Kwiatkowski DJ, Harpole DH, Godleski J, et al.  Molecular pathologic substaging in 244 stage I non-small cell lung cancer (clinical implications). J. Clin. Oncol. 1998;17:2468–2477
  39. Jacobson DR, Fishman CL, Mills NE. Molecular genetic tumor markers in the early diagnosis and screening of non-small cell lung cancer. Annals Oncol. 1995;6(Suppl. 3):S3–S8
  40. Cho JY, Kim JH, Lee YH, et al.  Correlation between K-ras gene mutation and prognosis of patients with non-small cell lung carcinoma. Cancer. 1997;79:462–467
  41. Pezzella F, Turley H, Kuzu I, et al.  Bcl-2 protein in non-small cell lung carcinoma. New Engl. J. Med. 1993;329:690–694
  42. Aydanur HK, Safiye A, Ozgul S. Apoptosis bcl-2 and p53 expression and their relation to tumour stage in non-small cell lung carcinomas (NSCLC). Cancer Lett. 1997;116:185–189
  43. Ritter JH, Dresler CM, Wick MR. Expression of bcl-2 protein in stage T1N0M0 non-small cell lung carcinoma. Hum. Pathol. 1995;26:1227–1232
  44. Dosaka-Akita H, Katabami M, Hommura H, Fujioka Y, Katoh H, Kawakami Y. Bcl-2 expression in non-small cell lung cancers (higher frequency of expression in squamous cell carcinomas with earlier pT status). Oncology. 1999;56:259–264
  45. Törmänen U, Eerola A-K, Rainio P, et al.  Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res. 1995;55:5595–5602
  46. Dworakowska D, Gozdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A. Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer. Lung Cancer. 2002;35:35–41
  47. Volm M, Koomägi R. Relevance of proliferative and pro-apoptotic factors in non-small-cell lung cancer for patient survival. Br. J. Cancer. 2000;82:1747–1754
  48. Merkel DE, McGuire WL. Ploidy, proliferative activity and prognosis. Cancer. 1990;65:1194–1205
  49. Mattern J, Koomagi R, Volm M. Biological characterization of subgroups of squamous cell lung carcinomas. Clin. Cancer Res. 1999;5:1459–1463
  50. Ebina M, Steinberg ST, Mulshine JL, Linnoila RI. 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;54:2496–2503
  51. Vermeulen PB, Gasparini G, Fox SB, et al.  Quantification of angiogenesis in solid human tumors (an international consensus on the methodology and criteria of evaluation). Eur. J. Cancer. 1996;32:2474–2484
  52. Decaussin M, Sartelet H, Robert C, et al.  Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk-1/KDR) in non-small cell lung carcinomas (NSCLCs) (correlation with angiogenesis and survival). J. Pathol. 1999;188:369–377

PII: S0959-8049(03)00232-6

doi: 10.1016/S0959-8049(03)00232-6

European Journal of Cancer
Volume 39, Issue 9 , Pages 1242-1250 , June 2003

Article Tools

* Image Usage & Resolution