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Maspin, VEGF and p53 Expression in Small Biopsies of Primary Advanced Lung Cancer and Relationship with Clinicopathologic Parameters

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Pathology & Oncology Research

Abstract

Maspin, one of the serine protease inhibitors, has been shown to inhibit tumor progression and metastasis. We aimed to investigate maspin, p53 and VEGF expression in patients with squamous cell carcinoma (SCC), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). The study included 28 SCC, 18AC, 17 SCLC biopsy samples. We used the streptavidin biotin immunoperoxidase method to test for maspin, p53 and VEGF antibodies. Medical records of these patients were reviewed from archival files. Cytoplasmic maspin expression was detected in 89.3%, 77.8%, 52.9% of SCC, AC and SCLC, respectively. The rate was significantly higher in non-small cell lung cancer (NSCLC) and SCC than SCLC (p = 0.013, p = 0.021, respectively). The mean percentages of maspin expression were significantly higher in NSCLC, SCC and AC than in SCLC (p = 0.0001, p = 0.0001, p = 0.038, respectively). In ACs, maspin and p53 expressions were correlated, although this was not statistically significant (p = 0.053, r = 0.464), and maspin positive cases had a significantly higher T status compared to negative cases (p = 0.036). In SCC, the stage of disease was positively correlated with p53 (p = 0.007, r = 0.536) and negatively correlated with VEGF expression (p = 0.013, r = −0.498). Multivariate analysis demonstrated that stage of disease was a significant independent prognostic parameter in NSCLC (95% confidence interval: 1.067–3.969; p = 0.031). Although maspin expression is higher in SCC and AC, and is related with higher T status in AC, our data did not indicate its prognostic significance. Larger scale studies are needed to reveal the exact role of maspin in lung cancer pathogenesis.

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References

  1. Zou Z, Anisowicz A, Hendrix MJ et al (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263:526–529

    Article  CAS  PubMed  Google Scholar 

  2. Chen EI, Yates JR (2006) Maspin and tumor metastasis. IUBMB Life 58:25–29

    Article  CAS  PubMed  Google Scholar 

  3. Bailey CM, Khalkhali-Ellis Z, Seftor EA et al (2006) Biological functions of Maspin. J Cell Physiol 209:617–624

    Article  CAS  PubMed  Google Scholar 

  4. Lockett J, Yin S, Li X et al (2006) Tumor suppressive maspin and epithelial homeostasis. J Cell Biochem 97:651–660

    Article  CAS  PubMed  Google Scholar 

  5. Zhang M, Volpert O, Shi YH et al (2000) Maspin is an angiogenesis inhibitor. Nat Med 6:196–199

    Article  PubMed  Google Scholar 

  6. Nakagawa M, Katakura H, Adachi M et al (2006) Maspin expression and its clinical significance in non-small cell lung cancer. Ann Surg Oncol 13:1517–1523

    Article  PubMed  Google Scholar 

  7. Woenckhaus M, Bubendorf L, Dalquen P et al (2007) Nuclear and cytoplasmic maspin expression in primary non-small cell lung cancer. J Clin Pathol 60:483–486

    Article  CAS  PubMed  Google Scholar 

  8. Takanami I, Abiko T, Koizumi S (2008) Expression of maspin in non-small-cell lung cancer: correlation with clinical features. Clin Lung Cancer 9:361–366

    Article  PubMed  Google Scholar 

  9. Katakura H, Takenaka K, Nakagawa M et al (2006) Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer (NSCLC). Maspin in NSCLC. Lung Cancer 51:323–328

    Article  PubMed  Google Scholar 

  10. Hirai K, Koizumi K, Haraguchi S et al (2005) Prognostic significance of the tumor suppressor gene maspin in non-small cell lung cancer. Ann Thorac Surg 79:248–253

    Article  PubMed  Google Scholar 

  11. Zheng HC, Saito H, Masuda S et al (2008) Cytoplasmic and nuclear maspin expression in lung carcinomas: an immunohistochemical study using tissue microarrays. App Immunohistochem Mol Morphol 16:459–465

    Article  CAS  Google Scholar 

  12. Nakashima M, Ohike N, Nagasaki K et al (2004) Prognostic significance of the maspin tumor suppressor gene in pulmonary adenocarcinoma. J Cancer Res Clin Oncol 130:475–479

    Article  CAS  PubMed  Google Scholar 

  13. Lonardo F, Li X, Siddiq F et al (2006) Maspin nuclear localization is linked to favorable morphological features in pulmonary adenocarcinoma. Lung Cancer 51:31–39

    Article  PubMed  Google Scholar 

  14. Frey A, Soubani AO, Adam AK et al (2009) Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival. Histopathology 54:590–597

    Article  PubMed  Google Scholar 

  15. Yilmaz A, Ernam D, Unsal E et al (2007) Vascular endothelial growth factor immunostaining correlates with postoperative relapse and survival in non-small cell lung cancer. Arch Med Res 38:764–768

    Article  CAS  PubMed  Google Scholar 

  16. Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143–158

    Article  PubMed  Google Scholar 

  17. Boldrini L, Gisfredi S, Ursino S et al (2005) Interleukin-8 in non-small cell lung carcinoma: relation with angiogenic pattern and p53 alterations. Lung Cancer 50:309–317

    Article  PubMed  Google Scholar 

  18. Zhu CQ, Shih W, Ling CH et al (2006) Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol 59:790–800

    Article  CAS  PubMed  Google Scholar 

  19. Hollstein M, Sidransky D, Volgestein B et al (1991) p53 mutation in human cancers. Science 253:49–53

    Article  CAS  PubMed  Google Scholar 

  20. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press, Lyon

    Google Scholar 

  21. Ludovini V, Gregorc V, Pistola L et al (2004) Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer. Lung Cancer 46:77–85

    Article  PubMed  Google Scholar 

  22. Freemantle SJ, Dmitrovsky E (2002) Clinical link between p53 and angiogenesis in lung cancer. J Clin Oncol 20:883–884

    CAS  PubMed  Google Scholar 

  23. Yuan A, Yu CJ, Luh KT et al (2002) Aberrant p53 expression correlates with expression of vascular endothelial growth factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung cancer. J Clin Oncol 20:900–910

    Article  CAS  PubMed  Google Scholar 

  24. Mukhopadhyay D, Tsiokas L, Sukhatme VP (1995) Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res 57:6161–6165

    Google Scholar 

  25. Zou Z, Gao C, Nagaich AK et al (2000) p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem 275:6051–6054

    Article  CAS  PubMed  Google Scholar 

  26. Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655

    Article  CAS  PubMed  Google Scholar 

  27. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111:1710–1717

    Article  CAS  PubMed  Google Scholar 

  28. Stahel RA, Ginsberg R, Havemann K et al (1989) Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer 5:119–126

    Article  Google Scholar 

  29. Smith SL, Watson SG, Ratschiller D et al (2003) Maspin- the most commonly expressed gene of the 18q21.3 serpin cluster in lung cancer- is strongly expressed in preneoplastic bronchial lesions. Oncogene 22:8677–8687

    Article  CAS  PubMed  Google Scholar 

  30. Steels E, Paesmans M, Berghamans T et al (2001) Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 18:705–719

    Article  CAS  PubMed  Google Scholar 

  31. Laudanski J, Niklinska W, Burzykowski T et al (2001) Prognostic significance of p53 and bcl-2 abnormalities in operable nonsmall cell lung cancer. Eur Respir J 17:660–666

    Article  CAS  PubMed  Google Scholar 

  32. Tsao MS, Aviel-Ronen S, Ding K et al (2007) Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. J Clin Oncol 25:5240–5247

    Article  PubMed  Google Scholar 

  33. O’Byrne KJ, Koukourakis MI, Giatromanolaki A et al (2000) Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 82:1427–1432

    PubMed  Google Scholar 

  34. Fontanini G, Boldrini L, Vignati S et al (1998) Bcl-2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma. Eur J Cancer 34:718–723

    Article  CAS  PubMed  Google Scholar 

  35. Yoo J, Yung JH, Lee MA et al (2007) Immunohistochemical analysis of non-small cell lung cancer: correlation with clinical parameters and prognosis. J Korean Med Sci 22:318–325

    Article  PubMed  Google Scholar 

  36. Ito H, Oshita F, Kameda Y et al (2002) Expression of vascular endothelial growth factor and basic fibroblast growth factor in small adenocarcinomas. Oncol Rep 9:119–123

    CAS  PubMed  Google Scholar 

  37. Seto T, Higashiyama M, Funai H et al (2006) Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small- cell lung cancer. Lung Cancer 53:91–96

    Article  PubMed  Google Scholar 

  38. Liao M, Wang H, Lin Z et al (2001) Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer. Lung Cancer 33:125–132

    Article  CAS  PubMed  Google Scholar 

  39. Nakashima T, Huang CL, Liu D et al (2004) Expression of vascular endothelial growth factor-A and vascular endothelial growth factor-C as prognostic factors for non small cell lung cancer. Med Sci Monit 10:BR157–BR165

    CAS  PubMed  Google Scholar 

  40. Niklinska W, Burzykowski T, Chyczewski L, Niklinski J (2001) Expression of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC): association with p53 gene mutation and prognosis. Lung Cancer 34:S59–S64

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Turkish Association for Cancer Research and Control, Terry Fox Foundation. The authors also thank Mr. Vasfi Baran for his technical assistance.

Conflict of Interest Statement

All authors declare that there are no conflicts of interest.

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Correspondence to Ahmet Bircan.

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Bircan, A., Bircan, S., Kapucuoglu, N. et al. Maspin, VEGF and p53 Expression in Small Biopsies of Primary Advanced Lung Cancer and Relationship with Clinicopathologic Parameters. Pathol. Oncol. Res. 16, 553–561 (2010). https://doi.org/10.1007/s12253-010-9259-5

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  • DOI: https://doi.org/10.1007/s12253-010-9259-5

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