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Circulating Endothelial Cell (CEC) as a Diagnostic and Prognostic Marker in Malignant Pleural Mesothelioma (MPM)

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The purpose of this study was to investigate the diagnostic and prognostic value of circulating endothelial cell (CEC), a potential surrogate of tumor angiogenesis, in malignant pleural mesothelioma (MPM).

Methods

We prospectively evaluated CEC count in 4.0 mL of peripheral blood sampled from patients with a suspicion of MPM. An automated system was used to capture CECs with an anti-CD146 antibody.

Results

Of 109 eligible patients, 30 were finally diagnosed with non-malignant diseases, and 79 were with MPM. CEC count was significantly higher in MPM patients than in NM patients (mean CEC count, 120.3 and 39.9, respectively; P = 0.001), and a receiver operating characteristic (ROC) curve analysis showed that CEC provided a significant diagnostic performance in discrimination between MPM and nonmalignant diseases with an area under curve (AUC–ROC) of 0.700 (95 % confidence interval [95 % CI], 0.595–0.806; P = 0.001). Among MPM patients, CEC count was positively correlated with intratumoral microvessel density (MVD), a measurement of tumor angiogenesis (Spearman correlation coefficiency [r] = 0.444; P = 0.001). Higher CEC count (>50) was significantly associated with a poor prognosis (median overall survival, 11.4 months [95 % CI, 7.6–15.2] for higher CEC count patients versus 20.1 months [95 % CI, 16.0–24.2] for lower CEC count patients; P = 0.028). A multivariate analysis showed that higher CEC count was a significant and independent factor to predict a poor prognosis (hazard ratio [HR], 2.24, [95 % CI, 1.24–4.43]; P = 0.009).

Conclusions

CEC, as a surrogate of tumor angiogenesis, was a promising marker in diagnosis and prediction of prognosis in MPM.

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References

  1. Ismail-Khan R, Robinson LA, Williams CC, Garrett CR, Bepler G, Siomn G. Malignant pleural mesothelioma: a comprehensive review. Cancer Control. 2006;13:255–63.

    PubMed  Google Scholar 

  2. Tsiouris A, Walesby RK. Malignant pleural mesothelioma: current concept in treatment. Nat Clin Practice Oncol. 2007;4:344–52.

    Article  Google Scholar 

  3. Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, de Vuyst P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J. 2010;35:479–95.

    Article  PubMed  CAS  Google Scholar 

  4. Stahel RA, Weder W, Lievens Y, Felip E. Malignant pleural mesothelioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:v126–8.

    Article  PubMed  Google Scholar 

  5. van der Bij S, Schaake E, Koffijberg H, Burgers JA, de Mol BAJM, Moons KGM. Markers for the non-invasive diagnosis of mesothelioma: a systematic review. Br J Cancer. 2011;104:1325–33.

    Article  PubMed  Google Scholar 

  6. Lee AY, Raz DJ, He B, Jablons DM. Update on the molecular biology of malignant pleural mesothelioma. Cancer. 2007;109:1454–61.

    Article  PubMed  CAS  Google Scholar 

  7. Sculier JP, Berghmans T, Meert AP. Update in lung cancer and mesothelioma. Am J Respir Crit Care Med. 2010;181:773–81.

    Article  PubMed  CAS  Google Scholar 

  8. Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systemic review of extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Oncol. 2010;5:1692–703.

    Article  PubMed  Google Scholar 

  9. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–44.

    Article  PubMed  CAS  Google Scholar 

  10. Ray M, Kindler HL. Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest. 2009;136:888–96.

    Article  PubMed  Google Scholar 

  11. Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 1972;175:409–16.

    Article  PubMed  CAS  Google Scholar 

  12. Yano S, Li Q, Wang W, Yamada T, Takeuchi S, Nakataki E, et al. Antiangiogenic therapies for malignant pleural mesothelioma. Front Biosci. 2011;16:740–8.

    Article  PubMed  CAS  Google Scholar 

  13. Ohta Y, Shridhar Y, Bright RK, Kalemkerian GP, Du W, Carbone M, et al. VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. Br J Cancer. 1999;81:54–61.

    Article  PubMed  CAS  Google Scholar 

  14. Kumar-Singh S, Weyler J, Martin MJ, Vermeulen PB, E. van Marck. Angiogenic cytokines in mesothelioma: a study of VEGF, FGF-1 and -2, and TGF beta expression. J Pathol. 1999;189:72–8.

    Article  PubMed  CAS  Google Scholar 

  15. Tolnay E, Kuhnen C, Wiethege T, König JE, Voss B, Müller KM. Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. J Cancer Res Clin Oncol. 1998;124:291–6.

    Article  PubMed  CAS  Google Scholar 

  16. Monestiroli S, Mancuso P, Burlini A, Pruneri G, Dell’Agnola C, Gobbi A, et al. Kinetics and viability of circulating endothelial cells as surrogate of angiogenesis marker in an animal model of human lymphoma. Cancer Res. 2001;61:4341–4.

    PubMed  CAS  Google Scholar 

  17. Mancuso P, Rabascio C, Bertolini. Strategies to investigate circulating endothelial cells in cancer. Pathophysiol Haemost Thromb. 2004;33:503–6.

    Article  Google Scholar 

  18. Strijbos MH, Gratama JW, Kraan J, Lamers CH, den Bakker, Sleijfer S. Circulating endothelial cells in oncology: pitfalls and promises. Br J Cancer. 2008;98:1731–5.

    Article  PubMed  CAS  Google Scholar 

  19. Beerepoot LV, Mehra N, Vermaat JSP, Zonnenberg BA, Gebbink MFGB, Voest EE. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15:139–45.

    Article  PubMed  CAS  Google Scholar 

  20. Kawaishi M, Fujiwara Y, Fukui T, et al. Circulating endothelial cells in non-small cell lung cancer patients treated with carboplatin and paclitaxel. J Thorac Oncol. 2009; 4:208-13.

    Article  PubMed  Google Scholar 

  21. Rowand JL, Martin G, Doyle GV, Miller MC, Pierce MS, Connelly MC, et al. Endothelial cells in peripheral blood of healthy subjects and patients with metastatic carcinomas. Cytometry Part A. 2007;71A:105–13.

    Article  Google Scholar 

  22. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma from the international mesothelioma interest group. Lung Cancer. 1996;14:1–12.

    Article  PubMed  CAS  Google Scholar 

  23. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med. 2001;7:1194–201.

    Article  PubMed  CAS  Google Scholar 

  24. Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, et al. Contribution of bone-marrow-derived endothelial cells to human tumor vasculature. Nat Med. 2005;11:261–2.

    Article  PubMed  CAS  Google Scholar 

  25. Ronzoni M, Manzoni M, Mariucci S, Loupakis F, Brugnatelli S, Bencardino K, et al. Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients. Ann Oncol. 2010;21:2382–9.

    Article  PubMed  CAS  Google Scholar 

  26. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.

    Article  PubMed  Google Scholar 

  27. Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, et al. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009;15:6980–6.

    Article  PubMed  CAS  Google Scholar 

  28. Alix-Panabières, C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res. 2008;14:5013–21.

    Article  PubMed  Google Scholar 

  29. Curren D, Sahmound T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of cancer experience. J Clin Oncol. 1998;16:145–52.

    Google Scholar 

  30. Fennell DA, Parmer A, Shamash J, Evans MT, Sheaff MT, Sylvester R, et al. Statistical validation of the EORTC prognostic model for malignant pleural mesothelioma based on three consecutive phase II studies. J Clin Oncol. 2005;23:184–9.

    Article  PubMed  Google Scholar 

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Acknowledgment

This study was supported by The Special Coordination Funds for Promoting Science and Technology from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Grants-in-Aid for Scientific Research (KAKENHI B 24390335) from the Japan Society for the Promotion of Science (JSPS), and UOEH Grant for Advanced Research (H24-1) from University of Occupational and Educational Health.

Conflict of interest

None declared.

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Corresponding author

Correspondence to Fumihiro Tanaka MD, PhD.

Appendix

Appendix

See Figs. 5, 6 and Table 3

Fig. 5
figure 5

Flowchart of diagnosis of patients enrolled in the study

Fig. 6
figure 6

Immunohistochemical staining with an anti-CD34 antibody in malignant pleural mesothelioma (MPM) to evaluate intratumoral microvessel density (MVD)

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Yoneda, K., Tanaka, F., Kondo, N. et al. Circulating Endothelial Cell (CEC) as a Diagnostic and Prognostic Marker in Malignant Pleural Mesothelioma (MPM). Ann Surg Oncol 19, 4229–4237 (2012). https://doi.org/10.1245/s10434-012-2506-0

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  • DOI: https://doi.org/10.1245/s10434-012-2506-0

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