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.
Similar content being viewed by others
References
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.
Tsiouris A, Walesby RK. Malignant pleural mesothelioma: current concept in treatment. Nat Clin Practice Oncol. 2007;4:344–52.
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.
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.
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.
Lee AY, Raz DJ, He B, Jablons DM. Update on the molecular biology of malignant pleural mesothelioma. Cancer. 2007;109:1454–61.
Sculier JP, Berghmans T, Meert AP. Update in lung cancer and mesothelioma. Am J Respir Crit Care Med. 2010;181:773–81.
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.
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.
Ray M, Kindler HL. Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest. 2009;136:888–96.
Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 1972;175:409–16.
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.
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.
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.
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.
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.
Mancuso P, Rabascio C, Bertolini. Strategies to investigate circulating endothelial cells in cancer. Pathophysiol Haemost Thromb. 2004;33:503–6.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Alix-Panabières, C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res. 2008;14:5013–21.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-012-2506-0