Skip to main content
Top
Published in: Annals of Surgical Oncology 13/2012

01-12-2012 | Thoracic Oncology

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

Authors: Kazue Yoneda, BA, Fumihiro Tanaka, MD, PhD, Nobuyuki Kondo, MD, PhD, Hayato Orui, MD, Masaki Hashimoto, MD, Teruhisa Takuwa, MD, Seiji Matsumoto, MD, PhD, Yoshitomo Okumura, MD, PhD, Noriaki Tsubota, MD, PhD, Ayuko Sato, PhD, Tohru Tsujimura, MD, PhD, Kozo Kuribayashi, MD, PhD, Kazuya Fukuoka, MD, PhD, Takashi Nakano, MD, PhD, Seiki Hasegawa, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2012

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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 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
2.
go back to reference Tsiouris A, Walesby RK. Malignant pleural mesothelioma: current concept in treatment. Nat Clin Practice Oncol. 2007;4:344–52.CrossRef Tsiouris A, Walesby RK. Malignant pleural mesothelioma: current concept in treatment. Nat Clin Practice Oncol. 2007;4:344–52.CrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference Lee AY, Raz DJ, He B, Jablons DM. Update on the molecular biology of malignant pleural mesothelioma. Cancer. 2007;109:1454–61.PubMedCrossRef Lee AY, Raz DJ, He B, Jablons DM. Update on the molecular biology of malignant pleural mesothelioma. Cancer. 2007;109:1454–61.PubMedCrossRef
7.
go back to reference Sculier JP, Berghmans T, Meert AP. Update in lung cancer and mesothelioma. Am J Respir Crit Care Med. 2010;181:773–81.PubMedCrossRef Sculier JP, Berghmans T, Meert AP. Update in lung cancer and mesothelioma. Am J Respir Crit Care Med. 2010;181:773–81.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference Ray M, Kindler HL. Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest. 2009;136:888–96.PubMedCrossRef Ray M, Kindler HL. Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest. 2009;136:888–96.PubMedCrossRef
11.
go back to reference Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 1972;175:409–16.PubMedCrossRef Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 1972;175:409–16.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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 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
17.
go back to reference Mancuso P, Rabascio C, Bertolini. Strategies to investigate circulating endothelial cells in cancer. Pathophysiol Haemost Thromb. 2004;33:503–6.CrossRef Mancuso P, Rabascio C, Bertolini. Strategies to investigate circulating endothelial cells in cancer. Pathophysiol Haemost Thromb. 2004;33:503–6.CrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference Alix-Panabières, C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res. 2008;14:5013–21.PubMedCrossRef Alix-Panabières, C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res. 2008;14:5013–21.PubMedCrossRef
29.
go back to reference 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. 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.
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Circulating Endothelial Cell (CEC) as a Diagnostic and Prognostic Marker in Malignant Pleural Mesothelioma (MPM)
Authors
Kazue Yoneda, BA
Fumihiro Tanaka, MD, PhD
Nobuyuki Kondo, MD, PhD
Hayato Orui, MD
Masaki Hashimoto, MD
Teruhisa Takuwa, MD
Seiji Matsumoto, MD, PhD
Yoshitomo Okumura, MD, PhD
Noriaki Tsubota, MD, PhD
Ayuko Sato, PhD
Tohru Tsujimura, MD, PhD
Kozo Kuribayashi, MD, PhD
Kazuya Fukuoka, MD, PhD
Takashi Nakano, MD, PhD
Seiki Hasegawa, MD, PhD
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 13/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2506-0

Other articles of this Issue 13/2012

Annals of Surgical Oncology 13/2012 Go to the issue