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Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM)

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM).

Methods

We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule.

Results

Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523–0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530–5.511; P = 0.001) for epithelioid MPM patients.

Conclusions

CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

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Acknowledgment

We thank Ms. Mayo Yamamoto for assistance in preparation of the manuscript. 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, Japan.”

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Authors and Affiliations

  1. Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan

    Kazue Yoneda PhD, Fumihiro Tanaka MD, PhD, Nobuyuki Kondo MD, PhD, Masaki Hashimoto MD, Teruhisa Takuwa MD, Seiji Matsumoto MD, PhD, Yoshitomo Okumura MD, PhD & Seiki Hasegawa MD, PhD

  2. Second Department of Surgery (Chest Surgery), University of Occupational and Environmental Health, Kitakyusyu, Japan

    Kazue Yoneda PhD & Fumihiro Tanaka MD, PhD

  3. Department of Thoracic Surgery, Itami City Hospital, Itami, Japan

    Yoshitomo Okumura MD, PhD

  4. Department of Thoracic Oncology, Hyogo College of Medicine, Nishinomiya, Japan

    Noriaki Tsubota MD, PhD

  5. Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan

    Ayuko Sato PhD & Tohru Tsujimura MD, PhD

  6. Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    Kazuya Fukuoka MD, PhD, Chiharu Tabata MD, PhD & Takashi Nakano MD, PhD

  7. Department of Respiratory Medicine, Murakami Memorial Hospital, Asahi University, Gifu, Japan

    Kozo Kuribayashi MD, PhD

Authors
  1. Kazue Yoneda PhD
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  2. Fumihiro Tanaka MD, PhD
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  3. Nobuyuki Kondo MD, PhD
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  4. Masaki Hashimoto MD
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  5. Teruhisa Takuwa MD
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  6. Seiji Matsumoto MD, PhD
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  7. Yoshitomo Okumura MD, PhD
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  8. Noriaki Tsubota MD, PhD
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  9. Ayuko Sato PhD
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  10. Tohru Tsujimura MD, PhD
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  11. Kozo Kuribayashi MD, PhD
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  12. Kazuya Fukuoka MD, PhD
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  13. Chiharu Tabata MD, PhD
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  14. Takashi Nakano MD, PhD
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  15. Seiki Hasegawa MD, PhD
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Corresponding author

Correspondence to Fumihiro Tanaka MD, PhD.

Appendix

Appendix

See Tables 1, 2, 3 and 4; Fig. 5.

Table 3 Multivariate analysis of prognostic factors for MPM patients (all histology)
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Table 4 Multivariate analysis of prognostic factors for malignant pleural mesothelioma patients (epithelioid-type patients only)
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Fig. 5
figure 5

Survival curves according to CTC count in nonepithelioid-type MPM patients

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Yoneda, K., Tanaka, F., Kondo, N. et al. Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM). Ann Surg Oncol 21 (Suppl 4), 472–480 (2014). https://doi.org/10.1245/s10434-013-3399-2

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  • DOI: https://doi.org/10.1245/s10434-013-3399-2

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