Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM)

Our plain-English summary of Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM), by K. Yoneda, F. Tanaka, N. Kondo, et al (Annals of Surgical Oncology, 2012).

The study

• Authors: K. Yoneda, F. Tanaka, N. Kondo, H. Orui, M. Hashimoto, T. Takuwa, S. Matsumoto, Y. Okumura, N. Tsubota, A. Sato, T. Tsujimura, K. Kuribayashi, K. Fukuoka, T. Nakano, S. Hasegawa
• Journal: Annals of Surgical Oncology
• Published: 2012;19(13):4229-37
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This prospective study at Hyogo College of Medicine in Japan tested whether a blood count of circulating endothelial cells (CECs) could help diagnose malignant pleural mesothelioma and predict survival. CECs are cells shed from blood-vessel walls. From September 2007 through November 2009, 110 patients suspected of having mesothelioma were enrolled. After pleural biopsy, 79 had mesothelioma and 30 had nonmalignant pleural disease. One patient with lung cancer was excluded. Most patients had a history of asbestos exposure. The mean CEC count per 4.0 mL of blood was 120.3 in mesothelioma patients and 39.9 in nonmalignant patients. At a cutoff of 50 cells per 4.0 mL, sensitivity was 49.4% and specificity 76.7%. The authors said the test alone was not enough for diagnosis. Among mesothelioma patients, median overall survival was 11.4 months (95% CI 7.6 to 15.2) for counts above 50 versus 20.1 months (95% CI 16.0 to 24.2) for lower counts (P = 0.028). In multivariate analysis, higher counts had a hazard ratio of 2.24 (95% CI 1.24 to 4.43). The authors concluded CEC was a promising marker but needs validation studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective diagnostic and prognostic study of a blood test (CEC count) in patients undergoing pleural biopsy for suspected mesothelioma
• Who was studied: 110 consecutive patients with suspected malignant pleural mesothelioma on CT and PET scanning, enrolled at Hyogo College of Medicine Hospital, Japan, from September 2007 through November 2009. One patient was excluded because biopsy showed lung adenocarcinoma. Of the 109 eligible patients, 79 had malignant pleural mesothelioma and 30 had nonmalignant pleural diseases.
• Exposure: The measurement studied was the CEC count in 4.0 mL of blood, captured with an anti-CD146 antibody. Asbestos exposure was recorded only as a patient characteristic: 26 of 30 nonmalignant patients (87%) and 72 of 79 mesothelioma patients (91%) had a history of exposure (Table 1). No fiber types, products, jobs or doses were described.
• Main results:
  • Mean CEC count per 4.0 mL of peripheral blood was 120.3 in mesothelioma patients and 39.9 in nonmalignant patients (P = 0.001).
  • For telling mesothelioma apart from nonmalignant disease, the area under the ROC curve was 0.700 (95% CI 0.595 to 0.806; P = 0.001).
  • At the cutoff of 50 cells per 4.0 mL: sensitivity 49.4%, specificity 76.7%, positive predictive value 84.8%, negative predictive value 36.5%.
  • In the 38 mesothelioma patients whose tumor microvessel density could be evaluated, CEC count correlated positively with it (r = 0.444; P = 0.001).
  • Among mesothelioma patients, CEC count did not differ significantly by histologic subtype or clinical stage. The mean was 151.8 in stage IV versus 80.6 in stages I to III (P = 0.190).
  • Median overall survival was 11.4 months (95% CI 7.6 to 15.2) for mesothelioma patients with CEC count above 50 per 4.0 mL (n = 39), versus 20.1 months (95% CI 16.0 to 24.2) for those with lower counts (n = 40); P = 0.028.
  • In multivariate analysis of mesothelioma patients, three factors were independent predictors of poor prognosis: higher CEC count (HR 2.24, 95% CI 1.24 to 4.43), poor performance status (HR 3.07, 1.78 to 5.29) and nonepithelioid histology (HR 2.45, 1.15 to 5.20).
• The authors' conclusion: The authors concluded that CEC, as a surrogate of tumor angiogenesis, was a promising marker for diagnosing malignant pleural mesothelioma and predicting prognosis, and that future validation studies should be conducted.
• Limitations the authors state:
  • Sensitivity at the cutoff of 50 was only 49.4%, so the authors stated the CEC test alone is not enough for diagnosis.
  • The correlation with microvessel density was significant but not strong. The authors suggested that density measured with one CD34 antibody in a small biopsy may not represent the whole tumor.
  • The study did not show a significant increase in CEC count with more advanced clinical stage.
  • The authors stated that future validation studies are needed to establish the prognostic significance of CEC.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Angiogenesis, confidence interval, Prognosis, Median Overall Survival, Multivariate Analysis, Hazard Ratio.

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• EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' — Y. Chikaishi, K. Yoneda, et al. (2017)

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