Document Detail

Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.
MedLine Citation:
PMID:  23050525     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker.
METHODS: We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay.
RESULTS: Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos-exposed persons as compared with 48 patients with mesothelioma.
CONCLUSIONS: Plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can further differentiate mesothelioma effusions from other malignant and benign effusions. (Funded by the Early Detection Research Network, National Institutes of Health, and others.).
Harvey I Pass; Stephen M Levin; Michael R Harbut; Jonathan Melamed; Luis Chiriboga; Jessica Donington; Margaret Huflejt; Michele Carbone; David Chia; Lee Goodglick; Gary E Goodman; Mark D Thornquist; Geoffrey Liu; Marc de Perrot; Ming-Sound Tsao; Chandra Goparaju
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  367     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  2012-10-23     Revised Date:  2014-08-06    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1417-27     Citation Subset:  AIM; IM    
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MeSH Terms
Asbestos* / adverse effects
Biological Markers / blood
Case-Control Studies
Diagnosis, Differential
Extracellular Matrix Proteins / blood*
Kaplan-Meier Estimate
Mesothelioma / blood,  diagnosis*
Middle Aged
Occupational Exposure*
Pleural Effusion / blood,  diagnosis
Pleural Effusion, Malignant / blood,  diagnosis
Pleural Neoplasms / blood,  diagnosis*
ROC Curve
Sensitivity and Specificity
Grant Support
P30 CA016087/CA/NCI NIH HHS; U01 CA-111295/CA/NCI NIH HHS; U01 CA-113913/CA/NCI NIH HHS; U01 CA111295/CA/NCI NIH HHS; U01 CA113913/CA/NCI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/EFEMP1 protein, human; 0/Extracellular Matrix Proteins; 1332-21-4/Asbestos
Comment In:
N Engl J Med. 2013 Jan 10;368(2):190   [PMID:  23301743 ]
N Engl J Med. 2013 Jan 10;368(2):189-90   [PMID:  23301745 ]
N Engl J Med. 2013 Jan 10;368(2):189   [PMID:  23301744 ]
Erratum In:
N Engl J Med. 2012 Nov;367(18):1768

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