Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas

被引：50

作者：

Sriram, Krishna B. ^{[1
,2
]}

Relan, Vandana ^{[1
,2
]}

Clarke, Belinda E. ^{[3
]}

Duhig, Edwina E. ^{[3
]}

Windsor, Morgan N. ^{[4
]}

Matar, Kevin S. ^{[4
]}

Naidoo, Rishendran ^{[4
]}

Passmore, Linda ^{[1
,2
]}

McCaul, Elizabeth ^{[1
,2
]}

Courtney, Deborah ^{[1
,2
]}

Yang, Ian A. ^{[1
,2
]}

Bowman, Rayleen V. ^{[1
,2
]}

Fong, Kwun M. ^{[1
,2
]}

机构：

[1] Univ Queensland, Sch Med, UQ Thorac Res Ctr, Brisbane, Qld 4072, Australia

[2] Prince Charles Hosp, Dept Thorac Med, Brisbane, Qld, Australia

[3] Prince Charles Hosp, Dept Anat Pathol, Brisbane, Qld, Australia

[4] Prince Charles Hosp, Dept Thorac Surg, Brisbane, Qld, Australia

来源：

BMC CANCER | 2012年 / 12卷

基金：

英国医学研究理事会;

关键词：

Malignant pleural effusions; Mesothelioma; Lung cancer; DNA integrity index; Mesothelin; FREE CIRCULATING DNA; FREE PLASMA DNA; CANCER-PATIENTS; LUNG-CANCER; QUANTITATIVE-ANALYSIS; SOLUBLE MESOTHELIN; DIAGNOSTIC MARKER; PROSTATE-CANCER; NUCLEIC-ACIDS; SERUM;

D O I：

10.1186/1471-2407-12-428

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE. Methods: We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA. Results: Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively). Conclusion: Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.

引用

页数：12

共 41 条

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