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

BMC Cancer

Krishna B Sriram¹  Vandana Relan¹  Belinda E Clarke³  Edwina E Duhig³  Morgan N Windsor²  Kevin S Matar²  Rishendran Naidoo²  Linda Passmore¹  Elizabeth McCaul¹  Deborah Courtney¹  Ian A Yang¹  Rayleen V Bowman¹  Kwun M Fong¹ 

[1] Department of Thoracic Medicine, The Prince Charles Hospital, Queensland, Australia

[2] Department of Thoracic Surgery, The Prince Charles Hospital, QLD, Australia

[3] Department of Anatomical Pathology, The Prince Charles Hospital, Queensland, Australia

关键词: Mesothelin;    DNA integrity index;    Lung cancer;    Mesothelioma;    Malignant pleural effusions;   

Others  :  1080181
DOI  :  10.1186/1471-2407-12-428

 received in 2012-01-02, accepted in 2012-09-23,  发布年份 2012

【 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.

【 授权许可】

   
2012 Sriram et al.; licensee BioMed Central Ltd.

【 图 表 】

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