Diagnostic implications of telomerase activity in pleural effusions

To the Editor:

In a recent issue of the European Respiratory Journal, Dikmen et al. 1 analysed the diagnostic efficacy of telomerase activity in pleural fluid for distinguishing between benign and malignant effusions. They found that the sensitivity and specificity of telomerase activity for diagnosing malignancy was 82 and 80%, respectively. With these data the authors concluded that telomerase activity is a highly sensitive diagnostic biomarker for malignancy and may be used as an adjunct to cytological findings in determining malignant pleural effusions. However, in our opinion, this affirmation can not be applied to clinical practice.

Sensitivity and specificity are important points in the study of the diagnostic value of a test. However, from a clinical point of view, other measures of diagnostic accuracy are of great interest 2, i.e. likelihood ratios and predictive values. Likelihood ratios are the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that the same result would be expected in a patient without the target disorder, and predictive values are the post-test probability 3, 4. We calculated these measures using the data reported by Dikmen et al. 1, and obtained positive and negative likelihood ratios of 4.1 and 0.22, respectively, which are of modest diagnostic interest 3, 4. The positive predictive value, in this case, represents the probability that a patient has a malignant pleural effusion if telomerase activity is detected in the pleural fluid. Although it obviously depends on pre-test probability, this predictive value is very low, especially when the prevalence (pre-test probability) is ∼20–30%, as is usually observed in general hospitals (table 1⇓) 5. These findings are similar to those obtained when using classical tumour markers 5.

In our experience 6, the determination of C‐reactive protein (CRP) in pleural exudates, which is an inexpensive test and easy to perform, would be of greater interest. A low CRP level (<20 mg·L⁻¹) has a better positive likelihood ratio and positive predictive value for diagnosing malignancy than those of telomerase activity, with the additional advantage that a level >45 mg·L⁻¹ virtually rules out this possibility.

In conclusion, we consider that the measurement of telomerase activity in pleural fluid adds little to the diagnostic work-up of a pleural effusion and should not be used as an adjunct finding in determining malignancy.