An estimated 150 000 patients develop a pleural effusion each year in the UK. Establishing the aetiology of pleural effusions can be challenging as they can be associated with over 50 systemic or pulmonary disorders.¹ Exudative pleural fluids arise from plasma extravasation and contain proteins and cells from the systemic circulation, as well as those released locally from the pleura. This milieu of cellular products potentially holds vital clues that can unveil the underlying cause of the effusion. Decoding these clues has been a long and slow journey,² and only in recent years have several disease-specific pleural fluid markers been incorporated into clinical practice (eg, adenosine deaminase for tuberculous pleuritis³ and brain natriuretic peptide for effusions from cardiac failure).

It is logical that diagnostic clues for mesothelioma, a primary pleural malignancy, would rest within the pleural fluid. The incidence of mesothelioma is rising significantly in the UK and other European countries. Most patients with mesothelioma present with a pleural effusion, and this diagnosis should be considered in all patients with exudative effusions. However, fluid cytology has a notoriously low diagnostic yield, as differentiating mesothelioma cells from benign (or reactive) mesothelial cells is difficult. More invasive procedures such as thoracoscopy for tissue biopsy samples are frequently required.⁴

Finding a diagnostic marker for mesothelioma is a challenging endeavour.⁵ This is made difficult by the heterogeneity of mesothelioma, which comprises various histological subtypes (eg, epithelioid, sarcomatoid, desmoplastic) with dissimilar gene expression patterns,⁶ phenotypes and biological features.⁴ No unique molecule has been shown to reliably define mesothelioma from benign mesothelium or metastatic carcinomas, even by profiling the expression of tens of thousands of genes on mesothelioma tissues using microarray technology.⁷

SOLUBLE MESOTHELIN IN MESOTHELIOMA

The …