Diagnostic performance of CTLA-4, carcinoembryonic antigen and CYFRA 21-1 for malignant pleural effusion

The diagnosis of malignant pleural effusion (MPE) remains a clinical challenge. As a negative regulator of T-cell activation, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has been associated with many malignant diseases. However, there is limited data about the relationship between CTLA-4 and MPE. The present study aims to investigate whether CTLA-4 levels may correlate with presence of MPE and to assess its potential diagnostic accuracy relative to that of the established markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1).

Pleural effusion samples were collected from 36 patients with MPE and 48 patients with benign pleural effusion (BPE). Pleural levels of CTLA-4 were measured by ELISA; levels of CEA and CYFRA 21-1, by electrochemiluminescence immunoassay. Receiver operating characteristic curves were calculated to evaluate the ability of CTLA-4, CEA and CYFRA 21-1 to differentiate MPE from BPE.

Pleural levels of CTLA-4 were significantly higher in MPE than in BPE patients (471.73 ± 378.86 vs. 289.22 ± 173.67 pg/ml, p = 0.004). At a cut-off value of 351.25 pg/ml, the sensitivity and specificity of CTLA-4 in diagnosing MPE were 58.30% and 83.30%, respectively, and the area under the curve was 0.72. Pleural levels of CEA and CYFRA 21-1 were also higher in MPE. Using the combination of CTLA-4, CEA and CYFRA 21-1 increased diagnostic sensitivity to 88.89% and the area under the curve to 0.92.

The results of this preliminary study suggest that increased levels of CTLA-4 correlate with MPE, and that CTLA-4 may have some diagnostic usefulness when used in combination with conventional tumor markers such as CEA and CYFRA 21-1. These results justify larger, more rigorous studies to validate our findings.