Molecular Profiling of Malignant Pleural Effusions with Next Generation Sequencing (NGS): Evidence that Supports Its Role in Cancer Management.

Georgia Ι. Grigoriadou,Stepan M. Esagian,Ilias P. Nikas,Han Suk Ryu

doi:10.3390/jpm10040206

Abstract

Malignant pleural effusions (MPEs) often develop in advanced cancer patients and confer significant morbidity and mortality. In this review, we evaluated whether molecular profiling of MPEs with next generation sequencing (NGS) could have a role in cancer management, focusing on lung cancer. We reviewed and compared the diagnostic performance of pleural fluid liquid biopsy with other types of samples. When applied in MPEs, NGS may have comparable performance with corresponding tissue biopsies, yield higher DNA amount, and detect more genetic aberrations than blood-derived liquid biopsies. NGS in MPEs may also be preferable to plasma liquid biopsy in advanced cancer patients with a MPE and a paucicellular or difficult to obtain tissue/fine-needle aspiration biopsy. Of interest, post-centrifuge supernatant NGS may exhibit superior results compared to cell pellet, cell block or other materials. NGS in MPEs can also guide clinicians in tailoring established therapies and identifying therapy resistance. Evidence is still premature regarding the role of NGS in MPEs from patients with cancers other than lung. We concluded that MPE processing could provide useful prognostic and theranostic information, besides its diagnostic role.

Highlights

Pleural effusion (PE), the pathologic accumulation of excess fluid inside the pleural cavity, is a complication that often appears in a wide spectrum of clinical settings
Yang et al and Villatoro et al were able to isolate these mutations from malignant pleural effusions (MPEs) of patients with disease progression after first-line treatment with tyrosine kinase inhibitors (TKIs)
Tong et al found that there was no difference in the progression-free survival of 10 patients, when treatment decision with TKI was based on pleural fluid supernatant rather than tissue analysis [37]

Summary

Introduction

Pleural effusion (PE), the pathologic accumulation of excess fluid inside the pleural cavity, is a complication that often appears in a wide spectrum of clinical settings. The cell pellet is subsequently used to form diverse preparations including direct smears, cytospins, liquid-based cytology (LBC) slides and/or formalin-fixed paraffin-embedded (FFPE) cell blocks; these are stained and evaluated morphologically to formulate a diagnosis [2,9] Ancillary techniques such as Immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) are routinely applied on any of the aforementioned preparations to solve selective diagnostic issues—e.g., metastatic adenocarcinoma vs mesothelioma differential diagnosis; confirmation of the primary malignancy site or provide clinically relevant prognostic and predictive information; examples of the latter include HER2 testing in breast cancer and PD-L1 testing to initiate immunotherapy [2,9,10]. The latter comprise an optimal material for analysis techniques such as PCR and sequencing, while molecular testing can successfully be performed on all previously mentioned cell pellet-based preparations besides effusion supernatants [2,8,9,10,11]

Results

Discussion

Conclusion