Pleural effusion TGF-beta is highly diagnostic and prognostic in malignant pleural mesothelioma

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Paul Stockhammer

Citation

Annals of Oncology (2019) 30 (suppl_5): v747-v755. 10.1093/annonc/mdz266

Authors

P. Stockhammer1, T. Ploenes2, M. Schuler3, S. Langer4, C. Aigner2, B. Hegedus2

Author affiliations

  • 1 Thoracic Surgery, Medizinische Universitaet Wien, 1090 - Vienna/AT
  • 2 Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, 45239 - Essen/DE
  • 3 Westdeutsches Tumorzentrum, Westdeutsches Tumorzentrum Essen, 45147 - Essen/DE
  • 4 Fujirebio Germany Gmbh, Fujirebio Germany GmbH, 30173 - Hannover/DE
More

Resources

Background

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy associated with dismal prognosis. In order to support diagnosis and to risk stratify patients, more reliable biomarkers are urgently needed. Emerging evidence suggests a functional role of transforming growth factor-β (TGF-β) in MPM tumorigenesis, however, its clinical implementation remains unknown.

Methods

Pleural effusion samples from 48 consecutively diagnosed MPM patients and 24 patients with non-malignant pleural disease (NMPD) at diagnosis were measured by ELISA for TGF-β and by chemiluminescence enzyme immunoassay for mesothelin (SMRP). In 22 of those MPM and 19 of those NMPD patients, TGF-β and SMRP were also measured in corresponding sera.

Results

Effusion TGF-β levels were significantly higher in MPM patients than in NMPD patients (p < 0.0001), with an AUC of 0.78 (p = 0.0001). Both epithelioid and non-epithelioid MPM patients had significantly higher effusion TGF-β levels than NMPD patients (NMPD vs epithelioid: p < 0.05; NMPD vs non-epithelioid: p < 0.0001) and within the MPM patient cohort elevated effusion TGF-β levels were seen in patients with advanced disease (p < 0.005). Strikingly, patients with high effusion TGF-β levels ( > =14.36ng/mL) had significantly worse overall survival (HR 3.30, p < 0.0005) which was confirmed by a multivariate cox regression model yielding effusion TGF-β and multimodality treatment to be independently prognostic. In contrary, circulating TGF-β was neither diagnostic nor prognostic and did not correlate with matched effusion TGF-β. Of note, effusion SMRP performed similar to effusion TGF-β as diagnostic marker (AUC: 0.71, p = 0.005), but was only elevated in epithelioid tumors and not prognostic in our MPM cohort. However, there was a significant negative correlation between effusion TGF-β and SMRP and by combining both biomarkers we could remarkably increase sensitivity to 93.4%.

Conclusions

Our data is the first evidence showing pleural effusion TGF-β to be a novel highly diagnostic and prognostic biomarker in MPM applicable for epithelioid and non-epithelioid MPM. Those findings may pave the way for future clinical trials targeting TGF-β in MPM and beyond.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Langer: Full / Part-time employment, Employed at Fujirebio Germany, which provided non-financial support in terms of SMRP measurements: Fujirebio Germany GmbH. All other authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings