Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 2;13(23):7322.
doi: 10.3390/jcm13237322.

Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma

Oliver Illini  1   2 , Michal Benej  3   4 , Anna Sophie Lang-Stöberl  2 , Hannah Fabikan  2 , Luka Brcic  5 , Florian Sucher  5 , Dagmar Krenbek  6 , Tibor Krajc  3   4 , Christoph Weinlinger  2 , Maximilian J Hochmair  1   2 , Arschang Valipour  1   2 , Thomas Klikovits  3   4 , Stefan Watzka  3   4   7
Affiliations

Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma

Oliver Illini et al. J Clin Med. .

Abstract

Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.

Keywords: BAP-1; ILK; PD-L1; multimodality treatment; pleural mesothelioma; prognostic biomarkers.

PubMed Disclaimer

Conflict of interest statement

Illini O. received speaker fees and honoraria for advisory boards from Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Menarini, Merck Sharp and Dohme, Pfizer, and Roche. Received research grants from Amgen and AstraZeneca outside of the submitted study. Benej M. declares that there is no conflict of interest. Klikovits T. received speaker fees and honoraria for advisory boards from AstraZeneca, BMS, MSD, Roche and Medtronic. Lang-Stöberl A.S. declares that there is no conflict of interest. Fabikan H. declares that there is no conflict of interest. Brcic L. reports personal fees for lectures, consultancy and participation in advisory boards from AstraZeneca, Bristol Myers Squibb, Johnson and Johnson, Merck, Lilly Oncology, Roche, MSD, Pfizer and Takeda Oncology. Sucher F. declares that there is no conflict of interest. Krenbek D. received speaker fees and/or honoraria for advisory boards from Eli Lilly, Merck Sharp and Dohme, Pfizer, and Roche. Weinlinger C. declares that there is no conflict of interest. Hochmair M. reports personal fees for lectures, consultancy and participation in advisory boards from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Lilly Oncology, Roche, MSD, Pfizer and Takeda Oncology. Valipour A. reports personal fees for lectures, consultancy and participation in advisory boards from Astra Zeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Merck, MSD, Pfizer, Roche, Takeda, and Zentiva outside of the submitted study. Watzka S. reports speaker fees from AstraZeneca, Bristol-Myers Squibb and Merck Sharp and Dohme. During the preparation of this work, no AI or AI-assisted technologies were used.

Figures

Figure 1
Figure 1
(A) Positive reaction of mesothelioma cells to antibody against PD-L1 with few positive lymphocytes (asterisk); (B) Loss of nuclear staining in mesothelioma cells with unspecific granular cytoplasmic reaction and clearly positive nuclear staining of lymphocytes (positive internal control); (C) Positive reaction of mesothelioma cells to antibody against ILK; (Objective ×20, immunohistochemistry). The blue bar indicates 100 µm.
Figure 2
Figure 2
Treatment received by 52 patients with PM. PM, pleural mesothelioma; CHT, chemotherapy; IO, immunotherapy; RT, radiotherapy.
Figure 3
Figure 3
Expression of PD-L1 TPS and CPS, BAP-1 loss and ILK in patients with PM. CPS, combined positive score; PM, pleural mesothelioma; PD-L1, programmed cell death ligand 1; TPS, tumor proportion score.
Figure 4
Figure 4
Kaplan–Meier estimates for OS according to PD-L1 TPS (A), PD-L1 CPS (B), BAP-1 loss (C) and ILK (D) in all patients. OS, overall survival; PD-L1, programmed cell death ligand 1; TPS, tumor proportion score; CPS, combined positive score; ILK, integrin-linked kinase.
Figure 5
Figure 5
Kaplan–Meier estimates for OS according to PD-L1 TPS (A), PD-L1 CPS (B), BAP-1 loss (C) and ILK (D) in 27 patients with PM undergoing MMT. OS, overall survival; PD-L1, programmed cell death ligand 1; TPS, tumor proportion score; CPS, combined positive score; ILK, integrin-linked kinase.
See this image and copyright information in PMC

References

    1. Marinaccio A., Binazzi A., Di Marzio D., Scarselli A., Verardo M., Mirabelli D., Gennaro V., Mensi C., Riboldi L., Merler E., et al. Pleural malignant mesothelioma epidemic: Incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int. J. Cancer. 2012;130:2146–2154. doi: 10.1002/ijc.26229. - DOI - PubMed
    1. Wadowski B., De Rienzo A., Bueno R. The Molecular Basis of Malignant Pleural Mesothelioma. Thorac. Surg. Clin. 2020;30:383–393. doi: 10.1016/j.thorsurg.2020.08.005. - DOI - PMC - PubMed
    1. Huang J., Chan S.C., Pang W.S., Chow S.H., Lok V., Zhang L., Lin X., Lucero-Prisno D.E., Xu W., Zheng Z.-J., et al. Global Incidence, Risk Factors, and Temporal Trends of Mesothelioma: A Population-Based Study. J. Thorac. Oncol. 2023;18:792–802. doi: 10.1016/j.jtho.2023.01.095. - DOI - PubMed
    1. Alpert N., van Gerwen M., Taioli E. Epidemiology of mesothelioma in the 21st century in Europe and the United States, 40 years after restricted/banned asbestos use. Transl. Lung Cancer Res. 2020;9:S28–S38. doi: 10.21037/tlcr.2019.11.11. - DOI - PMC - PubMed
    1. Bianchi C., Giarelli L., Grandi G., Brollo A., Ramani L., Zuch C. Latency periods in asbestos-related mesothelioma of the pleura. Eur. J. Cancer Prev. Off. J. Eur. Cancer Prev. Organ. ECP. 1997;6:162–166. - PubMed

LinkOut - more resources