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
. 2021 Nov-Dec;24(6):523-530.
doi: 10.1177/10935266211027417. Epub 2021 Jul 15.

Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma

Zahra Alipour  1 , Kris Ann P Schultz  2   3 , Ling Chen  4 , Anne K Harris  2   3 , Ivan A Gonzalez  1   5 , John Pfeifer  1 , D Ashley Hill  6 , Mai He  1 , Louis P Dehner  1
Affiliations

Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma

Zahra Alipour et al. Pediatr Dev Pathol. 2021 Nov-Dec.

Abstract

Introduction: Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB.

Material and methods: Cases were collected from departmental archives and the International PPB/DICER1 Registry. Immunohistochemistry (IHC) for PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) genes were performed. In addition, normal-tumor paired whole exome sequencing (WES) was performed in two cases.

Results: Twenty-five PPB cases were studied, consisting of Type I (n = 8, including 2 Ir), Type II (n = 8) and Type III (n = 9). PD-L1 combined positive score (CPS) of 1, 4 and 80 was seen in three (3/25, 12.0%) cases of Type II PPB with negative staining in the remaining cases. PD-1 and CD8 stains demonstrated positive correlation (P < .05). The density of PD1 and CD8 in the interface area was higher than within tumor (P < .05). The MMR proteins were retained. TMB was 0.65 mutations/Mb in type II PPB with high expression of PD-L1, and 0.94 mutations/Mb in one negative PD-L1 case with metastatic tumor.

Conclusion: A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.

Keywords: DNA mismatch repair; PD-1; PD-L1; pleuropulmonary blastoma; tumor mutation burden; whole exome sequencing.

PubMed Disclaimer

Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS

All authors declare no conflicts of interests.

Figures

Figure 1 -
Figure 1 -
Representative images from primary tumor, case 10. A. Primary tumor of PPB II present in pleura and adhesions of lower right middle lobe, H&E, 200X.
Fig 1B.
Fig 1B.
PD-L1 staining in tumor and immune cells, showing higher staining of immune cells than tumor cells, PD-L1, 200X.
Fig 1C.
Fig 1C.
Higher power showing PD-L1 membranous staining, PD-L1, 400X.
Fig 1D.
Fig 1D.
CD8 and PD1 double staining showing, while most PD1 expression (red) was seen in CD8 T cells (brown), it was also expressed in other cells, CD-8/PD-1 (brown/red), 400X.
See this image and copyright information in PMC

References

    1. The International Pleuropulmonary Blastoma/DICER1 Registry. A very rare disease: enrolling patients in the Registry. 2019. Available at: https://www.ppbregistry.org/health-professionals/critical-issues/a-very-.... Last assessed March 11, 2021.
    1. Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: A report on 350 central pathology–confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015;121(2):276–85. - PMC - PubMed
    1. Aliya N, Husain AN, Stocker JT, Dehner LP. Stocker and Dehner's Pediatric Pathology. 4th ed. Philadelphia. Wolters Kluwer; 2015. Chapter 12, The Respiratory Tract; p. 494–5. ISBN/ISSN 9781451193732.
    1. Hill DA, Ivanovich J, Priest JR, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009;325:965. - PMC - PubMed
    1. Priest JR, Watterson J, Strong L, et al. Pleuropulmonary blastoma: a marker for familial disease. J Pediatr. 1996;128:220–224. - PubMed

Supplementary concepts