TY - JOUR
T1 - Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma
AU - Alipour, Zahra
AU - Schultz, Kris Ann P.
AU - Chen, Ling
AU - Harris, Anne K.
AU - Gonzalez, Ivan A.
AU - Pfeifer, John
AU - Hill, D. Ashley
AU - He, Mai
AU - Dehner, Louis P.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by the Department of Pathology and Immunology faculty development fund to Dr. MH and Dr. LPD, Washington University in St. Louis School of Medicine. Ms. Marina Platik expertly performed the immunohistochemical stains.
Publisher Copyright:
© 2021, Society for Pediatric Pathology All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - DNA mismatch repair
KW - PD-1
KW - PD-L1
KW - pleuropulmonary blastoma
KW - tumor mutation burden
KW - whole exome sequencing
UR - https://www.scopus.com/pages/publications/85110275058
U2 - 10.1177/10935266211027417
DO - 10.1177/10935266211027417
M3 - Article
C2 - 34266329
AN - SCOPUS:85110275058
SN - 1093-5266
VL - 24
SP - 523
EP - 530
JO - Pediatric and Developmental Pathology
JF - Pediatric and Developmental Pathology
IS - 6
ER -