Histone H3 trimethylation on lysine 27 immunostaining pattern in DICER1-associated tumors

Murad Alturkustani; Bo Yang; Crystal Bockoven; Roshan Mahabir; Nick Shillingford; Ryan J Schmidt; Shengmei Zhou; Mikako Warren; David M Parham; Bruce Pawel; Larry L Wang

doi:10.21037/tp-24-61

Histone H3 trimethylation on lysine 27 immunostaining pattern in DICER1-associated tumors

Transl Pediatr. 2024 Apr 30;13(4):624-633. doi: 10.21037/tp-24-61. Epub 2024 Apr 28.

Authors

Murad Alturkustani^#^{1

2

3

4}, Bo Yang^#^{1

5}, Crystal Bockoven^{1

2}, Roshan Mahabir^{1

2}, Nick Shillingford^{1

2}, Ryan J Schmidt^{1

2}, Shengmei Zhou^{1

2}, Mikako Warren^{1

2}, David M Parham^{1

2

3

4

5}, Bruce Pawel^{1

2}, Larry L Wang^{1

2}

Affiliations

¹ Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
² Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ University of Western Ontario, London, ON, Canada.
⁵ Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

^# Contributed equally.

Abstract

Background: DICER1-associated tumors are heterogeneous and affect several organs. DICER1-associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry.

Methods: We explored the H3K27me3 immunostaining pattern in other DICER1-associated tumors. Twelve tumors from eleven patients with confirmed DICER1 mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody.

Results: The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of DICER1-associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One DICER1-associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining.

Conclusions: H3K27me3 expression is not universally lost in DICER1-associated tumors and thus is not predictive of DICER1 mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to DICER1-associated intracranial sarcoma.

Keywords: DICER1; Sertoli-Leydig cell tumor; histone H3 trimethylation on lysine 27 (H3K27me3); immunohistochemistry; pleuropulmonary blastoma (PPB).