Estrogen Receptor Expression in DICER1-related Lesions is Associated with the Presence of Cystic Components

Paul Scott Thorner; Anne-Laure Chong; Maria Apellaniz-Ruiz; Naciba Benlimame; Paula Marrano; Fadi Brimo; Somruetai Shuangshoti; Shanop Shuangshoti; William D Foulkes

doi:10.1097/PAS.0000000000002209

Estrogen Receptor Expression in DICER1-related Lesions is Associated with the Presence of Cystic Components

Am J Surg Pathol. 2024 Mar 28. doi: 10.1097/PAS.0000000000002209. Online ahead of print.

Authors

Paul Scott Thorner¹, Anne-Laure Chong^{2

3}, Maria Apellaniz-Ruiz^{3

4

5}, Naciba Benlimame⁶, Paula Marrano⁷, Fadi Brimo⁸, Somruetai Shuangshoti⁹, Shanop Shuangshoti¹⁰, William D Foulkes^{2

3

4

5}

Affiliations

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
² Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, Canada.
³ Cancer Axis, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada.
⁴ Department of Human Genetics, McGill University, Montreal, Canada.
⁵ Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec.
⁶ Research Pathology Facility, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.
⁷ Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto.
⁸ Department of Pathology, McGill University Health Centre, Montreal, QC, Canada.
⁹ Institute of Pathology, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand.
¹⁰ Department of Pathology and Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

PMID: 38539053
DOI: 10.1097/PAS.0000000000002209

Abstract

DICER1 tumor predisposition syndrome results from pathogenic variants in DICER1 and is associated with a variety of benign and malignant lesions, typically involving kidney, lung, and female reproductive system. Over 70% of sarcomas in DICER1 tumor predisposition syndrome occur in females. Notably, pediatric cystic nephroma (pCN), a classic DICER1 tumor predisposition syndrome lesion, shows estrogen receptor (ER) expression in stromal cells. There are also renal, hepatic, and pancreatic lesions unassociated with DICER1 tumor predisposition syndrome that have an adult female predominance and are characterized/defined by ER-positive stromal cells. Except for pCN, the expression of ER in DICER1-associated lesions remains uninvestigated. In the present study, ER expression was assessed by immunohistochemistry in 89 cases of DICER1-related lesions and 44 lesions lacking DICER1 pathogenic variants. Expression was seen in stromal cells in pCN and pleuropulmonary blastoma (PPB) types I and Ir, whereas anaplastic sarcoma of kidney and PPB types II and III were typically negative, as were other solid tumors of non-Müllerian origin. ER expression was unrelated to the sex or age of the patient. Expression of ER showed an inverse relationship to preferentially expressed antigen in melanoma (PRAME) expression; as lesions progressed from cystic to solid (pCN/anaplastic sarcoma of kidney, and PPB types I to III), ER expression was lost and (PRAME) expression increased. Thus, in DICER1 tumor predisposition syndrome, there is no evidence that non-Müllerian tumors are hormonally driven and antiestrogen therapy is not predicted to be beneficial. Lesions not associated with DICER1 pathogenic variants also showed ER-positive stromal cells, including cystic pulmonary airway malformations, cystic renal dysplasia, and simple renal cysts in adult kidneys. ER expression in stromal cells is not a feature of DICER1 perturbation but rather is related to the presence of cystic components.