Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia

Author(s)

St Laurent, Jessica D. ^{[1, 2]} ; Lin, Lawrence H. ^{[3, 4]} ; Owen, David M. ^[5] ; Maesta, Izildinha ^[6] ; Castaneda, Arnold ^[2] ; Hasselblatt, Kathleen T. ^[2] ; Goldstein, Donald P. ^[2] ; Horowitz, Neil S. ^[2] ; Berkowitz, Ross S. ^[2] ; Elias, Kevin M. ^{[1, 2]}

Affiliation

^[1] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 - USA

^[2] Harvard Med Sch, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Onc, 75 Francis St, Boston, MA 02115 - USA

^[3] Univ Sao Paulo, Trophoblast Dis Ctr, Med Sch, Sao Paulo - Brazil

^[4] New York Univ Langone Hlth, Dept Pathol, New York, NY - USA

^[5] Univ Texas Southwestern Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 - USA

^[6] Sao Paulo State Univ UNESP, Sao Paulo State Univ, Clin Hosp Botucatu Med Sch, Botucatu Trophoblast Dis Ctr, Botucatu, SP - Brazil

• Document type: Journal article
• Source: REPRODUCTIVE SCIENCES; v. 28, n. 11, p. 3200-3211, NOV 2021.
• Web of Science Citations: 1

Abstract

To investigate if differences in imprinting at tropho-microRNA (miRNA) genomic clusters can distinguish between pre-gestational trophoblastic neoplasia cases (pre-GTN) and benign complete hydatidiform mole (CHM) cases at the time of initial uterine evacuation. miRNA sequencing was performed on frozen tissue from 39 CHM cases including 9 GTN cases. DIO3, DLK1, RTL1, and MEG 3 mRNA levels were assessed by qRT-PCR. Protein abundance was assessed by Western blot for DIO3, DLK1, and RTL1. qRT-PCR and Western blot were performed for selenoproteins and markers of oxidative stress. Immunohistochemistry (IHC) was performed for DIO3 on an independent validation set of clinical samples (n = 42) and compared to normal placenta controls across gestational ages. Relative expression of the 14q32 miRNA cluster was lower in pre-GTN cases. There were no differences in protein abundance of DLK1 or RTL1. Notably, there was lower protein expression of DIO3 in pre-GTN cases (5-fold, p < 0.03). There were no differences in mRNA levels of DIO3, DLK1, RTL1 or MEG 3. mRNA levels were higher in all CHM cases compared to normal placenta. IHC showed syncytiotrophoblast-specific DIO3 immunostaining in benign CHM cases and normal placenta, while pre-GTN cases of CHM lacked DIO3 expression. We describe two new biomarkers of pre-GTN CHM cases: decreased 14q32 miRNA expression and loss of DIO3 expression by IHC. Differences in imprinting between benign CHM and pre-GTN cases may provide insight into the fundamental development of CHM. (AU)

• FAPESP's process: 20/08830-6 - Elucidating the effect of epigenetic modifications of complete hydatidiform mole microRNA signalling and risk of malignization
• Grantee: Izildinha Maestá
• Support type: Regular Research Grants