PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.
Am J Surg Pathol
; 48(6): 681-690, 2024 Jun 01.
Article
de En
| MEDLINE
| ID: mdl-38682454
ABSTRACT
Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes:
34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3LCN1 fusion. In addition, the HTN3MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3LCN1 and HTN3MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs des glandes salivaires
/
Marqueurs biologiques tumoraux
/
Carcinome à cellules acineuses
/
Membre-2 du groupe A de la sous-famille-4 de récepteurs nucléaires
Limites:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Am J Surg Pathol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine