Molecular and immunohistochemical analysis of mucinous cystic neoplasm of the liver

Abstract

Objectives: Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous andl or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied Methods: Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. Results: Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-alpha, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of I 7 beta-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Win pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. Conclusions: Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue andl or stromal cells with capacity to transdifferentiate to ovarian cortical cells.