American journal of clinical pathology · 2020
Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver.
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Van Treeck Benjamin J, Lotfalla Mira, Czeczok Thomas W, Mounajjed Taofic, Moreira Roger K, Allende Daniela S, Reid Michelle D, Naini Bita V, Westerhoff Maria, Adsay N Volkan, Kerr Sarah E, I Ilyas Sumera, Smoot Rory L, Liu Yuanhang, Davila Jaime, Graham Rondell P
Аннотация
OBJECTIVES: Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/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-α, 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 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt 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 and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.
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-α, 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 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt 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 and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.
Предметные рубрики MeSH
Biomarkers, TumorCystadenoma, MucinousDNA Mutational AnalysisEstrogensFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHedgehog ProteinsHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryImmunophenotypingLiverLiver NeoplasmsOvarySequence Analysis, DNAStromal CellsWnt Signaling Pathway