Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver
| Autor: | N. Volkan Adsay, Sarah E. Kerr, Thomas W Czeczok, Rory L. Smoot, Taofic Mounajjed, Roger K. Moreira, Michelle D. Reid, Benjamin J. Van Treeck, Daniela S. Allende, Mira M Lotfalla, Rondell P. Graham, Maria Westerhoff, Bita V. Naini, Jaime I. Davila, Sumera Rizvi, Yuanhang Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Stromal cell medicine.drug_class DNA Mutational Analysis Estrogen receptor Biology Immunophenotyping 03 medical and health sciences 0302 clinical medicine Stroma Downregulation and upregulation Cystadenoma Mucinous medicine Biomarkers Tumor Humans Hedgehog Proteins Wnt Signaling Pathway Gene Expression Profiling Liver Neoplasms Ovary Wnt signaling pathway High-Throughput Nucleotide Sequencing Estrogens General Medicine Sequence Analysis DNA Original Articles Immunohistochemistry Cystic Neoplasm Gene Expression Regulation Neoplastic 030104 developmental biology Liver Estrogen 030220 oncology & carcinogenesis Female Stromal Cells |
| Zdroj: | Am J Clin Pathol |
| ISSN: | 1943-7722 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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