Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver

Abstract

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.

Mesenteric and Retroperitoneal Mucinous Cystic Neoplasms: A Case Series

“…Recently, our group showed that ovarian-type stroma in MCN of the liver expresses markers and enzymes of steroidogenesis raising the possibility that the stroma produces hormones locally. 20 The identification of expression of SF-1 in the current series raises the same possibility for MCN of the mesentery and retroperitoneum.…”

“…21 Others have suggested that MCN of the pancreas arises from aberrant migration of primordial germ cells into the embryologic dorsal mesentery which forms the neck and body of the pancreas en route to the ovaries. 22-24 In our prior work, 20 we raise the possibility that both hypotheses may be true and the primitive cells may migrate into the pancreas and contribute to the periductal fetal mesenchyme around developing pancreatic ducts. The identification of MCNs within the retroperitoneum and mesentery with this distribution wherein the tumors follow the route of the dorsal mesentery from the central retroperitoneum to the right iliac fossa adds support to the hypothesis that the origin of MCN is related to the dorsal mesentery.…”

Intralobular distribution of ovarian-like stroma in pancreatic mucinous cystic neoplasms: a discussion on its tumorigenesis

“…Using immunohistochemistry, nuclear expression of β-catenin for OLS was observed for all MCN cases and all OLS sites. Several studies have suggested the activation of Wnt signaling pathway in OLS and its contribution to MCN development 15 – 17 . Sano et al have shown the activation of Wnt signaling pathway in OLS by introducing Wnt1 and KRAS G12D to the epithelial component in mice 15 .…”

“…Sano et al have shown the activation of Wnt signaling pathway in OLS by introducing Wnt1 and KRAS G12D to the epithelial component in mice 15 . Fukushima et al have shown the overexpression of Wnt2B and secreted frizzled-related protein , a moderator of Wnt pathway in OLS 16 and Treek et al have shown the upregulation of Wnt and the Hedgehog pathway in OLS 17 . This is in line with our result that all OLS showed nuclear accumulation of β-catenin irrespective of cyst size or OLS site and suggests consistent activation of Wnt pathway for OLS.…”

Eco-Friendly Control of Culex quinquefasciatus Say (Diptera: Culicidae) through Botanical Insecticides and Predatory Insects

“…Co-Expression of SATB2 and CK20 in Mucinous Ovarian Tumors staining is needed, tissue depletion will limit the number of staining that can be performed. Therefore, it is important to use immunohistochemical staining effectively to determine the origin site, without unnecessary staining to increase the hospital cost of patients (Van Treeck et al, 2020). While many immunostaining or different combinations of immunostaining have been studied previously, including CK7, CK20, villin, CDX2, PAX8 and ER, the coexpression of mucinous ovarian tumors SATB2 and CK20 and its association with tumor pathological classification and prognostic outcome have not been reported.…”