SIN3-HDAC complex-associated factor, a chromatin remodelling gene located in the 12p amplicon, is a potential germ cell tumour-specific oncogene.

A genetic hallmark of malignant germ cell tumours (GCTs) is isochromosome 12p, but oncogenes located in 12p that are specifically expressed in GCT have not yet been identified. SIN3-HDAC complex-associated factor (SINHCAF) is a subunit of the Sin3/histone deacetylase (HDAC) complex, and it defines a Sin3a-Hdac complex variant that is required for the self-renewal of mouse embryonic stem cells. This study demonstrated that SINHCAF is expressed in a vast majority of malignant GCTs and is rarely expressed in somatic malignancy.

Tumor-matrix interaction induces phenotypic switching in liver cancer cells.

Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix.

The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is one of the major increasing lethal malignancies of the gynecological tract, mostly due to delayed diagnosis and chemoresistance, as well as its very heterogeneous genetic makeup. Application of high-throughput molecular technologies, gene expression microarrays, and powerful preclinical models has provided a deeper understanding of the molecular characteristics of EOC. Therefore, molecular markers have become a potent tool in EOC management, including prediction of aggressiveness, prognosis, and recurrence, and identification of novel therapeutic targets.

Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of 9%. Major obstacles to successful treatment of pancreatic cancer are the immunosuppressive tumor microenvironment (TME) and antigenic complexity or heterogeneity. Programmed death-ligand 1 (PD-L1) is expressed on PDAC and immunosuppressed cells within the TME, providing suitable immunotherapy targets.

Correlation of molecular and morphological features of appendiceal epithelial neoplasms.

Aims: The aims of this study were to identify the genetic features of appendiceal epithelial neoplasms and correlate the genetic features with morphology.

Methods And Results: We analysed the genetic features of a series of 47 appendiceal epithelial neoplasms of various morphologies by using targeted next-generation sequencing of 11 genes commonly mutated in gastrointestinal neoplasms. Seven of nine serrated polyps harboured BRAF mutations, which are rare in other types of appendiceal tumours.

Increased Trimethylation of histone H3K36 associates with biliary differentiation and predicts poor prognosis in resectable hepatocellular carcinoma.

Introduction: Trimethylation of histone H3K36 (H3K36me3), an epigenetic marker of transcription-associated histone modification and stem cell regulation, is expressed in a variety of human cancers. This study elucidated the prognostic significance of H3K36me3 in patients with resectable hepatocellular carcinoma (HCC).

Methods: Expression of H3K36me3 was retrospectively evaluated through immunohistochemistry in 152 surgically resected primary HCCs.

Robotic major hepatectomy: Is there a learning curve?

Background: Robotic hepatectomy has been suggested as a safe and effective management of liver disease. However, no large case series have documented the learning curve for robotic major hepatectomy.

Method: We conducted a retrospective study for robotic major hepatectomy performed by the same operative team between January 2012 and October 2015 and evaluated the learning curve for operation time using the cumulative sum method, presented as cumulative sum.

RNF43 mutation frequently occurs with GNAS mutation and mucin hypersecretion in intraductal papillary neoplasms of the bile duct.

Aims: RNF43 is a tumour suppressor gene that suppresses the Wnt-β-catenin signalling pathway. We investigated the role of RNF43 in intraductal papillary neoplasm of the bile duct (IPNB).

Methods And Results: We conducted mutation analysis of RNF43 in 50 IPNBs, and identified six (12%) RNF43 mutations.

Paradoxical overexpression of MBNL2 in hepatocellular carcinoma inhibits tumor growth and invasion.

Pre-mRNA alternative splicing is an essential step in the process of gene expression. It provides cells with the opportunity to create various protein isoforms. Disruptions of alternative splicing are associated with various diseases, including cancer.

Tumor size is a major determinant of prognosis of resected stage I hepatocellular carcinoma.

Purpose: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) includes all solitary tumors without vascular invasion as stage I, regardless of tumor size. The aim of this study is to determine the prognostic significance of tumor size in stage I HCC patients.

Methods: A total of 230 stage I primary HCCs were selected retrospectively.

Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis.

Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control.

Expression of hypoxic marker carbonic anhydrase IX predicts poor prognosis in resectable hepatocellular carcinoma.

Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in hepatocellular carcinomas (HCCs) remains largely unknown. We examined the expression of 277 unifocal, resectable, primary HCC tumors using immunohistochemistry.

Expression of bile duct transcription factor HNF1β predicts early tumor recurrence and is a stage-independent prognostic factor in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) frequently exhibits biliary differentiation, which is typically overlooked. Hepatocyte nuclear factor 1β (HNF1β), a bile duct-specific transcription factor expressed in bile ducts but not in the normal hepatocytes, is also expressed in HCC.

Materials And Methods: The expression of HNF1β and the biliary differentiation marker cytokeratin 19 (CK19) were retrospectively evaluated using immunohistochemistry in 159 surgically resected primary HCCs.

TERT promoter mutation in resectable hepatocellular carcinomas: a strong association with hepatitis C infection and absence of hepatitis B infection.

Introduction: Mutation in the core promoter of the telomerase reverse transcriptase (TERT) gene was determined to be a frequent event in malignant melanoma and other cancers. However, the role of TERT promoter mutation in hepatocellular carcinomas (HCCs) remains largely unknown.

Methods: Genomic DNA samples from the tumor tissue of 195 HCCs were analyzed for TERT promoter mutation at 2 hotspots (-124 and -146 bp from the ATG start site, g.

Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features.

On the basis of morphological features, we subclassified 189 intrahepatic cholangiocarcinomas into two subtypes: bile duct and cholangiolar. The cholangiolar type is composed of cuboidal to low columnar tumor cells that contain scanty cytoplasm. The bile duct type is composed of tall columnar tumor cells arranged in a large glandular pattern.

Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs).

GNAS Is frequently mutated in a specific subgroup of intraductal papillary neoplasms of the bile duct.

Intraductal papillary neoplasms of the bile duct (IPN-Bs) share clinicopathologic features with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Approximately two thirds of IPMNs have activating point mutations of GNAS at codon 201. The role of GNAS mutation is unclear in IPN-B.

Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system.

Aims: Annexin A10 (ANXA10) is a calcium- and phospholipid-binding protein expressed normally in the gastric mucosa. In this study, we evaluated the potential use of ANXA10 as a diagnostic marker.

Methods And Results: We observed ANXA10 expression in the gastric mucosa, the Brunner gland of the duodenum and the urothelium, but absence of expression in other normal organs.

Pseudolymphoma of the liver: Report of a case and review of the literature.

We report a case of pseudolymphoma of the liver in a 49-year-old woman without an underlying disease except for liver hemangioma. A 20-mm nodule was incidentally found in segment 2 of the liver by abdominal ultrasonography during a regular follow-up of the hepatic hemangioma. After a series of radiological examinations, a left lateral sectionectomy was performed because malignant hepatic tumor could not be excluded.

Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis.

Collagen triple helix repeat containing-1 (CTHRC1) is a secreted glycoprotein that activates the planar cell polarity pathway of Wnt signaling. Using microarray analysis, we found that the CTHRC1 gene is overexpressed in hepatocellular carcinoma (HCC). The level of CTHRC1 mRNA was measured in 201 surgically resected HCCs using real time reverse transcription-polymerase chain reaction.

S100P expression is a novel prognostic factor in hepatocellular carcinoma and predicts survival in patients with high tumor stage or early recurrent tumors.

The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry.

p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression.

The p15(PAF)/KIAA0101 protein is a proliferating cell nuclear antigen (PCNA)-associated protein overexpressed in multiple types of cancer. Attenuation of p15(PAF) expression leads to modifications in the DNA repair process, rendering cells more sensitive to ultraviolet-induced cell death. In this study, we identified that p15(PAF) expression peaks during the S phase of the cell cycle.

Expression of insulin-like growth factor II mRNA-binding protein 3 predicts early recurrence and poor prognosis in intrahepatic cholangiocarcinoma.

Introduction: Insulin-like growth factor-II mRNA-binding protein 3 (IMP3), a newly identified oncofetal RNA-binding protein, plays a pivotal role in the regulation of cell growth and migration during early stages of embryogenesis, and is found to be expressed in various human cancers. In this study, we elucidated the clinicopathological significance of IMP3 expression in intrahepatic cholangiocarcinoma (ICC).

Methods: From March 1995 to December 2003, 61 surgically resected, unifocal primary ICCs were studied.

The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing.

Lin-41 is a stem cell-specific E3 ligase and a known target of the tumour suppressor microRNA (miRNA) let-7. Lin-41 was recently reported to mediate ubiquitylation and degradation of the miRNA pathway protein Ago2. We demonstrate that Lin-41 is over-expressed in hepatocellular carcinoma (HCC).

S100P immunostaining identifies a subset of peripheral-type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas.

Aims: S100P is a calcium-binding protein that is frequently expressed in pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study was to investigate the pathological significance of the expression of S100P in peripheral intrahepatic cholangiocarcinoma (ICC).

Methods And Results: Immunohistochemical staining was used to investigate S100P expression in 112 cases of peripheral ICC.