Epstein-Barr Virus-associated gastric cancer: a histopathologic study with comprehensive molecular profiling.

A subset of gastric cancers (GCs) is linked to Epstein-Barr virus (EBV) infection. This study aims to characterize the histopathological and molecular features of EBV-associated GCs (EBVaGCs), focusing on predictive biomarkers and genomic and transcriptomic analysis. A total of 35 primary EBVaGCs were considered.

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression.

To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection.

Fatty Pancreas Disease: An Integrated Study on Frozen Tissues Shows Distinct Compartments of Interlobular/Intralobular, Intra-Acinar, and Intra-Islet Fat Deposition.

Obesity-related diseases and perturbations of fat metabolism represent some of the most common health challenges. In this complex scenario, recent evidence has suggested the emergence of a condition related to fat accumulation in the pancreas, which is generally referred to as fatty pancreas disease. This study aimed to clarify the different compartments of intrapancreatic fat deposition.

Claudin-18.2 immunohistochemical evaluation in pancreatic cancer specimens: review and recommendations for routine testing and scoring.

The evaluation of claudin-18 (CLDN18) by immunohistochemistry (IHC) has already entered routine diagnostic activity as a predictive biomarker for patients with gastric and gastroesophageal junction adenocarcinomas. Of note, the CLDN18 gene encodes for 2 isoforms, claudin-18.1 (CLDN18.

Composite gangliocytoma/neuroma and neuroendocrine tumour: a contemporary analysis of 71 cases shows risk factors for metastasis.

Aims: To describe the clinicopathological features of composite gangliocytoma/neuroma and neuroendocrine tumour (CoGNET) and possible risk factors for nodal metastasis.

Methods And Results: We compiled a cohort of 71 cases from 19 institutions. Mean patient age was 58 years.

Recurrent BEND2 Fusion Genes Identified by Whole Transcriptome Sequencing of Non-Functional Pancreatic Neuroendocrine Tumors Correlate with Poor Patient Prognosis.

Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogeneous clinical behavior, and a growing number of NF-PanNETs have been discovered incidentally. While chromatin remodeling and telomere maintenance gene alterations, such as ATRX and DAXX mutations, are well-established in the metastatic progression of PanNETs, many tumors lack known driver mutations. To identify additional prognostic biomarkers and alternative oncogenic mechanisms in primary non-functional pancreatic neuroendocrine tumors (NF-PanNETs), we employed whole transcriptome sequencing (WTS) on 73 non-syndromic NF-PanNETs with extended clinical follow-up (>4 years).

Urinary Tumor DNA-based Liquid Biopsy in Bladder Cancer Management: A Systematic Review.

Background And Objective: Urinary tumor DNA (utDNA) has emerged as a promising biomarker in the care, diagnosis, early detection, recurrence monitoring, and prognosis of bladder cancer (BCa). Its noninvasive nature, ease of access, and cost effectiveness make it an attractive option for both patients and health care providers. This review describes the current state of utDNA as a marker of BCa.

The importance of tumor microenvironment modulations in the progression of pancreatic intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have attracted substantial attention since they represent the most prevalent macroscopic precursor of pancreatic cancer. Most lesions show an epithelium with low-grade dysplasia and will remain indolent and unknown to the patient. Notably, a subgroup of IPMNs will progress to invasive cancer through a stepwise process characterized by the accumulation of specific genomic alterations and concomitant modifications of the tumor microenvironment (TME).

The Brescia International Multidisciplinary Consensus Guidelines on the Optimal Pathology Assessment and Multidisciplinary Pathways of Non-Pancreatic Neoplasms in and Around the Ampulla of Vater (PERIPAN).

Importance: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

Objective: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

Design: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology (SIGN), including the Delphi methodology and the AGREEII tool for quality assessment and external validation.

Biliary adenofibroma and cholangiocarcinoma: neighbors or relatives? A systematic and critical review.

Biliary adenofibroma (BAF) is currently classified as a benign intrahepatic biliary tumor. However, a growing body of literature has documented BAFs with invasive components or associated cholangiocarcinoma. To better characterize this challenging entity, we performed a systematic review of BAF.

Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy.

The introduction of immunotherapy has dramatically changed the paradigm of solid tumor treatment with the creation of novel therapeutic opportunities even for tumors that currently lack valid therapeutic options in the advanced or metastatic setting. Initially, the role of deficient mismatch repair status (dMMR)/microsatellite instability (MSI) as a predictive biomarker was confined to colorectal cancer. In 2017, MSI/dMMR became the first true agnostic biomarker to stratify patient response to immune checkpoint inhibitors.

ARID1A mutational status in non-small cell lung cancer: from molecular pathology to clinical implications with a focus on the relationships with EGFR.

Lung cancer is the most frequently diagnosed malignancy worldwide and remains the leading cause of cancer-related mortality. Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, with epidermal growth factor receptor (EGFR) gene mutations being among the most frequently reported. ARID1A (AT-Rich Interactive Domain 1A), a key component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, has emerged as a tumor suppressor in multiple cancers and is mutated in approximately 8 % of lung cancers, primarily as a loss-of-function (LOF) alteration, which allows the gene to be considered a potential molecular marker, predictive of poor NSCLC prognosis.

Mucinous cystic neoplasms and simple mucinous cysts are two distinct precursors of pancreatic cancer: clinicopathological, genomic, and transcriptomic characterization.

Mucinous cystic neoplasms (MCNs) of the pancreas are macroscopic precursors of pancreatic cancer. A similar cystic lesion but lacking the ovarian-type subepithelial stroma has been recently defined as a simple mucinous cyst (SMC); however, its nature remains unclear. This study aims to define the clinicopathological and molecular profiles of a cohort of MCNs and SMCs of the pancreas and their associated invasive carcinoma.

Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases.

Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness.

Positive Lymph Nodes Independently Affect Long-Term Survival After Pancreaticoduodenectomy for Non-Ampullary Duodenal Adenocarcinoma: A Single-Center, Retrospective Analysis.

: The main treatment for non-ampullary duodenal adenocarcinoma (NDA) is pancreatoduodenectomy (PD) with lymphadenectomy (LN). Several studies have proposed a minimum number of examined lymph nodes (MNELN) to ensure proper staging. This study investigated the impact of nodal parameters-including the pattern of nodal spread-on oncologic outcomes following PD for NDA.

Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination.

Background: Temporal and spatial molecular heterogeneity contributes to resistance to targeted and immune therapies in gastric and esophagogastric junction carcinoma (G/EGJ). This study evaluates differences in biomarker expression between primary G/EGJ and paired peritoneal metastases (PM).

Methods: We analyzed 74 cases of primary G/EGJ and paired PM using immunohistochemistry for HER2, PD-L1, Claudin18 (CLDN18), DNA mismatch repair (MMR) proteins, p53, E-cadherin, and in situ hybridization for EBER.

Management of patients with small pancreatic neuroendocrine tumors from a biomarker and surgical perspective.

Pancreatic neuroendocrine tumors (PanNETs) have an age-adjusted incidence of 1.5 per 100,000 people, with a notable rise in the incidence of small (≤2 cm) non-functional PanNETs (NF-PanNETs) in recent decades. While surgery is traditionally the preferred treatment for localized NF-PanNETs, active surveillance is now an accepted management strategy for tumors smaller than 2 cm due to their relatively benign behavior.

MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC.

Intratumour heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance. Oncogene dosage variation contributes to cell-state transitions and phenotypic heterogeneity, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood.

Liquid biopsy in gastric cancer: A snapshot of the current state of the art.

Circulating tumor DNA (ctDNA) is nowadays considered a robust source to search for druggable tumoral genetic alterations, and in some specific settings liquid biopsy (LB) is already part of the diagnostics scenario and it has successfully implemented in the everyday practice. Three strengths make LB an extraordinary tool: i) to represent the complex molecular mosaicism that characterizes spatially heterogeneous malignancies; ii) to monitor in real-time the tumoral molecular landscape (i.e.

Clinical Relevance of ATRX/DAXX Gene Mutations and ALT in Functioning Pancreatic Neuroendocrine Tumors.

Functioning pancreatic neuroendocrine tumors (PanNETs) represent a subset of PanNETs that cause symptoms due to hormonal activity. Insulinoma is the most common functioning PanNET type. Mutations in the alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes result in genomic instability.

Potentialities and critical issues of liquid biopsy in clinical practice: An umbrella review.

Background: Liquid biopsy (LB) is a laboratory test performed on a fluid sample aiming at analyzing molecular data derived from circulating cells and related entities, or from nucleic acids. This umbrella review aims to map and evaluate the evidence supporting the use of LB in medicine across different medical specialities and conditions.

Methods: We searched three repositories from database inception up to October 1, 2023 and we included meta-analyses of observational studies reporting data on the use of LB, compared to gold standard, and its accuracy (area under the curve, AUC).

MLH1 gene promoter methylation status partially overlaps with CpG methylator phenotype (CIMP) in colorectal adenocarcinoma.

Background: RAS/BRAF mutations, mismatch DNA repair complex deficiency (MMRd)/microsatellite instability (MSI), and CpG methylator phenotype (CIMP) are key molecular actors in colorectal carcinogenesis. To date, conflicting evidence about the correlations between these molecular features has been reported.

Materials And Methods: A retrospectively selected cohort of 123 CRCs was divided into 3 groups based on the molecular characteristics: MMR proficient (MMRp)/BRAF p.