Tumor microenvironment-based classification for predicting gastric cancer prognosis.

Background: The tumor microenvironment (TME), consisting of tumor-associated stroma and tumor-infiltrating lymphocytes (TIL), is crucial for prognostic information in gastric cancer (GC). Despite its potential, routine clinical adoption remains limited.

Methods: In a study of 320 GC patients, virtual staining and image processing were applied to hematoxylin & eosin-stained slides.

Angiogenesis gene signatures in patient-derived tumor spheroids for genetic and tumor angiogenesis profiling.

: gastric cancers are highly vascular tumors, with elevated pro-angiogenic factors correlating with a poor prognosis. Despite advancements in precision medicine, there remains a critical need for platforms capable of identifying patient-specific therapeutic vulnerabilities. In this study, we present a 3D-printed patient-specific tumor angiogenesis chip that integrates genetic data to evaluate the molecular and functional characteristics of tumor angiogenesis in tumor spheroids derived from patients with gastric cancer.

Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach.

Background: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.

FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma.

Gastric and gastroesophageal junction cancer (G/GEJC) is a heterogeneous and complex disease characterized by histologic and molecular subtypes. Although a growing number of treatments have improved survival outcomes in the advanced setting, the greatest therapeutic benefits are observed among patient populations eligible for biomarker-directed therapies. Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) is an emerging biomarker under phase 3 clinical investigation for G/GEJC with the novel monoclonal antibody bemarituzumab.

Combined Biomarkers for Prediction of Immune Checkpoint Inhibitor Response in Patients With Triple-negative Breast Cancer.

Background/aim: Triple-negative breast cancer (TNBC) is an aggressive malignancy with few available targeted therapies. In this study, we examined the predictive power of several biomarkers, comprising the IMmunotherapy Against GastrIc Cancer (IMAGiC) model, PD-L1 combined positive score (CPS), intra-tumoral tumor-infiltrating lymphocytes (iTILs), and stromal TILs (sTILs), in an Asian population of patients with metastatic TNBC treated with immunotherapy.

Patients And Methods: Thirty-one metastatic TNBC patients receiving immunotherapy were analyzed.

Development and application of deep learning-based diagnostics for pathologic diagnosis of gastric endoscopic submucosal dissection specimens.

Background: Accurate diagnosis of ESD specimens is crucial for managing early gastric cancer. Identifying tumor areas in serially sectioned ESD specimens requires experience and is time-consuming. This study aimed to develop and evaluate a deep learning model for diagnosing ESD specimens.

Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.

Purpose: Adding pembrolizumab to first-line fluoropyrimidine (5-FU)/platinum chemotherapy plus trastuzumab improves outcomes in advanced HER2+ gastroesophageal adenocarcinomas, but the benefit is largely confined to dual HER2+ and PD-L1+ patients. To assess the contributions of components, we conducted a phase II trial evaluating 5-FU/platinum/trastuzumab and added pembrolizumab in cycle 2 in patients with metastatic HER2+ disease.

Patients And Methods: Treatment-naïve patients with advanced HER2+ gastroesophageal cancer underwent a baseline biopsy and received a single dose of 5-FU/platinum with trastuzumab followed by repeat biopsy.

Epidermal Growth Factor Receptor Aberrations Identified by Next-generation Sequencing in Patients with Metastatic Cancers.

Purpose: The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.

Materials And Methods: We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center.

PD-L1 as a Biomarker in Gastric Cancer Immunotherapy.

Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC.

Clinicopathologic and genomic characteristics of biliary tract carcinomas with TERT promoter mutations among East Asian population.

Telomerase reverse transcriptase gene promoter (TERT) mutations are biomarkers that predict survival and responses to immune checkpoint inhibitors in various malignancies. However, their prevalence and clinicopathologic characteristics in biliary tract carcinomas are largely unknown. We performed a comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 485 carcinomas, including intrahepatic (n = 220), perihilar (n = 54), distal biliary tract (n = 110), and gallbladder (n = 101) cancers, using next-generation sequencing.

Distinct genomic, transcriptomic, and immune profiles for tumor and non-tumor mucosal regions in early gastric cancer.

In early gastric cancer, local recurrence develops after endoscopic resection by field cancerization. Understanding the nature of cancer-prone environments is important to establish effective strategies to prevent recurrence. We hypothesized that the molecular/immune profiles in non-tumor (cancer-prone) tissue differ according to the relative distance from the gastric tumor.

Autoimmune Gastritis in Korean Patients with Gastric Tumors: Clinicopathologic Correlations and Diagnostic Histological Features.

Background/aims: Autoimmune gastritis (AIG) is a corpus-dominant atrophic gastritis in which patients are positive for antiparietal cell antibody (APCA) and/or anti-intrinsic factor antibody. The risk of developing gastric cancer in patients with AIG remains unclear, and reliable frequency data of AIG in patients with gastric cancer are lacking.

Methods: We included 624 Korean patients with gastric tumors (612 gastric cancers and 12 neuroendocrine tumors) who had APCA results and were available for AIG evaluation.

Association of ATM and ARID1A in gastric carcinoma.

Background: The ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear.

Clinicopathologic Features and Outcomes of Endoscopic Submucosal Dissection for Foveolar-Type Adenocarcinoma of the Stomach.

Purpose: Foveolar-type adenocarcinoma of the stomach is a rare variant of gastric cancer. The clinicopathological features and outcomes of endoscopic submucosal dissection (ESD) for gastric foveolar-type adenocarcinoma remain unclear.

Materials And Methods: This study included 1,161 patients who underwent ESD for single early gastric cancers (EGCs) (78 foveolar-type adenocarcinomas and 1,083 well-differentiated [WD] adenocarcinomas).

Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

Background: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging.

Methods: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations.

Prognostic Effect of Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated Gastric Carcinomas Measured by Digital Image Analysis.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent tumor-infiltrating lymphocytes (TILs) and has a favorable prognosis. Tertiary lymphoid structures (TLS), characterized by ectopic aggregated lymphocytes with high-endothelial venules (HEV), are associated with favorable outcomes in various solid tumors. We hypothesized that EBVaGC, characterized by intense TILs, may be closely associated with TLS or HEV.

Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

Background And Aims: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC.

Methods: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed.

Establishment of a patient-specific avatar organoid model derived from EUS-guided fine-needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma (with video).

Background And Aims: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC.

Patient-derived tumor spheroid-induced angiogenesis preclinical platform for exploring therapeutic vulnerabilities in cancer.

This study addresses the demand for research models that can support patient-treatment decisions and clarify the complexities of a tumor microenvironment by developing an advanced non-animal preclinical cancer model. Based on patient-derived tumor spheroids (PDTS), the proposed model reconstructs the tumor microenvironment with emphasis on tumor spheroid-driven angiogenesis. The resulting microfluidic chip system mirrors angiogenic responses elicited by PDTS, recapitulating patient-specific tumor conditions and providing robust, easily quantifiable outcomes.

Comparative analysis of ARID1A mutations with mRNA levels and protein expression in gastric carcinoma.

The ARID1A gene is pivotal in chromatin remodeling and genomic integrity and is frequently mutated in various cancer types. ARID1A mutation is the second most frequently mutated tumor suppressor gene and has been suggested as a predictor of immunotherapeutic responsiveness in gastric carcinoma (GC). Despite its significance, the relationship among ARID1A somatic mutations, RNA expression levels, and protein expression remains unclear, particularly in GC.