Aberrant cytoplasmic p53 expression and its correlation with TP53 mutation status and functional implications in stage II and III colorectal cancer.

Introduction: TP53 mutation is frequently observed in colorectal cancer (CRC) and is often linked to associated with immunohistochemical p53 expression patterns. Recent studies have identified cytoplasmic p53 expression in CRC, but its correlation with TP53 mutation domains and functional properties remains unclear.

Methods: We evaluated nuclear and cytoplasmic p53 staining patterns in 429 stage II and III CRC samples.

Multiplexed imaging-driven single-cell analysis of abdominal aortic aneurysm according to C-reactive protein deposition.

Abdominal aortic aneurysm (AAA) is an age-related, life-threatening condition characterized by the expansion of the abdominal aorta. Serum C-reactive protein (CRP) levels are a prognostic marker for AAA, and CRP accelerates tissue injury when deposited in damaged cell membranes in its monomeric form (mCRP). We previously showed that mCRP deposits in eroded atherosclerotic regions are associated with increases in inflammatory cell infiltration and aortic diameter.

The oncogenic role of hypomethylated ZNF793 in gastric carcinoma: a focus on cell survival and stemness.

Background: Although genome-wide promoter CpG island hypermethylation of Epstein-Barr virus-associated gastric carcinoma (EBV GC) is well known, ZNF793 is rarely methylated in EBV GC but is frequently methylated in other molecular subtypes of GC, including microsatellite instability-high GC. Based on the hypothesis that ZNF793 may be important for cell survival and stemness in EBV GC, the oncogenic role of ZNF793 was investigated.

Methods: ZNF793 expression was knocked out and then restored in EBV and non-EBV GC cell lines, and its effects on cell proliferation, cell migration, cell invasion, tumor sphere formation, and xenograft tumor formation were assessed.

Immunogenomic characteristics and prognostic implications of terminally exhausted CD8 T cells in colorectal cancers.

Introduction: T-cell exhaustion is a major mechanism of immune evasion. Recently, the therapeutic and prognostic implications of progenitor exhausted T cells (Tpex) and terminally exhausted T cells (Ttex) have been explored in various cancer types. This study explored the immunogenomic characteristics and prognostic implications of Tpex and Ttex in colorectal cancers (CRCs).

Value of the combination of intraepithelial tumor-infiltrating lymphocyte density and the heterogeneity of density as a prognostic marker in stage III colorectal cancers.

Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively.

CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights from spatial whole transcriptomic analysis.

Background: We investigated the effects of C-reactive protein (CRP) deposition on the vessel walls in abdominal aortic aneurysm (AAA) by analyzing spatially resolved changes in gene expression. Our aim was to elucidate the pathways that contribute to disease progression.

Methods: AAA specimens from surgically resected formalin-fixed paraffin-embedded tissues were categorized into the AAA-high CRP [serum CRP ≥ 0.

ALK Inhibition in a Patient with Inflammatory Myofibroblastic Tumor Harboring CARS1-ALK Fusion.

Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion.

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.

Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.

Deep learning-based histological predictions of chromosomal instability in colorectal cancer.

Colorectal cancer (CRC) is a lethal malignancy and a leading cause of cancer-related mortality worldwide. Chromosomal instability (CIN) is a key driver of genomic instability in CRC and is characterized by aneuploidy and somatic copy-number alterations. This study aimed to predict CIN in CRC using histological data from whole slide images (WSIs).

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.

Mitochondrial DNA mosaicism in normal human somatic cells.

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%.

Clinicopathological and molecular features of genome-stable colorectal cancers.

Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined.

Transformation of t(14;18)-negative follicular lymphoma to plasmablastic lymphoma: a case report with analysis of genetic evolution.

Background: Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21) involving the IGH and BCL2 genes. However, 10-15% of FLs lack the BCL2 rearrangement. These BCL2-rearrangement-negative FLs are clinically, pathologically, and genetically heterogeneous.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents..

Concomitant expression patterns of CDX2 and SATB2 as prognostic factors in stage III colorectal cancers.

CDX2 and SATB2 are often used as biomarkers for identification of colorectal origin in primary or metastatic adenocarcinomas. Loss of CDX2 or SATB2 expression has been associated with poor prognosis in patients with colorectal cancer (CRC). However, little is known regarding clinicopathological features, including prognosis, of CRCs with concomitant loss of CDX2 and SATB2.

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.

Backgruound: Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.

Methods: We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea.

Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists.

Background: The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education.

Methods: The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education.

Spatial and clonality-resolved 3D cancer genome alterations reveal enhancer-hijacking as a potential prognostic marker for colorectal cancer.

The regulatory effect of non-coding large-scale structural variations (SVs) on proto-oncogene activation remains unclear. This study investigated SV-mediated gene dysregulation by profiling 3D cancer genome maps from 40 patients with colorectal cancer (CRC). We developed a machine learning-based method for spatial characterization of the altered 3D cancer genome.

In-depth proteomic signature of parathyroid carcinoma.

Objective: Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC.

Design: We conducted a retrospective cohort study.

Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations.

Background: Germline mutations of breast cancer susceptibility gene BRCA1 and BRCA2 (gBRCA1/2) are associated with elevated risk of breast cancer in young women in Asia. BRCA1 and BRCA2 proteins contribute to genomic stability through homologous recombination (HR)-mediated double-strand DNA break repair in cooperation with other HR-related proteins. In this study, we analyzed the targeted sequencing data of Korean breast cancer patients with gBRCA1/2 mutations to investigate the alterations in HR-related genes and their clinical implications.

Development of quality assurance program for digital pathology by the Korean Society of Pathologists.

Background: Digital pathology (DP) using whole slide imaging is a recently emerging game changer technology that can fundamentally change the way of working in pathology. The Digital Pathology Study Group (DPSG) of the Korean Society of Pathologists (KSP) published a consensus report on the recommendations for pathologic practice using DP. Accordingly, the need for the development and implementation of a quality assurance program (QAP) for DP has been raised.

Composite scoring system and optimal tumor budding cut-off number for estimating lymph node metastasis in submucosal colorectal cancer.

Background: Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC.

Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas.

Although the density of tumor-infiltrating lymphocytes (TILs) is known to be linked to prognosis in various cancers, the prognostic impact and immunologic significance of the spatial heterogeneity of TILs have been rarely investigated. In this study, CD3+ and CD8+ TILs were quantified in independent cohorts (discovery, n = 73; and external validation, n = 93) of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) utilizing whole-slide image analysis of CD3/CD8 immunohistochemistry. The Shannon and Simpson indices, which measure intratumoral patch-to-patch evenness of TIL densities, were used to quantitatively assess the spatial heterogeneity of TILs in each case.