Fluorescence in-situ hybridization

PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4 -specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108)...

We developed T1AL·1PS and T1AS·1PL Robertsonian translocations by breakage-fusion mechanism based on wheat-A. cristatum 1P(1A) substitution line with smaller leaf area, shorter plant height, and other excellent agronomic traits Agropyron cristatum, a wild relative of wheat, is a valuable germplasm resource for improving wheat genetic diversity and yield. Our previous study confirmed that the A. cristatum chromosome 1P carries alien genes that reduce plant height and leaf size in wheat. Here, we developed T1AL·1PS and T1AS·1PL Robertsonian translocations (RobTs) by breakage-fusion mechanism based on wheat-A...

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA)...

Thyroid hormones (TH) play critical roles during nervous system development and patients carrying coding variants of MCT8 (monocarboxylate transporter 8) or THRA (thyroid hormone receptor alpha) present a spectrum of neurological phenotypes resulting from perturbed local TH action during early brain development. Recently, human cerebral organoids (hCOs) emerged as powerful in vitro tools for disease modelling recapitulating key aspects of early human cortex development. To begin exploring prospects of this model for thyroid research, we performed a detailed characterization of the spatiotemporal expression of MCT8 and THRA in developing hCOs...

The fusion of neurotrophic tyrosine receptor kinase (NTRK) is a novel target for cancer therapy and offers hope for patients with gastric cancer (GC). However, there are few studies on the prevalence and detection methods of NTRK fusions in GC. In this study, we used immunohistochemistry (IHC) as a screening method to select cases for molecular testing and evaluated the effectiveness of IHC, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). We retrospectively collected 1970 patients with GC...

AIMS: Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others...

BACKGROUND: There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real-time polymerase chain reaction (RT-qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67). METHODS: We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer...

As genomic medicine advances, opportunities for molecular pathology diagnosis by pathologists to be used as companion diagnostics is increasing. Pathological specimens must be useful not only for pathological diagnosis, but also for genetic testing panel and molecular pathology diagnosis. Companion diagnostics performed by pathologists uses immunohistochemical staining and fluorescence in situ hybridization to determine patient eligibility for molecular target drugs and immune checkpoint inhibitors. By accurately observing a wide variety of diagnostic criteria and performing with high precision, pathological diagnosis will become closer to therapeutic pathology...

Homozygous deletion of the chromosomal region 9p21.3 is common in urothelial carcinoma (UC) and leads to loss of several genes, including CDKN2A and MTAP, resulting in loss of MTAP protein expression. Here, we aimed at exploring the diagnostic potential of MTAP immunohistochemistry (IHC) as a surrogate marker for homozygous 9p21.3 deletion (9p21 HD) in UC. MTAP status was determined by IHC on 27 UC tissue specimens with known 9p21.3 status as defined by fluorescence in situ hybridization (FISH) in matched cytological specimens, by IHC and FISH on a tissue microarray (TMA) containing 359 UC at different stages, and by IHC on 729 consecutive UC from routine practice...

Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. To investigate expression and function of Tmc1 and Tmc2 in vestibular organs, we used quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization - hairpin chain reaction (FISH-HCR), immunostaining, FM1-43 uptake and we measured vestibular evoked potentials (VsEPs) and vestibular ocular reflexes (VORs). We found that Tmc1 and Tmc2 showed dynamic developmental changes, differences in regional expression patterns, and overall expression levels which differed between the utricle and saccule...

BACKGROUND: Compared to other ethnicities, Hispanics/Latinos (H/L) have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetic subtypes, and worse outcomes, even after correcting for socioeconomic factors. We previously demonstrated increased incidence of the high-risk genetic drivers IKZF1 deletion and IGH::CRLF2 rearrangement in H/L compared to non-H/L children with B-ALL. Here in an expanded pediatric cohort, we sought to identify novel genetic drivers and secondary genetic alterations in B-ALL associated with H/L ethnicity...

Dysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues...

Rhabdomyosarcoma with TFCP2-related fusions (TFCP2-RMS) is a rare entity that commonly affects young adults with a predilection for skeletal involvement. We herein report a 40-year-old female patient with TFCP2-RMS who was misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma of the mandible by referring institutions. Histologically, the tumor showed dominant spindle cells and focal epithelioid cells with marked immature woven bone formation. Immunophenotypically, in addition to the characteristic expression of myogenic markers, ALK, and cytokeratins, tumor cells also unusually expressed osteogenic markers, such as MDM2 and SATB2...

Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy...

Human epidermal growth factor receptor 2 (HER2) expression has become increasingly helpful in predicting responses to anti-HER2 agents in gynecological cancers. This study retrospectively analyzed HER2 expression in 48 primary ovarian endometrioid carcinomas. HER2 immunohistochemistry was performed using the Ventana platform (Clone 4B5 monoclonal predilute) following the manufacturer's protocol. HER2 expression was equivocal (score 2+) by image analysis in 2 cases (4.17%) based on the breast cancer criteria...

Primary malignant cardiac tumors rarely occur, and cardiac synovial sarcoma (SS) is especially rare among such tumors. Herein, we present the case of a 35-year-old female with primary cardiac SS treated with surgery, chemotherapy, and radiotherapy. She presented with chest symptoms and underwent imaging examinations. A cardiac tumor was suspected, and an open biopsy was performed. The pathological findings suggested cardiac SS. Next, we performed a resection, and the tumors persisted at a macroscopic level...

Runt-related transcription factor 1 (RUNX1)::RUNX1 partner transcriptional co-repressor 1 (RUNX1T1) acute myeloid leukemia (AML) is a subtype of acute leukemia primarily classified as French American British M2. RUNX1::RUNX1T1 transcript is formed by a reciprocal translocation between chromosomes 8q22 and 21q22. However, we encountered a case of AML that showed molecular positivity for RUNX1::RUNX1T1 fusion transcript but exhibited cytogenetically atypical translocation t(6;8). Fluorescence in situ hybridization (FISH) analysis, in combination with G-banding, clarified the three-way translocation t(6;21;8)(p25;q22;q22), which was partially cryptic...

Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production...

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited...

CONTEXT.—: Most patients with non-small cell lung cancers (NSCLC) are diagnosed at advanced stages. The 5-year survival rate of patients with advanced lung cancer is less than 20%, which makes lung cancer the leading cause of cancer-related deaths worldwide. OBJECTIVE.—: To identify indicators that can predict the prognosis of lung cancer patients. DESIGN.—: To determine the correlation between circulating tumor cells (CTCs), circulating tumor-derived endothelial cells (CTECs), and their subtypes and the prognosis of patients with NSCLC, 80 patients with lung cancer were recruited and 48 patients who met the enrollment criteria were selected in this study...