Grade Group accuracy is improved by extensive prostate biopsy sampling, but unrelated to prostatectomy specimen sampling or use of immunohistochemistry.

Assessing the accurate Grade Group of a prostate needle biopsy specimen is essential for choosing the adequate therapeutic modality for prostate cancer patients. However, it is well-known that biopsy Grade Group tends to up- or downgrade significantly at radical prostatectomy. We aimed to investigate the correlation between accuracy and biopsy core number, performed immunohistochemical staining (IHC) or prostatectomy specimen sampling, with the latest also being correlated with higher detection rates of adverse pathological features, e.

Hydrogen sulfide as an anti-calcification stratagem in human aortic valve: Altered biogenesis and mitochondrial metabolism of HS lead to HS deficiency in calcific aortic valve disease.

Hydrogen sulfide (HS) was previously revealed to inhibit osteoblastic differentiation of valvular interstitial cells (VICs), a pathological feature in calcific aortic valve disease (CAVD). This study aimed to explore the metabolic control of HS levels in human aortic valves. Lower levels of bioavailable HS and higher levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected in aortic valves of CAVD patients compared to healthy individuals, accompanied by higher expression of cystathionine γ-lyase (CSE) and same expression of cystathionine β-synthase (CBS).

Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy.

The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.

Carbonic Anhydrase IX (CAIX) Expressing Hypoxic Micro-environment Hampers CD8+ Immune Cell Infiltrate in Breast Carcinoma.

Background: Hypoxia and necrosis are common features of invasive cancer. The dynamic upregulation of carbonic anhydrase IX (CAIX), triggered by hypoxia-inducible factor 1 (HIF-1) is 1 of the mechanisms supporting cellular adaptation to hypoxia in solid tumors, including breast carcinoma. CAIX activity results in extracellular acidosis and in a profound reorganization of the tumor micro-environment, influencing biological behavior and prognosis.

Cutaneous metastases at the sites of pembrolizumab-induced bullous pemphigoid lesions in a patient with melanoma.

The authors report a case of bullous pemphigoid (BP) that occurred during pembrolizumab therapy in a 67-year-old male patient with advanced melanoma. Following regression of BP blisters, they reintroduced anti-PD-1 treatment. Due to the flare-up of BP, immunotherapy was discontinued again and corticosteroid was restarted.

Anastomosing Haemangioma: Report of Three Cases With Molecular and Immunohistochemical Studies and Comparison With Well-Differentiated Angiosarcoma.

Anastomosing haemangioma (AH) is a newly described distinct vascular neoplasm that histologically may confuse with well-differentiated angiosarcoma (AS) for those who are unfamiliar with this rare entity. We aimed to identify molecular genetic differences between AHs and ASs by carrying out immunohistochemistry (IHC), fluorescence hybridization (FISH), and next-generation sequencing (NGS). Immunohistochemically, all six cases showed positivity for cyclinD1 and pERK.

Ferryl Hemoglobin and Heme Induce A-Microglobulin in Hemorrhaged Atherosclerotic Lesions with Inhibitory Function against Hemoglobin and Lipid Oxidation.

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions.

Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression.

Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry.

Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using Ga-NODAGA-c(NGR) Peptide.

Introduction: The aminopeptidase N (APN/CD13) receptor plays an important role in the neoangiogenic process and metastatic tumor cell invasion. Clinical and preclinical studies reported that bestatin and actinonin are cytotoxic to APN/CD13-positive tumors and metastases due to their APN/CD13-specific inhibitor properties. Our previous studies have already shown that Ga-labeled NGR peptides bind specifically to APN/CD13 expressing tumor cells.

The Prognostic Relevance of Poly (ADP-Ribose) Polymerase Expression in Ovarian Cancer Tissue of Wild Type and BRCA-Mutation Carrier Patients.

(1) Background: The mechanism of platinum resistance in ovarian cancer is not fully clarified, but the properly functioning DNA repair mechanism can counteract the effect of conventional anticancer treatment. The objective of our study was to evaluate the expression of an important DNA repair enzyme, the Poly (ADP-Ribose) Polymerase (PARP) expression in epithelial ovarian cancer (EOC) tissues depending on BRCA status and to assess its relationship with platinum resistance. (2) Methods: Immunostaining to highlight PARP protein expression was performed using a rabbit polyclonal anti-PARP antibody.

Hydrogen sulfide inhibits aortic valve calcification in heart via regulating RUNX2 by NF-κB, a link between inflammation and mineralization.

Introduction: Hydrogen sulfide (HS) was revealed to inhibit aortic valve calcification and inflammation was implicated in the pathogenesis of calcific aortic valve disease (CAVD).

Objectives: We investigate whether HS inhibits mineralization via abolishing inflammation.

Methods And Results: Expression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased in patients with CAVD and in calcified aortic valve of ApoE-/- mice.

Carbonic Anhydrase Inhibitor Acetazolamide Enhances CHOP Treatment Response and Stimulates Effector T-Cell Infiltration in A20/BalbC Murine B-Cell Lymphoma.

The inhibition of cancer-related carbonic anhydrase (CA) activity is a promising way to intensify anti-tumor responses. In vitro data suggest improved efficacy of cytotoxic drugs in combination with CA-inhibitors in several cancer types. Despite accumulating data on CA-expression, experimental or clinical studies towards B-cell lymphoma therapy are missing.

The Prognostic Value of PARP Expression in High-Grade Epithelial Ovarian Cancer.

In an attempt to clarify the prognostic relevance of poly (ADP-ribose) polymerase (PARP) expression, we analysed the clinical data of 86 high-grade epithelial ovarian cancer (EOC) cases in which PARP immunohistochemistry results were available. Immunostaining to highlight PARP protein expression was performed using a Leica Bond MAX Immunostainer (Leica Microsystems, Wetzlar, Germany). We applied a rabbit polyclonal anti-PARP antibody (ab6079 330, Abcam, Cambridge, UK) for the specific reaction.

A novel splice site indel alteration in the EIF2AK3 gene is responsible for the first cases of Wolcott-Rallison syndrome in Hungary.

Background: Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene.

Methods: Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing.

High Genetic Diversity and No Evidence of Clonal Relation in Synchronous Thyroid Carcinomas Associated with Hashimoto's Thyroiditis: A Next-Generation Sequencing Analysis.

The close association between pre-existing Hashimoto's thyroiditis and thyroid cancer is well established. The simultaneous occurrence of multiple neoplastic foci within the same organ suggests a common genotoxic effect potentially contributing to carcinogenesis, the nature of which is still not clear. Next-generation sequencing (NGS) provides a potent tool to demonstrate and compare the mutational profile of the independent neoplastic foci.

First Glance of Molecular Profile of Atypical Cellular Angiofibroma/Cellular Angiofibroma with Sarcomatous Transformation by Next Generation Sequencing.

Cellular angiofibroma is a rare benign mesenchymal neoplasm most commonly occurring in the vulvovaginal region in women and the inguinoscrotal region in men with specific genetic deletion involved in the gene in chromosome 13q14 region. Atypical cellular angiofibroma and cellular angiofibroma with sarcomatous transformation are recently described variants showing worrisome morphological features and strong, diffuse p16 expression. Nevertheless, the molecular profile of these tumor entities is largely unknown.

Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity.

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway.

Quantitative Analysis of Carbonic Anhydrase IX Uncovers Hypoxia-Related Functional Differences in Classical Hodgkin Lymphoma Subtypes.

Upregulation of carbonic anhydrase IX (CAIX) was found to be associated with unfavorable prognosis and resistance to treatment in a broad spectrum of malignancies, recently also in classical Hodgkin's lymphoma (cHL). As demonstrated, variable CAIX expression in a significant number of cHL cases was associated with poor treatment response. The current study focused on the quantification CAIX immunopositivity and its relative expression compared to the total CD30+ neoplastic pool using digital image analysis.

Potential Role of H-Ferritin in Mitigating Valvular Mineralization.

Objective- Calcific aortic valve disease is a prominent finding in elderly and in patients with chronic kidney disease. We investigated the potential role of iron metabolism in the pathogenesis of calcific aortic valve disease. Approach and Results- Cultured valvular interstitial cells of stenotic aortic valve with calcification from patients undergoing valve replacement exhibited significant susceptibility to mineralization/osteoblastic transdifferentiation in response to phosphate.

Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma.

Aims: The present study evaluates the impact of hypoxia-related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL).

Methods And Results: Eighty-one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia-related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin-Reed-Sternberg (HRS) cells in 39 of 81 samples (48.

Programmed Death-ligand 1 (PD-L1) Expression in Thymic Epithelial Tumors.

Thymic epithelial tumors (TETs) are uncommon neoplasms of the mediastinum. The gold standard treatment is complete surgical resection which can be followed by radio/chemotherapy in selected cases. Targeted tyrosine kinase inhibition can be considered in only a limited number of aggressive or metastatic tumors as EGFR, BRAF, or c-kit mutations are rare.

Distinct Dynamics of Mitotic Transition in B-Cell Lymphoma and Reactive B-Cell Lymphoproliferations Determined by H3S10 Phosphohistone Immunolabeling.

Objectives: Clonal selection in the follicular germinal centers in lymphatic tissues is accompanied by an intense proliferation of polyclonal B cells in a precisely regulated fashion. In contrast, B-cell neoplasias proliferate autonomously due to endogenous stimuli. The cell kinetic activity is obvious at many levels including progressive chromatin modification and elevated mitotic rates.

Mitotic Index Determined by Phosphohistone H3 Immunohistochemistry for Precise Grading in Follicular Lymphoma.

The World Health Organization classification recommends follicular lymphoma (FL) grading (G1-3) by considering centroblast number, while also suggesting its influence on disease outcome. As centroblast counting and other proliferation markers have limitations, we looked for more specific measures of cellular activity in FL. Phosphorylated histone H3 (pHH3) was widely applied for the objective detection of mitotic activity in different tumors.

Mutant KRAS Status Is Associated with Increased KRAS Copy Number Imbalance: a Potential Mechanism of Molecular Heterogeneity.

Mutation rates determined by allele-specific PCR can be highly different in KRAS exon 2 mutant colorectal carcinoma (CRC) samples suggesting intratumoural heterogeneity. To address the effect of KRAS gene copy number on the relative mutant allele frequency the KRAS locus was individually quantified following FISH analysis in 36 cases. We observed, that mutant KRAS status was associated with an elevated KRAS locus number (2.