Mastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, ...including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that are relevant to the pathology. Epigenetic alterations are responsible for regulating the expression of genes that do not modify the DNA sequence. In general, it is accepted that DNA methylation inhibits the binding of transcription factors, thereby down-regulating gene expression. However, so far, little is known about the epigenetic factors leading to the clinical onset of mastocytosis. Therefore, it is essential to identify possible epigenetic predictors, indicators of disease progression, and their link to the clinical picture to establish appropriate management and a therapeutic strategy. The aim of this study was to analyze genome-wide methylation profiles to identify differentially methylated regions (DMRs) in patients with mastocytosis compared to healthy individuals, as well as the genes located in those regulatory regions. Genome-wide DNA methylation profiling was performed in peripheral blood collected from 80 adult patients with indolent systemic mastocytosis (ISM), the most prevalent subvariant of mastocytosis, and 40 healthy adult volunteers. A total of 117 DNA samples met the criteria for the bisulfide conversion step and microarray analysis. Genome-wide DNA methylation analysis was performed using a MethylationEPIC BeadChip kit. Further analysis was focused on the genomic regions rather than individual CpG sites. Co-methylated regions (CMRs) were assigned via the CoMeBack method. To identify DMRs between the groups, a linear regression model with age as the covariate on CMRs was performed using Limma. Using the available data for cases only, an association analysis was performed between methylation status and tryptase levels, as well as the context of allergy, and anaphylaxis. KEGG pathway mapping was used to identify genes differentially expressed in anaphylaxis. Based on the DNA methylation results, the expression of 18 genes was then analyzed via real-time PCR in 20 patients with mastocytosis and 20 healthy adults. A comparison of the genome-wide DNA methylation profile between the mastocytosis patients and healthy controls revealed significant differences in the methylation levels of 85 selected CMRs. Among those, the most intriguing CMRs are 31 genes located within the regulatory regions. In addition, among the 10 CMRs located in the promoter regions, 4 and 6 regions were found to be either hypo- or hypermethylated, respectively. Importantly, three oncogenes—FOXQ1, TWIST1, and ERG—were identified as differentially methylated in mastocytosis patients, for the first time. Functional annotation revealed the most important biological processes in which the differentially methylated genes were involved as transcription, multicellular development, and signal transduction. The biological process related to histone H2A monoubiquitination (GO:0035518) was found to be enriched in association with higher tryptase levels, which may be associated with more aberrant mast cells and, therefore, more atypical mast cell disease. The signal in the BAIAP2 gene was detected in the context of anaphylaxis, but no significant differential methylation was found in the context of allergy. Furthermore, increased expression of genes encoding integral membrane components (GRM2 and KRTCAP3) was found in mastocytosis patients. This study confirms that patients with mastocytosis differ significantly in terms of methylation levels in selected CMRs of genes involved in specific molecular processes. The results of gene expression profiling indicate the increased expression of genes belonging to the integral component of the membrane in mastocytosis patients (GRM2 and KRTCAP3). Further work is warranted, especially in relation to the disease subvariants, to identify links between the methylation status and the symptoms and novel therapeutic targets.
The study presents a full analysis of the Y-chromosome variability of the modern male Polish population. It is the first study of the Polish population to be conducted with such a large set of data ...(2,705 individuals), which includes genetic information from inhabitants of all voivodeships, i.e., the first administrative level, in the country and the vast majority of its counties, i.e., the second level. In addition, the available data were divided into clusters corresponding to more natural geographic regions. Genetic analysis included the estimation of
F
ST
distances, the visualization with the use of multidimensional scaling plots and analysis of molecular variance. Y-chromosome binary haplogroups were classified and visualized with the use of interpolation maps. Results showed that the level of differentiation within Polish population is quite low, but some differences were indicated. It was confirmed that the Polish population is characterized by a high degree of homogeneity, with only slight genetic differences being observed at the regional level. The use of regional clustering as an alternative to counties and voivodeships provided a more detailed view of the genetic structure of the population. Those regional differences identified in the present study highlighted the need for additional division of the population by cultural and ethnic criteria in such studies rather than just by geographical or administrative regionalization.
Endometriosis is a quite common pathology, however, intestinal endometriosis is a rare condition, which typically occurs with chronic symptoms. Its acute presentation is very infrequent. We herein ...report four cases of intestinal endometriosis, in which the clinical debut occurred acutely: two as an acute small bowel obstruction and two as a small bowel perforation. None of the cases had a preoperative diagnosis of endometriosis. The interest of these cases lies in this exceptional form of presentation, such as a surgical acute abdomen. Therefore, intestinal endometriosis should be taken into account in the differential diagnosis of an acute obstructive or perforative process of the small or large bowel.
Over the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). ...High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients.
A systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis.
Seven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively).
Immunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed.
PROSPERO (CRD42022333891).
Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects ...on the ADC and on the underlying pathology has not been adequately defined.
Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG).
Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients.
There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index.
Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.
Abstract Background Spindle cell carcinoma (SpCC) is an infrequent and aggressive type of squamous cell carcinoma (SCC) characterized by the proliferation of epithelial and mesenchymal components. ...Oral SCC in children is an extremely rare entity and the SpCC variant has been reported in one case in the paediatric patient literature. Methods In this paper, we report a case of SpCC of the tongue in an 11-year-old boy treated by on-block surgical resection and microvascular tissue reconstruction. Results After 14 months the patient is free of disease with easily intelligible speech and normal swallowing. Conclusions Diagnosis and treatment of this rare tumour in this age group is a challenge because of the overlapping of histopathological features and the complex reconstruction required to achieve adequate aesthetic and functional results.
Different guidelines for colorectal cancer (CRC) pathology reporting have been published. We aimed to identify differences between publicly available CRC reporting guidelines and to survey ...pathologists from different countries to establish the degree of guideline implementation in local routine practice. We compared all core and non-core items of CRC reporting guidelines to identify discrepancies. We then created a survey, which was sent out to 782 pathologists practicing in 30 different countries. It included questions on the demographics of the reporting pathologist as well as resection specimen handling and microscopic evaluation, grading, staging, and additional techniques, such as immunohistochemistry or molecular pathology. First, core and non-core items of five national CRC reporting guidelines were compared and 12 items were found to differ. Different items are considered core or non-core by different guidelines and more than one TNM staging edition was applied across guidelines. The survey was completed by 143 pathologists from 30 countries. We identified differences between local practice and guidelines with potential clinical impact, e.g., tumor budding was never reported by 28.7% of responders, although it has prognostic value for survival in stage II CRC. This is the first international study comparing CRC pathology reporting guidelines with real-world local practices. There are differences in CRC pathology reporting guidelines and in guideline implementation into local practice, both with potential impact on patient care. Harmonization of datasets, use of templates, and audits of local pathology practice are needed to ensure best possible quality of CRC pathology reporting.
Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings ...of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized.
Traditionally, bladder cancer has been classified based on histology features. Recently, some works have proposed a molecular classification of invasive bladder tumors. To determine whether ...proteomics can define molecular subtypes of muscle invasive urothelial cancer (MIUC) and allow evaluating the status of biological processes and its clinical value. 58 MIUC patients who underwent curative surgical resection at our institution between 2006 and 2012 were included. Proteome was evaluated by high-throughput proteomics in routinely archive FFPE tumor tissue. New molecular subgroups were defined. Functional structure and individual proteins prognostic value were evaluated and correlated with clinicopathologic parameters. 1,453 proteins were quantified, leading to two MIUC molecular subgroups. A protein-based functional structure was defined, including several nodes with specific biological activity. The functional structure showed differences between subtypes in metabolism, focal adhesion, RNA and splicing nodes. Focal adhesion node has prognostic value in the whole population. A 6-protein prognostic signature, associated with higher risk of relapse (5 year DFS 70% versus 20%) was defined. Additionally, we identified two MIUC subtypes groups. Prognostic information provided by pathologic characteristics is not enough to understand MIUC behavior. Proteomics analysis may enhance our understanding of prognostic and classification. These findings can lead to improving diagnosis and treatment selection in these patients.
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