1,721,015 research outputs found
Diagnostic, prognostic and predictive significance of the immunohistochemical loss of H3K27me3 in different CNS and extra-CNS tumors
Full text linkEpigenetic regulation is essential for normal development, influencing critical biological processes such as cell differentiation, tissue development, and responses to environmental factors. The epigenetic signature in cells is a dynamic process changing over time and adapting to internal and environmental stimuli. Dysregulation of these processes is associated with various diseases, including inflammatory and degenerative conditions, as well as cancers.
Indeed, several epigenetic changes have been implicated in cancer onset, progression, and in modulating the effectiveness of treatments, and the ongoing research in this field holds promise for developing novel therapeutic strategies targeting epigenetic mechanisms.
In recent years, among epigenetic modifications, dysregulation of the methylation status of the lysin at position 28 of Histone 3 (H3K27) has gained significant attention and loss of trimethylation of H3K27 (H3K27me3) has been extensively studied in various tumor types, in some of which it serves as a diagnostic and/or prognostic marker.
In this project we aimed to investigate the diagnostic, prognostic and predictive role of H3K27me3 immunohistochemical loss in different central nervous system (CNS) and extra-CNS tumors.
In diffuse intracranial gliomas, H3K27me3 loss was significantly correlated with the presence of 1p/19q codeletion and ATRX immunohistochemical retention, serving as a diagnostic marker in the differential diagnosis of IDH-mutant gliomas. In these tumors, H3K27me3 loss was also a prognostic marker, its loss being correlated with longer progression-free survival (PFS), independently of IDH1/2 mutations.
We demonstrated H3 K27me3 loss in rosette forming glioneuronal tumors (RGNTs), without any correlation with clinical outcome.
In intracranial meningiomas and rectal adenocarcinomas, H3 K27me3 loss was significantly associated with shorter PFS after radiotherapy, suggesting that this staining could be used as a predictive biomarker in these tumors.
Therefore, our data demonstrate that H3K27me3 loss has a different and opposite prognostic significance in different tumor types.
Despite the diagnostic, prognostic and predictive value of H3 K27me3 loss in human tumors, a standardized protocol for its assessment and interpretation is urgently needed for its use in routine practice
IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification
Full text link: According to the fifth edition of the World Health Organization (WHO) Classification, diffuse gliomas typically occurring in adults are classified as oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and glioblastoma IDH-wildtype. Among these, the former has the most favorable clinical course, whereas the latter has the worst prognosis. In IDH-mutant gliomas, the IDH1 p. R132H is the most frequent IDH mutation. Other mutations in IDH1 are rare and predominantly found in astrocytomas, whereas IDH2 mutations are mostly observed in oligodendrogliomas. Astrocytomas IDH-mutant display frequent immunohistochemical loss of ATRX, which is mutually exclusive with 1p/19q codeletion. They are graded based on histopathological features and the presence of CDKN2A/B homozygous deletion, whereas the criteria for grading oligodendrogliomas are less defined. DNA methylation profiling has recently shown three additional distinct tumor types among diffuse IDH-mutant gliomas: infratentorial astrocytoma IDH mutant; primary mismatch repair deficient IDH-mutant astrocytoma (PMRDIA); and oligosarcoma. Infratentorial astrocytoma IDH-mutant is enriched in IDH1 or IDH2 mutations that differ from the IDH1 p.R132H mutation and are detectable only by gene sequencing, displays less frequent ATRX loss and MGMT promoter methylation than supratentorial IDH-mutant astrocytomas, and may additionally harbor the H3 K27M mutation, which is typically found in H3 K27-altered diffuse midline glioma. PMRDIA occurs in the context of primary mismatch repair deficiency, is characterized by frequent MSH6 mutations, hypermutation, low frequency of MGMT promoter methylation, and poor clinical outcomes. Finally, oligosarcoma is a tumor featuring oligodendroglial and sarcomatous areas, and is characterized by worse outcome and frequent 1p/19q copy number loss of heterozygosity
Impairment of the Zn/Cd detoxification systems affects the ability of Salmonella to colonize Arabidopsis thaliana
Full text linkSalmonella capacity to colonize different environments depends on its ability to respond efficiently to fluctuations in micronutrient availability. Among micronutrients, Zn, besides playing an essential role in bacterial physiology, is a key element whose concentration can influence bacterial survival in a particular niche. Plant colonization by Salmonella enterica was described for several years, and some molecular determinants involved in this host-pathogen interaction have started to be characterized. However, it is still unclear if Zn plays a role in the outcome of this interaction, as well established for animal hosts that employ nutritional immunity strategies to counteract pathogens infections. In this study, we have investigated the involvement of Salmonella Typhimurium main effectors of zinc homeostasis in plant colonization, using Arabidopsis thaliana as a model host. The results show that to colonize plant tissues, Salmonella takes advantage of its ability to export excess metal through the efflux pumps ZntA and ZitB. In fact, the deletion of these Zn/Cd detoxification systems can affect bacterial persistence in the shoots, depending on metal availability in the plant tissues. The importance of Salmonella ability to export excess metal was enhanced in the colonization of plants grown in high Zn conditions. On the contrary, the bacterial disadvantage related to Zn detoxification impairment can be abrogated if the plant cannot efficiently translocate Zn to the shoots. Overall, our work highlights the role of Zn in Salmonella-plant interaction and suggests that modulation of plant metal content through biofortification may be an efficient strategy to control pathogen colonization
Parvalbumin immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney
No full textParvalbumin is a cytosolic calcium-binding protein expressed in the distal convoluted tubule of the renal nephron. Among epithelial renal tumors, the reactivity for parvalbumin is observed in chromophobe renal cell carcinomas and frequently in oncocytomas. On the other hand, there are no data available on parvalbumin expression in the mesenchymal tumors of the kidney. Therefore, the purpose of this study was to evaluate the expression of parvalbumin in the spectrum of PEC (perivascular epithelioid cells) lesions of the kidney. Sixty-six PEC lesions (37 classic angiomyolipomas, 10 microscopic angiomyolipomas, 7 epithelioid angiomyolipomas/pure epithelioid PEComas, 5 leiomyoma-like angiomyolipomas, 3 lipoma-like angiomyolipomas, 2 intraglomerular lesions, 1 angiomyolipoma with epithelial cysts (AMLEC), and 1 sclerosing angiomyolipoma) were immunohistochemically stained with parvalbumin. Overall, parvalbumin immunostain was found in fifty-six PEC lesions (85%) and absent in the remaining ten cases (15%). Classic angiomyolipomas were positive in almost all cases (97%). Intraglomerular lesions and AMLEC showed parvalbumin immunolabeling as well. None of the 7 epithelioid angiomyolipomas/pure epithelioid PEComas or the only sclerosing angiomyolipoma expressed parvalbumin. In conclusion, we demonstrated the immunolabeling of parvalbumin in almost all PEC lesions of the kidney, but not in the epithelioid angiomyolipoma/pure epithelioid PEComa. This finding could shed light on some biological characteristics observed in the PEC lesions such as the plasticity of their cellular component. Moreover, parvalbumin may be another useful tool in the differential diagnosis among epithelioid angiomyolipoma/pure epithelioid PEComa with other renal eosinophilic tumors, such as oncocytoma and chromophobe renal cell carcinoma
Surgical treatment of ductal biliary recurrence of poorly cohesive gastric cancer mimicking primary biliary tract cancer: a case report
No full text: Ductal biliary recurrence of cancers arising in other anatomical districts is a rare event, usually observed in the setting of disseminated disease; hence surgery is rarely a viable option. We present the case of a 56-year-old male who underwent subtotal gastric resection 7 years earlier for a poorly cohesive gastric cancer, presenting with obstructive jaundice. Magnetic resonance imaging and computed tomography scan suggested primary malignant obstruction of the main bile duct. Percutaneous transhepatic biliary drainage was performed to palliate jaundice and obtain biopsies; pathological examination suggested a ductal biliary recurrence of gastric carcinoma. Pancreaticoduodenectomy and bile duct resection were performed. Histology, immunohistochemistry and molecular profiling confirmed that the stenosis represented a gastric cancer metastasis. This is the first case of an isolated ductal biliary recurrence of gastric cancer amenable to surgical resection. This clinical case suggests that biliary obstructions in patients with previous oncological history require biliary biopsies to exclude a recurrent disease
H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall
Full text linkAccording to the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS), diffuse midline glioma H3 K27-altered is a grade 4 infiltrative glioma that arises from midline anatomical structures and is characterized by the loss of H3 K27me3 and co-occurring H3 K27M mutation or EZHIP overexpression. However, the H3 K27M mutation has also been observed in circumscribed gliomas and glioneuronal tumors arising in midline anatomical structures, which may result in diagnostic pitfalls.Rosette-forming glioneuronal tumor (RGNT) is a CNS WHO grade 1 neoplasm that histologically features neurocytic and glial components and originates in midline anatomical structures.This study aimed to assess whether RGNTs, similar to other midline tumors, may exhibit immunohistochemical loss of H3 K27me3 and harbor the H3 K27M mutation.All seven analyzed RGNTs displayed immunohistochemical loss of H3 K27me3 in all tumor cells or H3 K27me3 mosaic immunostaining. In one case, H3 K27me3 loss was associated with the H3 K27M mutation, whereas the other six cases did not exhibit any H3 mutations or EZHIP overexpression. During a follow-up period of 23 months, the H3 K27M-mutant case remained unchanged in size despite partial resection, indicating that the H3 mutation may not confer higher biological aggressiveness to RGNT.The immunohistochemical loss of H3 K27me3 co-occurring with the H3 K27M mutation may result in the potential misdiagnosis of RGNT, especially in cases of small biopsy specimens consisting of only the glial component
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