We used molecular anatomic pathology to determine the mutational status (loss of heterozygosity [LOH]) to make the distinction between reactive gliosis and glial neoplasia. LOH has been shown to be absent in reactive states and present in neoplastic cellular proliferations. Three groups of patient specimens were analyzed: group 1, reactive gliosis (n = 15); group 2, gliomas of varying histologic type and grade (n = 54); group 3, diagnostically challenging reactive gliosis vs glioma (n = 16). No group 1 cases (0/15 [0%]) showed allelic loss, whereas all high-grade glial neoplasms, a subset of group 2 (35/35 [100%]) manifested at least 1 allelic loss alteration, with most cases (33/35 [94%]) displaying 2 or more such changes. During a look forward at the group 3 patients, clinical history clarified the problematic diagnosis in a subset of 11 patients: 8 (73%) of 11 clinical outcomes were predicted correctly by our analysis. The molecular anatomic pathology approach outlined herein is designed for minute, formalin-fixed, paraffin-embedded specimens, which are encountered in everyday surgical pathology practice. Molecular anatomic pathology opens the possibilities of molecular analysis to everyday pathology practice.
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http://dx.doi.org/10.1309/WF2H-L03T-7YP7-13NK | DOI Listing |
IBRO Neurosci Rep
June 2025
Université de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, France.
It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring.
View Article and Find Full Text PDFAm J Surg Pathol
January 2025
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis.
View Article and Find Full Text PDFMol Neurodegener
January 2025
College of Life Sciences and Oceanography, Brain Disease and Big Data Research Institute, Shenzhen University, Shenzhen, 518060, Guangdong, China.
Background: Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.
Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are emerging as novel gene regulators, involved in various biological processes and human diseases.
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