Background: anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several malignancies, with prognostic and therapeutic implications. However, few studies investigated the correlation between ALK altered expression and prognosis in patients with glioblastoma (GBM).
Methods: We performed an evaluation of ALK overexpression and structural/quantitative chromosome alterations through immune-histochemical assay (IHC with D5F3 antibody) and fluorescent in situ hybridization (FISH) in patients with isocitrate dehydrogenase (IDH) wild type (wt) GBM. Assuming an ALK overexpression in 20 % of patients we planned a sample of 44 patients to achieve a probability of 90 % to include from 10 % to 30 % of patients with ALK alterations.
Results: We evaluated 44 patients with IDH wt GBM, treated in our institution and dead due to GBM progression in 2017. ALK overexpression obtained by a composed score (the product of IHC intensity staining and rate of positive cells) was observed in 19 (43 %) patients. FISH analysis showed that 11 patients (25 %) had gene deletion, 2 patients (4.5 %) had monosomy and one patient (2.3 %) presented polysomy. Only one patient (2.3 %) demonstrated ALK rearrangement. There was no statistical difference in median OS between patients with ALK-positive (mOS = 18.9 months) and ALK-negative IHC (mOS = 18.0 months).
Conclusion: We identified some rare previously unreported alterations of ALK gene in patients with IDH wt GBM. In these patients, the ALK overexpression does not influences survival.
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http://dx.doi.org/10.1016/j.prp.2021.153447 | DOI Listing |
Int J Surg Pathol
January 2025
Department of Pathology, VCU School of Medicine, Richmond, VA, USA.
The proliferation of recognized neoplasms related to related to rearrangements involving kinase genes, arising in diverse somatic tissue lineages, poses an increasing challenge in surgical pathology. For instance, ALK rearrangements have been observed in diverse neoplasms of epithelial, connective tissue, and hematolymphoid lineages, many of which are associated with overexpression of ALK by immunohistochemistry as a useful biomarker. An even higher order challenge and pitfall would be the scenario where a tumor an ALK rearrangement nonetheless overexpresses the protein, thereby simulating an ALK-defined neoplasm.
View Article and Find Full Text PDFFront Oncol
December 2024
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium.
Introduction: The transcriptomic characteristics of + non-small cell lung cancer (NSCLC) represent a crucial aspect of its tumor biology. These features provide valuable insights into key dysregulated pathways, potentially leading to the discovery of novel targetable alterations or biomarkers.
Methods: From The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, all available + (n = 10), + (n = 5) and + (n = 5) NSCLC tumor and + cell line (n = 7) RNA-sequencing files were collected.
Stem Cell Reports
December 2024
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic address:
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that results in motor, sensory, cognitive, and affective deficits. Hippocampal demyelination, a common occurrence in MS, is linked to impaired cognitive function and mood. Despite this, the precise mechanisms underlying cognitive impairments in MS remain elusive.
View Article and Find Full Text PDFVirchows Arch
December 2024
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor.
View Article and Find Full Text PDFCancers (Basel)
October 2024
Department of General Surgery, Medical University of Vienna and Gastroesophageal Tumor Unit, Comprehensive Cancer Center (CCC), 1090 Vienna, Austria.
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