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J. Mol. Pathol., Volume 5, Issue 3 (September 2024) – 6 articles

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15 pages, 2286 KiB  
Article
mRNA Expression Level of ALK in Neuroblastoma Is Associated with Histological Subtype, ALK Mutations and ALK Immunohistochemical Protein Expression
by Rixt S. Bruinsma, Marta F. Fiocco, Wendy W. J. de Leng, Lennart A. Kester, Karin P. S. Langenberg, Godelieve A. M. Tytgat, Max M. van Noesel, Marc H. W. A. Wijnen, Alida F. W. van der Steeg and Ronald R. de Krijger
J. Mol. Pathol. 2024, 5(3), 304-318; https://doi.org/10.3390/jmp5030022 - 1 Aug 2024
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Abstract
ALK is related to poor survival in neuroblastoma patients. We investigated the prognostic relevance of ALK mRNA expression and the relationship with ALK immunohistochemical expression, histological subtype and ALK aberrations. Whole transcriptome sequencing data were available from 54 patients. Overall survival (OS) and [...] Read more.
ALK is related to poor survival in neuroblastoma patients. We investigated the prognostic relevance of ALK mRNA expression and the relationship with ALK immunohistochemical expression, histological subtype and ALK aberrations. Whole transcriptome sequencing data were available from 54 patients. Overall survival (OS) and event-free survival (EFS) were estimated with Kaplan–Meier’s methodology. ALK protein expression was analyzed by immunohistochemistry. ALK aberrations were detected using whole exome sequencing, single nucleotide polymorphism array, next generation sequencing and/or fluorescence in situ hybridization. OS was 74.8% and EFS was 60%. ALK mRNA expression was not associated with OS (HR 1.127, 95% CI (0.812–1.854), p = 0.331) and adjusted EFS (HR 1.134, 95% CI (0.783–1.644), p = 0.505), but was associated with histological subtype (OR 1.914, 95% CI (1.083–3.382), p = 0.025) and ALK protein expression (negative versus weak: OR 2.829, 95% CI (1.290–6.204), p = 0.009) (negative versus moderate/strong: OR 2.934, 95% CI (0.889–9.679), p = 0.077). ALK mutated tumors had significantly higher ALK mRNA expression than non-mutated tumors (p < 0.001). MYCN-amplified neuroblastomas have higher MYCN mRNA expression (p ≤ 0.001), but not ALK mRNA expression (p = 0.553). ALK mRNA expression is higher in ALK mutated neuroblastomas and is associated with poorer differentiation degree and higher protein expression. ALK mRNA expression is not significantly associated with OS and EFS. Full article
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12 pages, 1163 KiB  
Article
Next-Generation-Sequencing of the Human B-Cell Receptor Improves Detection and Diagnosis and Enhances Disease Monitoring in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
by Chidimma Agatha Akpa, Cora Husemann, Chris Allen, Ann-Christin von Brünneck, Jana Ihlow and Michael Hummel
J. Mol. Pathol. 2024, 5(3), 292-303; https://doi.org/10.3390/jmp5030021 - 4 Jul 2024
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Abstract
Mucosa-associated lymphoid tissue (MALT) lymphomas are slow-growing B-cell lymphomas mainly diagnosed in the stomach and termed gastric MALT lymphoma (G-MALT). Despite histological evaluation, immunostaining, and additional B-cell clonality analysis by fragment analysis, a clear-cut diagnosis is not feasible in all cases, especially for [...] Read more.
Mucosa-associated lymphoid tissue (MALT) lymphomas are slow-growing B-cell lymphomas mainly diagnosed in the stomach and termed gastric MALT lymphoma (G-MALT). Despite histological evaluation, immunostaining, and additional B-cell clonality analysis by fragment analysis, a clear-cut diagnosis is not feasible in all cases, especially for clinical follow-up of patients after treatment. We examined clonally rearranged immunoglobulin heavy- and light-chain gene sequences of 36 genomic DNA samples from six different patients obtained at different time points over the course of several years using the OncomineTM B-cell receptor pan-clonality next-generation sequencing (NGS) assay. Each case consisted of samples diagnosed with G-MALT and samples without evidence of lymphoma, based on histological examinations. We show a robust correlation (100%) of the results between the applied NGS method and histology-diagnosed G-MALT-positive patients. We also detected malignant clonotypes in samples where histology assessment failed to provide clear evidence of G-MALT (15 out of 19 samples). Furthermore, this method revealed malignant clonotypes much earlier in the disease course, with NGS of the immunoglobulin light chain being crucial in complementing immunoglobulin heavy-chain analysis. Hence, the value of NGS in routine lymphoma diagnostics is greatly significant and can be explored in order to provide better diagnoses and proffer the early detection of lymphoma relapse. Full article
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16 pages, 8681 KiB  
Article
Insulin-Resistant Male LEW.1WR1 Rats Do Not Develop β-Cell Mass Expansion in Response to a Moderate Sucrose Diet
by Quiana C. Wilkerson-Vidal, Moses A. David, James Gerard Wolfsberger, Madushika M. Wimalarathne, Evann Fowler, John R. Diaz, Alexis Fink, Elijah S. Sterkel, Ian Ross, Bernhard Vogler and Sharifa T. Love-Rutledge
J. Mol. Pathol. 2024, 5(3), 276-291; https://doi.org/10.3390/jmp5030020 - 3 Jul 2024
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Abstract
Characterizing changes in beta cell function during prolonged hyperinsulinemia and dietary stress is important to study to prevent diseases like metabolic dysfunction-associated steatotic liver disease and insulin resistance. This research investigates how a moderate sucrose (MS) diet affects insulin resistance and β-cell mass [...] Read more.
Characterizing changes in beta cell function during prolonged hyperinsulinemia and dietary stress is important to study to prevent diseases like metabolic dysfunction-associated steatotic liver disease and insulin resistance. This research investigates how a moderate sucrose (MS) diet affects insulin resistance and β-cell mass in two rat strains: LEW.1WR1 and Wistar Furth (WF). LEW.1WR1 rats seem to be sensitive to beta cell disruptions as weanlings. Twenty-one male LEW.1WR1 rats and sixteen male WF rats were studied over 18 weeks. The rats were divided into groups and given either the control or MS diet. Their body weight was monitored twice a week. Insulin tolerance tests (ITTs) and fasting blood glucose measurements were taken at intervals. Urine samples were analyzed to assess metabolic shifts, and pancreas tissue was examined to evaluate changes in β-cell mass. The LEW.1WR1 rats became overweight and showed higher insulin resistance than the WF rats. Both strains of rats on the MS diet displayed changes in urine metabolite profiles in terms of levels of lactic acid and alanine. This study highlights the impact or lack thereof of a moderate sucrose diet on body mass, insulin resistance, and β-cell mass, with notable effects observed specifically in LEW.1WR1 rats. These findings contribute to our understanding of how dietary sugar intake can affect metabolism when observed in models sensitive to metabolic defects. Full article
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12 pages, 2017 KiB  
Review
DICER1 Tumor Syndrome: A Retrospective Review and Future Perspectives
by Gerardo Cazzato, Nadia Casatta, Carmelo Lupo, Giuseppe Ingravallo and Domenico Ribatti
J. Mol. Pathol. 2024, 5(3), 264-275; https://doi.org/10.3390/jmp5030019 - 1 Jul 2024
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Abstract
DICER1 syndrome, a rare autosomal dominant genetic disorder, stems from mutations in the DICER1 gene, disrupting RNA interference and leading to various tumors. These tumors, affecting organs like the lung, kidney, ovaries, and brain, pose diagnostic challenges due to diverse presentations. Understanding DICER1-associated [...] Read more.
DICER1 syndrome, a rare autosomal dominant genetic disorder, stems from mutations in the DICER1 gene, disrupting RNA interference and leading to various tumors. These tumors, affecting organs like the lung, kidney, ovaries, and brain, pose diagnostic challenges due to diverse presentations. Understanding DICER1-associated tumors, including pleuropulmonary blastoma, ovarian Sertoli–Leydig cell tumors, and others, is vital for early detection and management. Surgical resection, chemotherapy, and targeted therapies are primary treatment modalities, with genetic counseling playing a crucial role. Multidisciplinary care is essential for optimal management, offering hope for improved outcomes in affected individuals. Full article
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2 pages, 180 KiB  
Reply
Reply to Torlakovic, E.; Normanno, N. Comment on “Bisson et al. Novel Approach to Proficiency Testing Highlights Key Practice Variations in Cancer Biomarker Delivery. J. Mol. Pathol. 2024, 5, 1–10”
by Brandon S. Sheffield, Kassandra R. Bisson, Andrea Beharry, Michael D. Carter, Shaan Dudani, Jonathan M. Loree, Stephanie Snow, Jennifer R. Won, Stephen Yip and John G. Garratt
J. Mol. Pathol. 2024, 5(3), 262-263; https://doi.org/10.3390/jmp5030018 - 27 Jun 2024
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Abstract
We thank Drs [...] Full article
4 pages, 177 KiB  
Comment
Comment on Bisson et al. Novel Approach to Proficiency Testing Highlights Key Practice Variations in Cancer Biomarker Delivery. J. Mol. Pathol. 2024, 5, 1–10
by Emina Torlakovic and Nicola Normanno
J. Mol. Pathol. 2024, 5(3), 258-261; https://doi.org/10.3390/jmp5030017 - 27 Jun 2024
Cited by 1 | Viewed by 330
Abstract
We have read, with great interest, a recently published article by Bisson KR et al [...] Full article
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