Purpose: KRAS, P16, TP53, and SMAD4/DPC4 mutations are common in pancreatic ductal adenocarcinoma (PDAC). The study aimed to evaluate the association between gene mutations in pre-treatment endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples and clinical outcomes of patients with PDAC.
Methods: There were 43 patients with resectable (R) PDAC and 41 patients with borderline resectable (BR) PDAC. CDKN2A/p16, TP53, and SMAD4/DPC4 were evaluated through immunohistochemistry (IHC) of pretreatment EUS-FNA (n = 84) and resected specimens (n = 71). All patients received neoadjuvant therapy.
Results: IHC of EUS-FNA specimens revealed p16 loss in 61 (73%), abnormal p53 in 61 (73%), and Smad4 loss in 38 (45%) patients. Abnormal p53 was associated with a lower resection rate (p = .017). Abnormal p53 and Smad4 loss were associated with recurrence within 6 months post-pancreatectomy (p = .03, p = .03, respectively). Univariate Cox regression analysis was conducted to reveal that abnormal p53 (p = .07), p16 loss and abnormal p53 (p = .04), and Smad4 and p16 loss (p = .03) were associated with poor prognosis.
Conclusions: Pre-treatment abnormal labeling of p53 in EUS-FNA specimen was associated with a lower resection rate and an early recurrence in R or BR PDAC cases.
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http://dx.doi.org/10.1002/jhbp.1286 | DOI Listing |
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
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Basic Medical College of Shaanxi University of Chinese Medicine,Xianyang,Shaanxi 712046,China.
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Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging.
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View Article and Find Full Text PDFBiomolecules
December 2024
Department of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa Street 7, 30-387 Krakow, Poland.
Melanoma cells remain resistant to chemotherapy with cisplatin (CisPt) and doxorubicin (DOX). The abnormal expression of Receptor-Interacting Protein Kinase 4 (RIPK4) in certain melanomas contributes to tumour growth through the NFκB and Wnt/β-catenin signalling pathways, which are known to regulate chemoresistance and recurrence. Despite this, the role of RIPK4 in response to chemotherapeutics in melanoma has not been reported.
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