Hepatocellular carcinoma (HCC) is one of the most frequent cancer types worldwide, with over half a million new cases diagnosed annually (1). The global burden of HCC is estimated to increase in the next two decades, and by 2030 it is predicted to be the second most common cause of cancer-related mortality worldwide (2). The prognosis for patients with advanced disease is poor and most patients survive only a few months following diagnosis. New insights into molecular biology of this fatal disease could lead to the identification of valuable molecular biomarkers for prediction of treatment response and for development of effective anticancer therapies.In the era of personalized medicine, research is focused on finding biomarkers based on DNA, RNA and proteins in groups of patients with similar molecular and genetic anomalies (3). RNAscope is a modern in situ hybridization (ISH) technology, compatible with the use of formalin-fixed paraffin-embedded (FFPE) tissue sections, that allows amplification of targeted-specific signals without amplifying the background (4). Compared to other RNA ISH methods, RNAscope is a highly sensitive and specific test and the ability to detect mRNA signals using standard microscopy makes it a powerful tool (4, 5).Podoplanin (PDPN), a mucin-type transmembrane protein, is expressed in a relatively large spectrum of tumours and its overexpression was found to be correlated with increased cancer cell motility and metastasis (6). However, the role of this protein in HCC tumour cells is uncertain. The purpose of the present study was to evaluate PDPN in HCC tumour cells by using both IHC and RNAscope, and to compare the sensitivity of these techniques in PDPN detection. Materials and MethodsPatients and tissue samples. A total of 20 patients, diagnosed with HCC and who underwent partial hepatectomy at the Regional Institute of Gastroenterology and Hepatology (Cluj-Napoca, Romania) were retrospectively studied. As controls, we used liver samples from five patients with liver metastases from colonic adenocarcinoma who underwent curative hepatic resection. The 383
Improved HER2 assessement is needed for urothelial carcinomas. HER2-IHC scored as 0-2 should be validated by and reclassified according to FISH analysis.
Background: The role of podoplanin (PDPN) and homebox prospero gene 1 (PROX1) in early stages of pancreatic islet changes induced by hypercaloric diet is unclear. The aim of this study was to study PDPN and PROX1 variability in pancreatic islets after a hypercaloric diet in a rat experimental model. Materials and Methods: Pancreatic biopsies harvested from Sprague-Dawley rats at 3, 6, and 9 weeks following hypercaloric diet intake were evaluated for morphological and molecular changes of Langerhans islets based on PDPN and PROX1 expression Results: Six weeks of hypercaloric diet induced hypertrophy of pancreatic islets with focal expression of Pdpn and Prox1 mRNA. At 9 weeks of hypercaloric diet, strong periinsular inflammation was found around hypertrophic islets highly expressing PDPN, and lacking Prox1 mRNA and protein expression. Conclusion: This is the first report of Pdpn and Prox1 mRNA expression variability and involvement in early steps of pancreatic islet changes following hypercaloric food intake.Obesity represents the leading cause of morbidity and mortality. The risk of developing obesity-related complications such as cardiovascular disease, stroke, type 2 diabetes and various types of cancer is increased in the obese population. More than 36.5% of US adults suffer from this chronic disease (1).Literature data show that obesity may favor lymphedema development and enhancement of inflammatory responses (2-5).Wang et al. demonstrated that homebox prospero gene 1 (PROX1) is necessary for endocrine progenitor formation and alpha cell differentiation and is expressed at high levels in all pancreatic endocrine progenitors (6). PROX1 is expressed in the adult pancreas at variable levels, with high values in the cells located in the islet mantle: α-cells, δ-cells, pancreatic polypeptide secreting cells, and ε-cells. It was found that PROX1 expression was required for β-cell differentiation (7). Paul et al., in a murine experimental model, demonstrated that high levels of PROX1 drastically impaired β-cell maturation and expansion (8).Well-known as a marker for lymphatic endothelial cells, podoplanin has been shown to be a diagnostic marker for many tumor types, such as seminoma, melanoma and squamous-cell carcinoma (9). Podoplanin-positive lymphatic vessels were reported in the pancreas of a single human fetus of 18 gestational weeks. The time of lymphatic colonization and interrelation with blood vessel formation in the pancreas is unknown (10). In normal tissues, podoplanin is a marker of basal cells in the layered epithelium of the skin and cervix, or is intensively expressed in several simple epithelia, such as the alveolar epithelium and the renal tubules (9). Podoplanin involvement in pancreatic development is less studied, and even lesser in diabetes-induced tissue damage. Few data have been reported regarding podoplanin expression in neuroendocrine carcinomas of pancreatic origin (9).Consequently, the aim of this work was to study podoplanin and PROX1 expression in normal and modified pancreatic ti...
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