Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Eliana Amato
Based on 6 articles published since 2010
(Why 6 articles?)
||||

Between 2010 and 2020, Eliana Amato wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Molecular alterations associated with metastases of solid pseudopapillary neoplasms of the pancreas. 2019

Amato, Eliana / Mafficini, Andrea / Hirabayashi, Kenichi / Lawlor, Rita T / Fassan, Matteo / Vicentini, Caterina / Barbi, Stefano / Delfino, Pietro / Sikora, Katarzyna / Rusev, Borislav / Simbolo, Michele / Esposito, Irene / Antonello, Davide / Pea, Antonio / Sereni, Elisabetta / Ballotta, Maria / Maggino, Laura / Marchegiani, Giovanni / Ohike, Nobuyuki / Wood, Laura D / Salvia, Roberto / Klöppel, Günter / Zamboni, Giuseppe / Scarpa, Aldo / Corbo, Vincenzo. ·ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, Tokai University School of Medicine, Isehara, Japan. · Institute of Pathology, Heinrich-Heine-University and University Hospital of Düsseldorf, Düsseldorf, Germany. · Department of Surgery, General Surgery B, University of Verona, Verona, Italy. · Section of Anatomic Pathology, Azienda Ospedaliera Rovigo, Rovigo, Italy. · Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Technical University Munich, Munich, Germany. · Division of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·J Pathol · Pubmed #30306561.

ABSTRACT: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare, low-grade malignant neoplasms that metastasise to the liver or peritoneum in 10-15% of cases. They almost invariably present somatic activating mutations of CTNNB1. No comprehensive molecular characterisation of metastatic disease has been conducted to date. We performed whole-exome sequencing and copy-number variation (CNV) analysis of 10 primary SPN and comparative sequencing of five matched primary/metastatic tumour specimens by high-coverage targeted sequencing of 409 genes. In addition to CTNNB1-activating mutations, we found inactivating mutations of epigenetic regulators (KDM6A, TET1, BAP1) associated with metastatic disease. Most of these alterations were shared between primary and metastatic lesions, suggesting that they occurred before dissemination. Differently from mutations, the majority of CNVs were not shared among lesions from the same patients and affected genes involved in metabolic and pro-proliferative pathways. Immunostaining of 27 SPNs showed that loss or reduction of KDM6A and BAP1 expression was significantly enriched in metastatic SPNs. Consistent with an increased transcriptional response to hypoxia in pancreatic adenocarcinomas bearing KDM6A inactivation, we showed that mutation or reduced KDM6A expression in SPNs is associated with increased expression of the HIF1α-regulated protein GLUT1 at both primary and metastatic sites. Our results suggest that BAP1 and KDM6A function is a barrier to the development of metastasis in a subset of SPNs, which might open novel avenues for the treatment of this disease. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

2 Article Whole-genome landscape of pancreatic neuroendocrine tumours. 2017

Scarpa, Aldo / Chang, David K / Nones, Katia / Corbo, Vincenzo / Patch, Ann-Marie / Bailey, Peter / Lawlor, Rita T / Johns, Amber L / Miller, David K / Mafficini, Andrea / Rusev, Borislav / Scardoni, Maria / Antonello, Davide / Barbi, Stefano / Sikora, Katarzyna O / Cingarlini, Sara / Vicentini, Caterina / McKay, Skye / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / McLean, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Wilson, Peter J / Anderson, Matthew J / Fink, J Lynn / Newell, Felicity / Waddell, Nick / Holmes, Oliver / Kazakoff, Stephen H / Leonard, Conrad / Wood, Scott / Xu, Qinying / Nagaraj, Shivashankar Hiriyur / Amato, Eliana / Dalai, Irene / Bersani, Samantha / Cataldo, Ivana / Dei Tos, Angelo P / Capelli, Paola / Davì, Maria Vittoria / Landoni, Luca / Malpaga, Anna / Miotto, Marco / Whitehall, Vicki L J / Leggett, Barbara A / Harris, Janelle L / Harris, Jonathan / Jones, Marc D / Humphris, Jeremy / Chantrill, Lorraine A / Chin, Venessa / Nagrial, Adnan M / Pajic, Marina / Scarlett, Christopher J / Pinho, Andreia / Rooman, Ilse / Toon, Christopher / Wu, Jianmin / Pinese, Mark / Cowley, Mark / Barbour, Andrew / Mawson, Amanda / Humphrey, Emily S / Colvin, Emily K / Chou, Angela / Lovell, Jessica A / Jamieson, Nigel B / Duthie, Fraser / Gingras, Marie-Claude / Fisher, William E / Dagg, Rebecca A / Lau, Loretta M S / Lee, Michael / Pickett, Hilda A / Reddel, Roger R / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Epari, Krishna / Nguyen, Nam Q / Zeps, Nikolajs / Falconi, Massimo / Simbolo, Michele / Butturini, Giovanni / Van Buren, George / Partelli, Stefano / Fassan, Matteo / Anonymous6880896 / Khanna, Kum Kum / Gill, Anthony J / Wheeler, David A / Gibbs, Richard A / Musgrove, Elizabeth A / Bassi, Claudio / Tortora, Giampaolo / Pederzoli, Paolo / Pearson, John V / Waddell, Nicola / Biankin, Andrew V / Grimmond, Sean M. ·ARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. · QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. · Medical Oncology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, General Hospital of Treviso, Department of Medicine, University of Padua, Italy. · Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy. · The University of Queensland, School of Medicine, Brisbane 4006, Australia. · Pathology Queensland, Brisbane 4006, Australia. · Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Brisbane 4006, Australia. · Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. · School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Centre for Cancer Bioinformatics, Peking University Cancer Hospital &Institute, Beijing 100142, China. · Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. · Department of Anatomical Pathology. St Vincent's Hospital, Sydney, New South Wales 2010, Australia. · Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. · Department of Pathology, Queen Elizabeth University Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. · Michael E. DeBakey Department of Surgery and The Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3411, USA. · Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia. · Children's Medical Research Institute, The University of Sydney, Westmead, New South Wales 2145, Australia. · Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. · University of Sydney. Sydney, New South Wales 2006, Australia. · Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. · School of Medicine, Western Sydney University, Penrith, New South Wales 2175, Australia. · Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. · School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia 6009, Australia. · St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. · Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. · University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, 3010, Victoria, Australia. ·Nature · Pubmed #28199314.

ABSTRACT: The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

3 Article RASSF1 tumor suppressor gene in pancreatic ductal adenocarcinoma: correlation of expression, chromosomal status and epigenetic changes. 2016

Amato, Eliana / Barbi, Stefano / Fassan, Matteo / Luchini, Claudio / Vicentini, Caterina / Brunelli, Matteo / Malleo, Giuseppe / Scarpa, Aldo / Malpeli, Giorgio. ·ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. eliana.amato@gmail.com. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. stefano.barbi@univr.it. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. matteo.fassan@gmail.com. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. claudio.luchini@univr.it. · Department of Pathology, The Hospital and University of Verona, Verona, Italy. claudio.luchini@univr.it. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. caterinavicentini@hotmail.it. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. matteo.brunelli@univr.it. · Department of Surgery and Oncology, The Hospital and University of Verona, Verona, Italy. giuseppe.malleo@ospedaleuniverona.it. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. aldo.scarpa@univr.it. · Department of Pathology, The Hospital and University of Verona, Verona, Italy. aldo.scarpa@univr.it. · ARC-NET Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, The Hospital and University of Verona, Verona, Italy. giorgio.malpeli@univr.it. · Department of Surgery and Oncology, The Hospital and University of Verona, Verona, Italy. giorgio.malpeli@univr.it. ·BMC Cancer · Pubmed #26754001.

ABSTRACT: BACKGROUND: The Ras Association Domain Family Member 1 (RASSF1) is one of the most frequently reported methylation-inactivated tumor suppressor genes in primary pancreatic ductal adenocarcinomas (PDAC). Limited information is still available about the impact of RASSF1 gene silencing on the expression of its different isoforms in neoplastic cells. METHODS: A series of 96 primary PDAC, with known clinico-pathological parameters, was tested for RASSF1 methylation status by methylation-specific PCR, RASSF1 locus copy number alterations by fluorescence in situ hybridization, and Rassf1a protein expression by immunohistochemistry. A further series of 14 xenografted primary PDAC and 8 PDAC-derived cell lines were tested to obtain a detailed methylation mapping of CpG islands A and C of the RASSF1 locus by pyrosequencing and to evaluate the expression of Rassf1 variants by qRT-PCR. RESULTS: Methylation of CpG island A of the RASSF1 gene was observed in 35% of the tumors and allelic loss of RASSF1 locus was seen in 30 disomic and in 20 polysomic cases (52%). Rassf1a immunohistochemical expression was downregulated in half of primary PDAC, and this downregulation was neither correlated with methylation of RASSF1 promoter nor with RASSF1 copy number alterations. RASSF1 status did not influence patients' prognosis. The expression of the seven RASSF1 isoforms in xenografts and cell lines showed that RASSF1A, RASSF1B, and RASSF1C isoforms were present in all xenografts and cell lines, whereas RASSF1D, RASSF1E, and RASSF1F isoforms were variably expressed among samples. RASSF1G was never expressed in either xenografts or cell lines. The variable expression of RASSF1 isoforms in PDAC xenografts and cell lines was not dependent on RASSF1 methylation status of CpG islands A and C. CONCLUSIONS: RASSF1 alterations occurring in PDAC mainly consist in variations of expression of the different isoforms. Different genetic mechanisms seem to contribute to RASSF1 deregulation in this setting, but RASSF1 methylation does not seem to substantially affect RASSF1 isoforms expression.

4 Article Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. 2014

Amato, Eliana / Molin, Marco Dal / Mafficini, Andrea / Yu, Jun / Malleo, Giuseppe / Rusev, Borislav / Fassan, Matteo / Antonello, Davide / Sadakari, Yoshihiko / Castelli, Paola / Zamboni, Giuseppe / Maitra, Anirban / Salvia, Roberto / Hruban, Ralph H / Bassi, Claudio / Capelli, Paola / Lawlor, Rita T / Goggins, Michael / Scarpa, Aldo. ·ARC-Net Research Centre and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Italy. ·J Pathol · Pubmed #24604757.

ABSTRACT: Intraductal neoplasms are important precursors to invasive pancreatic cancer and provide an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging, as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized. Fifty-two intraductal papillary neoplasms, including 48 intraductal papillary mucinous neoplasms (IPMNs) and four intraductal tubulopapillary neoplasms (ITPNs), were subjected to the mutation assessment in 51 cancer-associated genes, using ion torrent semiconductor-based next-generation sequencing. P16 and Smad4 immunohistochemistry was performed on 34 IPMNs and 17 IPMN-associated carcinomas. At least one somatic mutation was observed in 46/48 (96%) IPMNs; 29 (60%) had multiple gene alterations. GNAS and/or KRAS mutations were found in 44/48 (92%) of IPMNs. GNAS was mutated in 38/48 (79%) IPMNs, KRAS in 24/48 (50%) and these mutations coexisted in 18/48 (37.5%) of IPMNs. RNF43 was the third most commonly mutated gene and was always associated with GNAS and/or KRAS mutations, as were virtually all the low-frequency mutations found in other genes. Mutations in TP53 and BRAF genes (10% and 6%) were only observed in high-grade IPMNs. P16 was lost in 7/34 IPMNs and 9/17 IPMN-associated carcinomas; Smad4 was lost in 1/34 IPMNs and 5/17 IPMN-associated carcinomas. In contrast to IPMNs, only one of four ITPNs had detectable driver gene (GNAS and NRAS) mutations. Deep sequencing DNA from seven cyst fluid aspirates identified 10 of the 13 mutations detected in their associated IPMN. Using next-generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms.

5 Article Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors. 2011

Malpeli, Giorgio / Amato, Eliana / Dandrea, Mario / Fumagalli, Caterina / Debattisti, Valentina / Boninsegna, Letizia / Pelosi, Giuseppe / Falconi, Massimo / Scarpa, Aldo. ·Department of Pathology and Diagnostics, University of Verona, Verona, Italy. giorgio.malpeli@univr.it ·BMC Cancer · Pubmed #21838870.

ABSTRACT: BACKGROUND: RASSF1A gene silencing by DNA methylation has been suggested as a major event in pancreatic endocrine tumor (PET) but RASSF1A expression has never been studied. The RASSF1 locus contains two CpG islands (A and C) and generates seven transcripts (RASSF1A-RASSF1G) by differential promoter usage and alternative splicing. METHODS: We studied 20 primary PETs, their matched normal pancreas and three PET cell lines for the (i) methylation status of the RASSF1 CpG islands using methylation-specific PCR and pyrosequencing and (ii) expression of RASSF1 isoforms by quantitative RT-PCR in 13 cases. CpG island A methylation was evaluated by methylation-specific PCR (MSP) and by quantitative methylation-specific PCR (qMSP); pyrosequencing was applied to quantify the methylation of 51 CpGs also encompassing those explored by MSP and qMSP approaches. RESULTS: MSP detected methylation in 16/20 (80%) PETs and 13/20 (65%) normal pancreas. At qMSP, 11/20 PETs (55%) and 9/20 (45%) normals were methylated in at least 20% of RASSF1A alleles.Pyrosequencing showed variable distribution and levels of methylation within and among samples, with PETs having average methylation higher than normals in 15/20 (75%) cases (P = 0.01). The evaluation of mRNA expression of RASSF1 variants showed that: i) RASSF1A was always expressed in PET and normal tissues, but it was, on average, expressed 6.8 times less in PET (P = 0.003); ii) RASSF1A methylation inversely correlated with its expression; iii) RASSF1 isoforms were rarely found, except for RASSF1B that was always expressed and RASSF1C whose expression was 11.4 times higher in PET than in normal tissue (P = 0.001). A correlation between RASSF1A expression and gene methylation was found in two of the three PET cell lines, which also showed a significant increase in RASSF1A expression upon demethylating treatment. CONCLUSIONS: RASSF1A gene methylation in PET is higher than normal pancreas in no more than 75% of cases and as such it cannot be considered a marker for this neoplasm. RASSF1A is always expressed in PET and normal pancreas and its levels are inversely correlated with gene methylation. Isoform RASSF1C is overexpressed in PET and the recent demonstration of its involvement in the regulation of the Wnt pathway points to a potential pathogenetic role in tumor development.

6 Article Chromosome 3p alterations in pancreatic endocrine neoplasia. 2011

Amato, Eliana / Barbi, Stefano / Malpeli, Giorgio / Bersani, Samantha / Pelosi, Giuseppe / Capelli, Paola / Scarpa, Aldo. ·ARC-NET Center for Applied Research on Cancer, Hospital Concern and University School of Medicine, Verona, Italy. ·Virchows Arch · Pubmed #20981439.

ABSTRACT: Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes.