1,721,982 research outputs found
Anatomical pathology and molecular biology
No full textViene valutato l'utilizzo presente e futuro della biologia molecolare in anatomia patologica.no availabl
The landscape of molecular alterations in pancreatic and small intestinal neuroendocrine tumours
No full textGastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) arise throughout the gut and feature varying biological behaviour and malignant potential. GEP-NENs include two genetically different entities, well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NEC). NECs are characterized by a dismal prognosis and by distinctive TP53 and RB1 inactivation which sets them apart from NETs. The latter, conversely, have a wide spectrum of aggressiveness and molecular alterations. Knowledge on their biology has recently expanded thanks to high-throughput studies focused on two important groups of well-differentiated neuroendocrine neoplasms: pancreatic (PanNETs) and small intestinal (SiNETs) tumours. PanNETs have been among the most studied also due to genetic syndromes featuring their onset. Research stemming from this observation has uncovered the inactivation of MEN1, VHL, TSC1/2, and the hyperactivation of the PI3K/mTOR pathway as distinctive biological features of these neoplasms. Next-Generation Sequencing added information on the role of telomere lengthening via ATRX/DAXX inactivation in a fraction of PanNETs, while other display shortened telomeres and recurrent chromosomal alterations. The data so far disclosed a heterogeneous combination of driver events, yet converging into four pathways including DNA damage repair, cell cycle regulation, PI3K/mTOR signalling and telomere maintenance. SiNETs showed a lesser relationship with mutational driver events, even in the case of familial cases. High throughput studies identified putative driver mutations in CDKN1 and APC which, however, were reported in a minor fraction (∼10%) of cases. Tumorigenesis of SiNETs seems to depend more on chromosomal alterations (loss of chromosome 8, gains at 4, 5 and 20) and epigenetic events, which converge to hyperactivate the PI3K/mTOR, MAPK and Wnt pathways. While calling for further integrative studies, these data lay previous and recent findings in a more defined frame and provide clinical research with several candidate markers for patient stratification and companion diagnostics
Molecular approach in human tumor investigation: oncogenes, tumor suppressor genes and DNA tumor polyomaviruses (review).
No full textMolecular analysis are useful for diagnosis, prognosis and follow-up of the patients, as well as for addressing therapeutic choices. Most of the molecular methods are based on the analysis of nucleic acids. The DNA and RNA methodologies of routine applicability include Southern and Northern hybridizations and polymerase chain reaction (PCR) techniques. Southern blot hybridization recognizes major DNA rearrangements, and detection of oncogenic viral sequences present in high copy number, whereas PCR-based methods allow the detection of gross chromosomal modifications, fine gene alterations and low amount of tumor virus footprints. PCR techniques also allow the analysis of the partially degraded nucleic acids from formalin-fixed paraffin-embedded tissues. We present an overview of the use of molecular techniques for the analysis, diagnosis, prognosis and follow-up of neoplastic diseases, using examples from our experience in both leukemias and solid tumors
Anatomia Patologica: Le Basi
No full textLibro di testo per studenti di medicina e professioni sanitari
Molecular Techniques in Oncologic Pathology
No full textMolecular techniques have already earned a place in the management of oncologic disorders. The requests of Clinical Oncologists to Pathologists include, besides the diagnosis, any additional information useful for prognosis and therapeutic choices, as well as expertise and technologies to follow-up patients. To fulfill these commitments, pathologists have been resorting to classical morphology, cytochemistry, immunocytochemistry, and have only recently come to include molecular genetic techniques. Most of the molecular methods of practical utility are based on the analysis of DNA. The DNA methodologies of routine applicability mainly include Southern blotting and polymerase chain reaction (PCR). Southern blotting recognizes major DNA rearrangements, whereas PCR-based methods allow to recognize both gross chromosomal modifications and fine gene alterations, including point mutations. PCR techniques may also be used for many purposes using the partially degraded DNA from formalin-fixed paraffin-embedded tissues. Here we will draw a brief overview of the role of molecular genetic techniques in the pathology practice for the diagnosis, prognosis and follow-up of neoplastic diseases, using examples from our experience in hematology and gastroenterology
Microsatellite instability in pancreatic and ampullary carcinomas: histology, molecular pathology and clinical implications
No full textMicrosatellite instability (MSI) / defective DNA mismatch repair (dMMR) represent an important molecular alteration with diagnostic, prognostic and predictive value. The increasing interest towards this genetic alteration is given to the high response rate of MSI/dMMR tumors to immunotherapy. There are different cancers in the periampullary region that can harbor MSI/dMMR, and significant morphological-molecular correlates should be acknowledged in this district: 1) Pancreatic ductal adenocarcinoma (PDAC): in this tumor category, the prevalence of MSI/dMMR is about 1-2%, and medullary and colloid variants are the most typically involved; 2) Ampullary adenocarcinoma: here the prevalence of MSI/dMMR is up to 18%. In this neoplastic group, MSI/dMMR is more commonly found in the intestinal subtype; 3) Pancreatic acinar cell carcinoma: here the prevalence of MSI/dMMR is up to 14%; 4) pancreatic and ampullary neuroendocrine carcinoma: in this tumor category, the prevalence of MSI/dMMR is up to 5-8%, and this molecular alteration should be assessed also in cases of mixed neuroendocrine-non neuroendocrine neoplasms. Given the clinical importance of MSI/dMMR and its not-negligible prevalence among the different carcinomas arising in this district, its assessment should become part of the routine diagnostic workflow at least for the most typical histotypes. The test of choice is represented by immunohistochemistry for PDAC and ampullary carcinomas, and by direct molecular analyses including MSI-based polymerase chain reaction and next-generation sequencing for acinar cell and neuroendocrine carcinomas
Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms
No full textGastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) are heterogeneous regarding site of origin, biological behavior and malignant potential. There has been a rapid increase in data publication over the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal NETs. This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NEC). NENs are graded as G1, G2 or G3 based on mitotic count and/or Ki-67 labelling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways including DNA damage repair, cell cycle regulation, PI3K/mTOR signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also due to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification and planning of personalized therapy
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