1,721,190 research outputs found
The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumors: a comment on concepts and classification of mixed exocrine-endocrine neoplasms.
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Characterization of neuroendocrine tumors of the pancreas by real-time quantitative polymerase chain reaction. A methodological approach.
No full textThe aim of this study was to assess the suitability of using real-time quantitative PCR (RT-qPCR) to characterize neuroendocrine (NE) tumors of the pancreas. For a series of tumors, we evaluated several genes of interest, and the data were matched with the "classical" immunohistochemical (IHC) features. In 21 cases, we extracted RNA from formalin-fixed paraffin-embedded (FFPE) blocks, and in nine cases, we also extracted RNA from fresh-frozen tissue. The RT-qPCR procedure was performed using two sets of customized arrays. The test using the first set, covering 96 genes of interest, was focused on assessing the feasibility of the procedure, and the results were used to select 18 genes indicative of NE differentiation, clinical behavior, and therapeutic responsiveness for use in the second set of arrays. Threshold cycle (Ct) values were used to calculate the fold-changes in gene expression using the 2-â̂†â̂†Ct method. Statistical procedures were used to analyze the results, which were matched with the IHC and follow-up data. Material from fresh-frozen samples performed better in terms of the level of amplification, but acceptable and concordant results were also obtained from FFPE samples. In addition, high concordance was observed between the mRNA and protein expression levels of somatostatin receptor type 2A (R = 0.52, p = 0.016). Genes associated with NE differentiation, as well as the gastrin-releasing peptide receptor and O-6-methylguanine-DNA methyltransferase genes, were underexpressed, whereas angiogenesis-associated markers (CDH13 and SLIT2) were overexpressed in tissues with malignant behavior. The RT-qPCR procedure is practical and feasible in economic terms for the characterization of NE tumors of the pancreas and can complement morphological and IHC-based evaluations. Thus, the results of the RT-qPCR procedure might offer an objective basis for therapeutic choices
Goblet cell carcinoids and other mixed neuroendocrine/nonneuroendocrine neoplasms.
No full textWithin the spectrum of neuroendocrine tumors arising in different organs, intermediate and controversial entities exist displaying a coexistence of neuroendocrine and nonneuroendocrine cell populations, and that are grouped under terms such as "goblet cell carcinoid", "mixed endocrine-exocrine carcinoma", "combined carcinomas", or "adenocarcinoma with neuroendocrine differentiation". These tumors may display variable amounts of the two components, potentially ranging from I to 99%, and variable structural patterns, ranging from single scattered neuroendocrine cells to a well-defined neuroendocrine tumor cell component organized in typical organoid, trabecular, or solid growth patterns. Although variably included in the site-specific World Health Organization classification schemes, clear definitions and diagnostic features are still missing, as well as a definite knowledge of their biological properties and histogenesis. In the present report, the main characteristics of tumors showing mixed neuroendocrine and nonneuroendocrine features will be described, using morphological patterns and site of origin as schematic guidelines. Moreover, molecular and clinical aspects, which might help to understand their possible histogenesis and biological behavior, will be reviewed
Pathological and molecular features of adrenocortical carcinoma: An update
No full textThe pathological diagnosis of adrenocortical carcinoma (ACC), which is based on gross and microscopic criteria, is subjective. None of the features are absolutely indicative of malignancy, although their combination in a scoring system may correctly identify ACC. The Weiss system, which is currently the most popular, combines nine morphological parameters, of which three are structural ("dark" cytoplasm, diffuse architecture, necrosis), three are cytological (atypia, mitotic count, atypical mitotic figures) and three are related to invasion (of sinusoids, veins and tumour capsule). Although there are strictly defined criteria for each feature, some are straightforward and objective, while others are potentially more problematic (diffuse architecture, necrosis, sinusoidal, venous and capsular invasions). The classification of oncocytic and paediatric adrenocortical tumours is even more challenging, as not all of the above morphological parameters are predictors of malignancy in these tumour types. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC to identify reliable diagnostic and prognostic factors. Genetic and epigenetic alterations of p53, IGF-2 and molecules involved in cancer cell invasive properties seem the most promising. These molecular markers may not only play a role in the biology of these tumours and have prognostic implications, but may also be used as potential targets for treatment. However, these markers are not sufficiently sensitive and specific to replace conventional morphological criteria
Molecular Pathology of Poorly Differentiated and Anaplastic Thyroid Cancer: What Do Pathologists Need to Know?
Full text linkThe molecular characterization of poorly and anaplastic thyroid carcinomas has been greatly improved in the last years following the advent of high throughput technologies. However, with special reference to genomic data, the prevalence of reported alterations is partly affected by classification criteria. The impact of molecular pathology in these tumors is multifaceted and bears diagnostic, prognostic, and predictive implications although its use in the clinical practice is not completely assessed. Genomic profiling data claim that genetic alterations in poorly differentiated and anaplastic thyroid carcinomas include “Early” and “Late” molecular events, which are consistent with a multi-step model of progression. “Early” driver events are mostly RAS and BRAF mutations, whereas “Late” changes include above all TP53 and TERT promoter mutations, as well as dysregulation of gene involved in the cell cycle, chromatin remodeling, histone modifications, and DNA mismatch repair. Gene fusions are rare but represent relevant therapeutic targets. Epigenetic modifications are also playing a relevant role in poorly differentiated and anaplastic thyroid carcinomas, with altered regulation of either genes by methylation/deacetylation or non-coding RNAs. The biological effects of epigenetic modifications are not fully elucidated but interfere with a wide spectrum of cellular functions. From a clinical standpoint, the combination of genomic and epigenetic data shows that several molecular alterations affect druggable cellular pathways in poorly differentiated and anaplastic thyroid carcinomas, although the clinical impact of molecular typing of these tumors in terms of predictive biomarker testing is still under exploration
p63 expression as a new prognostic marker in Merkel cell carcinoma.
No full textBackground. Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor, mostly affecting elderly individuals. The histogenesis of this rare tumor as well as its prognostic criteria are a matter of dispute.
Methods. An immunohistochemical analysis of markers of proliferation (Ki-67/ MIB-1), neuroendocrine differentiation (chromogranin A and synaptophysin), and basal cell differentiation (p63) was performed in a series of 47 cases of MCC. The significance of pathologic data and of immunoreactivity with different markers was evaluated using the chi-square test. Survival curves were calculated using the Kaplan-Meyer method. The survival difference was estimated using the Wilcoxon or Mantel-Cox test.
Results. immunohistochemical evidence of neuroendocrine differentiation and immunopositivity for cytokeratin 20 were observed in all cases, whereas positivity for p63 was detected in approximately half of the cases (25 of 47 cases; 53.2%). Cases that were positive for p63 demonstrated a more aggressive clinical course than those that were negative (Z value of 2.93; P =.0003; hazards ratio of 22.22).
Conclusions. Data from the current study indicate that p63 expression is associated with a worse prognosis in patients with MCC and represents a new independent marker of clinical evolution
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
