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Introduction: Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has ...
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Introduction: Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace.Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy.Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.
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In this article, various omics technologies and their applications in renal pathology (native and transplant biopsies) are reviewed and discussed. Despite significant progress and novel insights derived from these applications, ex...
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In this article, various omics technologies and their applications in renal pathology (native and transplant biopsies) are reviewed and discussed. Despite significant progress and novel insights derived from these applications, extensive adoption of molecular diagnostics in renal pathology has not been accomplished. Further validation of specific applications leading to increased diagnostic precision in a clinically relevant way is ongoing.
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In the past three years, remarkable discoveries have added three new human polyomaviruses (KI virus (KIV), WU virus (WUV) and Merkel cell virus (MCV)) to a class that previously had only two disease-causing members (BK virus (BKV)...
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In the past three years, remarkable discoveries have added three new human polyomaviruses (KI virus (KIV), WU virus (WUV) and Merkel cell virus (MCV)) to a class that previously had only two disease-causing members (BK virus (BKV) and JC virus (JCV)) identified. Two monkey polyomaviruses, simian virus (SV)40 and B-cell lymphotropic polyomavirus (LPV) are also present in humans. KIV and WUV lack the agnoprotein coding sequence and regulatory micro (mi)RNA clusters of BKV, JCV and SV40. MCV lacks the agnoprotein sequence but generates miRNAs. KIV, WUV and MCV are all widespread in humans. Although they have distinctive tissue tropisms, all these viruses are probably acquired in childhood. Of these viruses, only MCV has thus far been strongly linked to cancer. Marshalled evidence from diverse sources implicates MCV as an etiological agent of Merkel cell carcinoma. This review compares the structural features of the new and previously known polyomaviruses, with the aim of identifying approaches to molecular pathology.
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In the past three years, remarkable discoveries have added three new human polyomaviruses (KI virus (KIV), WU virus (WUV) and Merkel cell virus (MCV)) to a class that previously had only two disease-causing members (BK virus (BKV)...
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In the past three years, remarkable discoveries have added three new human polyomaviruses (KI virus (KIV), WU virus (WUV) and Merkel cell virus (MCV)) to a class that previously had only two disease-causing members (BK virus (BKV) and JC virus (JCV)) identified. Two monkey polyomaviruses, simian virus (SV)40 and B-cell lymphotropic polyomavirus (LPV) are also present in humans. KIV and WUV lack the agnoprotein coding sequence and regulatory micro (mi)RNA clusters of BKV, JCV and SV40. MCV lacks the agnoprotein sequence but generates miRNAs. KIV, WUV and MCV are all widespread in humans. Although they have distinctive tissue tropisms, all these viruses are probably acquired in childhood. Of these viruses, only MCV has thus far been strongly linked to cancer. Marshalled evidence from diverse sources implicates MCV as an etiological agent of Merkel cell carcinoma. This review compares the structural features of the new and previously known polyomaviruses, with the aim of identifying approaches to molecular pathology.
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Assessing malignant tumors for expression of multiple biomarkers provides data that are critical for patient management. Quantum dot-conjugated probes to specific biomarkers are powerful tools that can be applied in a multiplex ma...
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Assessing malignant tumors for expression of multiple biomarkers provides data that are critical for patient management. Quantum dot-conjugated probes to specific biomarkers are powerful tools that can be applied in a multiplex manner to single tissue sections of biopsies to measure expression levels of multiple biomarkers.
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Aims Whereas current cancer diagnosis largely relies on the well-established organ and tissue typing of tumours, partially complemented by molecular properties, the comprehensive molecular profiling efforts of recent years have st...
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Aims Whereas current cancer diagnosis largely relies on the well-established organ and tissue typing of tumours, partially complemented by molecular properties, the comprehensive molecular profiling efforts of recent years have stimulated proposals for molecular reclassifications of tumours independently of anatomical origin. Proposals based only on mutational profiles show the least concordance with histotypes, whereas greater concordance is achieved when various genomic and proteomic data are included. Methods and results The most comprehensive molecular reclassification of tumours, by Hoadley et al (Cell, 158, 2014; 929) and Hoadley et al (Cell, 173, 2018; 291), integrated multi-omics data, and proposes novel molecular tumour classes. To investigate the relationship between the proposed molecular classes and the original histological tumour types, we re-examined the histomorphology of molecularly reclassified cases. Our results show that the claimed molecular reclassification is associated with and explainable by specific histological subtypes in 70% of the reclassified cases. Conclusion Therefore, in contrast to the proclaimed reclassification and independence of molecular and histological tumour types, our analysis demonstrates that comprehensive molecular profiling, which includes gene expression and methylation as well as proteomic profiling in addition to mutational analyses, is largely consistent with histomorphological tumour properties.
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Pathology is the medical specialty concerned with the study of the disease nature and causes, playing a key role in bridging basic researches and clinical medicine. In the course of development, pathology has significantly expande...
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Pathology is the medical specialty concerned with the study of the disease nature and causes, playing a key role in bridging basic researches and clinical medicine. In the course of development, pathology has significantly expanded our understanding of disease, and exerted enormous impact on the management of patients. However, challenges facing pathology, the inherent invasiveness of pathological practice and the persistent concerns on the sample representativeness, constitute its limitations. Molecular imaging is a noninvasive technique to visualize, characterize, and measure biological processes at the molecular level in living subjects. With the continuous development of equipment and probes, molecular imaging has enabled an increasingly precise evaluation of pathophysiological changes. A new pathophysiology visualization system based on molecular imaging is forming and shows the great potential to reform the pathological practice. Several improvements in "trans-," including trans-scale, transparency, and translation, would be driven by this new kind of pathological practice. Pathological changes could be evaluated in a trans-scale imaging mode; tissues could be transparentized to better present the underlying pathophysiological information; and the translational processes of basic research to the clinical practice would be better facilitated. Thus, transpathology would greatly facilitate in deciphering the pathophysiological events in a multiscale perspective, and supporting the precision medicine in the future.
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Repositories containing high quality human biospecimens linked with robust and relevant clinical and pathological information are required for the discovery and validation of biomarkers for disease diagnosis, progression and respo...
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Repositories containing high quality human biospecimens linked with robust and relevant clinical and pathological information are required for the discovery and validation of biomarkers for disease diagnosis, progression and response to treatment. Current molecular based discovery projects using either low or high throughput technologies rely heavily on ready access to such sample collections. It is imperative that modern biobanks align with molecular diagnostic pathology practices not only to provide the type of samples needed for discovery projects but also to ensure requirements for ongoing sample collections and the future needs of researchers are adequately addressed. Biobanks within comprehensive molecular pathology programmes are perfectly positioned to offer more than just tumour derived biospecimens; for example, they have the ability to facilitate researchers gaining access to sample metadata such as digitised scans of tissue samples annotated prior to macrodissection for molecular diagnostics or pseudoanonymised clinical outcome data or research results retrieved from other users utilising the same or overlapping cohorts of samples. Furthermore, biobanks can work with molecular diagnostic laboratories to develop standardised methodologies for the acquisition and storage of samples required for new approaches to research such as 'liquid biopsies' which will ultimately feed into the test validations required in large pro-spective clinical studies in order to implement liquid biopsy approaches for routine clinical practice. We draw on our experience in Northern Ireland to discuss how this harmonised approach of biobanks working synergistically with molecular pathology programmes is a key for the future success of precision medicine. (C) 2016 Elsevier Ltd. All rights reserved.
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Molecular analysis is here to stay in diagnostic histopathology. Some commentators have predicted a diminishing role for histomorphological interpretation in future diagnostics including the classification and predictive testing o...
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Molecular analysis is here to stay in diagnostic histopathology. Some commentators have predicted a diminishing role for histomorphological interpretation in future diagnostics including the classification and predictive testing of neoplasia. A more probable scenario is increasing synergy between morphological and molecular aspects of diagnosis. Analytical techniques applicable to DNA, RNA, and proteins, including important post-translational protein modifications, continue to develop with application to universally available formalin-fixed paraffin-embedded tissues a particularly active area of growth. Successful nanoscale analysis applicable to routinely available materials makes histological microdissection an increasingly attractive tool for diagnostic as well as research practice. Well-engineered laser-assisted microdissection systems allow tissue capture without demanding unrealistic levels of manipulative skill, but even without access to such equipment, non-laser methods can be effective and may not require heavy investment in equipment. Diagnostic histopa-thologists with molecular interests should consider the use of microdissec-tion-based analysis strategies to increase the sensitivity and specificity of molecular analysis in their diagnostic research and clinical practice.
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