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The American Journal of Pathology Jul 2019The past decade has witnessed exponential growth in the generation of high-throughput human data across almost all known dimensions of biological systems. The discipline... (Review)
Review
The past decade has witnessed exponential growth in the generation of high-throughput human data across almost all known dimensions of biological systems. The discipline of network medicine has rapidly evolved in parallel, providing an unbiased, comprehensive biological framework through which to interrogate and integrate systematically these large-scale, multi-omic data to enhance our understanding of disease mechanisms and to design drugs that reflect a deep knowledge of molecular pathobiology. In this review, we discuss the key principles of network medicine and the human disease network and explore the latest applications of network medicine in this multi-omic era. We also highlight the current conceptual and technological challenges, which serve as exciting opportunities by which to improve and expand the network-based applications beyond the artificial boundaries of the current state of human pathobiology.
Topics: Humans; Pathology, Clinical; Pathology, Molecular
PubMed: 31014954
DOI: 10.1016/j.ajpath.2019.03.009 -
Journal of Molecular Biology Jun 2015A tumor is a heterogeneous population of cells that provides an environment in which every cell resides in a microenvironmental niche. Microscopic evaluation of tissue... (Review)
Review
A tumor is a heterogeneous population of cells that provides an environment in which every cell resides in a microenvironmental niche. Microscopic evaluation of tissue sections, based on histology and immunohistochemistry, has been a cornerstone in pathology for decades. However, the dawn of novel technologies to investigate genetic aberrations is currently adopted in routine molecular pathology. We herein describe our view on how recent developments in molecular technologies, focusing on proximity ligation assay and padlock probes, can be applied to merge the two branches of pathology, allowing molecular profiling under histologic observation. We also discuss how the use of image analysis will be pivotal to obtain information at a cellular level and to interpret holistic images of tissue sections. By understanding the cellular communications in the microecology of tumors, we will be at a better position to predict disease progression and response to therapy.
Topics: Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Neoplasms; Pathology, Molecular; Proteomics; Signal Transduction; Tumor Microenvironment
PubMed: 25725260
DOI: 10.1016/j.jmb.2015.02.017 -
Frontiers in Cellular and Infection... 2023
Topics: Pathology, Molecular; Fungi; Basidiomycota; Oomycetes
PubMed: 37886668
DOI: 10.3389/fcimb.2023.1305306 -
Archives of Pathology & Laboratory... Oct 2011
Topics: Gastrointestinal Tract; Humans; Liver; Pancreas; Pathology, Molecular; Pathology, Surgical
PubMed: 21970479
DOI: 10.5858/arpa.2011-0201-ED -
The Journal of Molecular Diagnostics :... Sep 2016Gliomas represent the most common primary intraparenchymal tumors of the central nervous system in adults and children and are a genetic and phenotypic heterogeneous... (Review)
Review
Gliomas represent the most common primary intraparenchymal tumors of the central nervous system in adults and children and are a genetic and phenotypic heterogeneous group. Large multi-institutional studies and The Cancer Genome Atlas have provided firm insights into the basic genetic drivers in gliomas. The main molecular biomarkers routinely applied to evaluate diffuse gliomas include MGMT promoter methylation, EGFR alterations (eg, EGFRvIII), IDH1 or IDH2 mutations, and 1p19q co-deletion. Many of these markers have become standard of care for molecular testing and prerequisites for clinical trial enrollment. Other recent biomarkers include TERT promoter and ATRX mutations, alterations that identify specific molecular subgroups of diffuse gliomas with biological and clinical relevance. It has also become apparent that distinctive patterns of molecular genetic evolution develop in the context of current therapeutic regimens. Important insights have also been uncovered in the field of pediatric glioma, including the identification of recurrent mutation, fusion, and/or duplication events of the BRAF, FGFR1, MYB, and MYBL1 genes in pediatric low-grade gliomas, mutations affecting histone components (H3F3A p.K27M or p.G34) in pediatric high-grade gliomas, and aggressive subsets developing in midline central nervous system structures. Here, we summarize current concepts in molecular testing for glial tumors, including recent findings by large-scale discovery efforts and technologic advances that are affecting routine diagnostic work.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain Neoplasms; Child; Glioma; Humans; Molecular Diagnostic Techniques; Molecular Targeted Therapy; Mutation; Neoplasm Grading; Neoplasms, Second Primary; Pathology, Molecular; Proto-Oncogene Proteins B-raf
PubMed: 27444975
DOI: 10.1016/j.jmoldx.2016.05.005 -
Modern Pathology : An Official Journal... Jan 2017Molecular testing in routine surgical pathology is becoming an important component of the workup of many different types of tumors. In fact, in some organ systems,... (Review)
Review
Molecular testing in routine surgical pathology is becoming an important component of the workup of many different types of tumors. In fact, in some organ systems, guidelines now suggest that the standard of care is to obtain specific molecular panels for tumor classification and/or therapeutic planning. In the head and neck, clinically applicable molecular tests are not as abundant as in other organ systems. Most current head and neck biomarkers are utilized for diagnosis rather than as companion diagnostic tests to predict therapeutic response. As the number of potential molecular biomarker assays increases and cost pressures escalate, the pathologist must be able to navigate the molecular testing pathways. This review explores scenarios in which molecular testing might be beneficial and cost-effective in head and neck pathology.
Topics: Biomarkers; Head and Neck Neoplasms; Humans; Pathology, Molecular; Pathology, Surgical
PubMed: 28060367
DOI: 10.1038/modpathol.2016.192 -
Clinics in Laboratory Medicine Dec 2022
Topics: Humans; Precision Medicine; Pathology, Molecular; Neoplasms
PubMed: 36368791
DOI: 10.1016/j.cll.2022.09.019 -
Virchows Archiv : An International... Feb 2024Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal... (Review)
Review
Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined classifications, while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review highlights some principal molecular alterations in head and neck neoplasms presently available to assist pathologists in the practice of diagnosis, prognostication and prediction of response to treatment.
Topics: Humans; Pathology, Molecular; Head and Neck Neoplasms; Salivary Glands; Immunohistochemistry; Pathologists
PubMed: 38217715
DOI: 10.1007/s00428-023-03731-2 -
The Journal of Pathology. Clinical... May 2021The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological... (Meta-Analysis)
Meta-Analysis
The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology-related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE-GRS (Appraisal of Guidelines for REsearch & Evaluation - Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta-aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full-text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology-related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology-related parameters; (5) transparent reporting of pathology-related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.
Topics: Biomarkers; Biopsy; Clinical Trials as Topic; Humans; Pathology, Clinical; Pathology, Molecular; Practice Guidelines as Topic; Predictive Value of Tests; Research Design; Treatment Outcome
PubMed: 33635586
DOI: 10.1002/cjp2.199 -
Virchows Archiv : An International... Feb 2024Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular... (Review)
Review
Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia. All endocrine gland tumors enjoy a robust correlation between genotype and phenotype. High-throughput molecular analysis demonstrates that endocrine gland tumors can be grouped into molecular groups that are relevant from both pathologic and clinical point of views. In this review, genetic alterations have been discussed and tabulated with respect to their molecular pathogenetic role and clinicopathologic implications, addressing the use of molecular biomarkers for the purpose of diagnosis and prognosis and predicting response to molecular therapy. Hereditary conditions that play a key role in determining predisposition to many types of endocrine tumors are also discussed.
Topics: Humans; Pathology, Molecular; Endocrine Gland Neoplasms; Mutation; Thyroid Gland; Adrenal Gland Neoplasms
PubMed: 38108848
DOI: 10.1007/s00428-023-03713-4