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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 -
Virchows Archiv : An International... Jan 2017The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid,... (Review)
Review
Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.
The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.
Topics: Expert Testimony; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Pathology, Molecular
PubMed: 27678269
DOI: 10.1007/s00428-016-2025-7 -
Harefuah Jun 2013Recent advances in understanding the molecular basis of cancer have led to the development of novel targeted therapies. The advantage of these therapies lies in their... (Review)
Review
Recent advances in understanding the molecular basis of cancer have led to the development of novel targeted therapies. The advantage of these therapies lies in their increased efficiency and reduced adverse events as compared to classicaL chemotherapy. One of these novel treatments is antibodies directed against Epidermal Growth Factor Receptor for colorectal carcinoma (CRC). Apparently, this treatment is only effective in patients whose tumor carries a wild-type copy of KRAS. Therefore, treatment decision in patients with CRC is based on molecular pathoLogical examination of the tumor tissue. Molecular testing for KRAS mutation in CRC carries new challenges. As opposed to germ-line mutations, which are present in all the cells, most of the mutations in cancer are somatic and present only in the tumor cells. This might make the diagnosis more difficult since the tumor tissue contains the tumor cells as well as stromal and inflammatory cells. Choosing an area that contains a smaller fraction of tumor cells might Lead to false negative results in the moLecular diagnosis. Identification of a tumor-rich area by a pathologist, who also determines the tumor cell fraction and chooses a test modality with the required sensitivity, will reduce the risk for such mistakes. Another issue that requires attention is intra-tumor heterogeneity. Recent reports have demonstrated that tumor cell population contains several sub-groups with differences in their mutational status. This phenomenon might affect the treatment choice and patients' response to therapy. However, recent reports in the literature indicate relative homogeneity for KRAS mutational status in CRC. In summary, molecular pathology is a new and rapidly evolving field chaLLenging pathologists involved in cancer diagnosis. It is crucial to make sure that the testing would be carried out in specialized centers that can address the molecular, as well as the histo-pathological aspects of the disease, to allow accurate diagnoses of high quality.
Topics: Colorectal Neoplasms; Humans; Molecular Targeted Therapy; Mutation; Pathology, Molecular; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins
PubMed: 23885470
DOI: No ID Found -
Annals of Oncology : Official Journal... Aug 2013Molecular testing of tumor samples to guide treatment decisions is of increasing importance. Several drugs have been approved for treatment of molecularly defined... (Review)
Review
Molecular testing of tumor samples to guide treatment decisions is of increasing importance. Several drugs have been approved for treatment of molecularly defined subgroups of patients, and the number of agents requiring companion diagnostics for their prescription is expected to rapidly increase. The results of such testing directly influence the management of individual patients, with both false-negative and false-positive results being harmful for patients. In this respect, external quality assurance (EQA) programs are essential to guarantee optimal quality of testing. There are several EQA schemes available in Europe, but they vary in scope, size and execution. During a conference held in early 2012, medical oncologists, pathologists, geneticists, molecular biologists, EQA providers and representatives from pharmaceutical industries developed a guideline to harmonize the standards applied by EQA schemes in molecular pathology. The guideline comprises recommendations on the organization of an EQA scheme, defining the criteria for reference laboratories, requirements for EQA test samples and the number of samples that are needed for an EQA scheme. Furthermore, a scoring system is proposed and consequences of poor performance are formulated. Lastly, the contents of an EQA report, communication of the EQA results, EQA databases and participant manual are given.
Topics: Biomarkers, Tumor; Drug Prescriptions; Europe; Humans; Molecular Targeted Therapy; Neoplasms; Pathology, Molecular; Quality Assurance, Health Care
PubMed: 23613479
DOI: 10.1093/annonc/mdt153 -
Therapeutische Umschau. Revue... 2019Pathology of infectious diseases The pathology of infectious diseases is an exciting interdisciplinary field, despite its niche existence that is somewhat overshadowed... (Review)
Review
Pathology of infectious diseases The pathology of infectious diseases is an exciting interdisciplinary field, despite its niche existence that is somewhat overshadowed by tumor diagnostics. However, the strength of pathology lies in the correlation of the inflammatory patterns and pathogen detection. Moreover, corresponding tissue investigations often allow a rapid diagnosis of the disease, and additional investigations, such as immunohistochemistry or molecular pathology, enable a rapid pathogen characterization with a high sensitivity and specificity. In addition, the molecular analysis allows the detection of pathogens that are difficult, dangerous or not at all to breed. It can be assumed that complex infectious diseases will increase due to iatrogenic interventions, migration, antibiotic resistance and climate change, and that pathology, in close cooperation with its treating colleagues, will increasingly play an important role in the care of patients.
Topics: Communicable Diseases; Humans; Pathology, Molecular
PubMed: 31913100
DOI: 10.1024/0040-5930/a001120 -
Seminars in Diagnostic Pathology Sep 2019Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis,... (Review)
Review
Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis, tumorigenesis, and immune function contribute to the development of these assays. However, each technique, if applied incorrectly or in ignorance, can lead to difficulties in execution or errors in interpretation. In this review of commonly used molecular diagnostic tests, including immunohistochemistry, microsatellite instability testing, chromosomal microarray testing, and conventional and next-generation sequencing, the emphasis will be on potential pitfalls and considerations for each platform. Emerging technologies that may be used in clinical applications in the near future will also be discussed. An understanding of the methodologies, advantages, and drawbacks of molecular assays will help pathologists aid in diagnostic and therapeutic decisions.
Topics: Humans; Molecular Diagnostic Techniques; Pathology, Molecular
PubMed: 31182318
DOI: 10.1053/j.semdp.2019.06.002 -
Pathologie (Heidelberg, Germany) Mar 2023
Topics: Humans; Pathology, Molecular; Proto-Oncogene Proteins c-ret; Neoplasms
PubMed: 36484806
DOI: 10.1007/s00292-022-01168-z -
Pathologie (Heidelberg, Germany) Dec 2023The situation regarding digital pathology in Austria is manageable compared to other countries. Active Austrian examples are the consortium EMPAIA, the private-public... (Review)
Review
The situation regarding digital pathology in Austria is manageable compared to other countries. Active Austrian examples are the consortium EMPAIA, the private-public partnership Bigpicture, the Austrian Society for Clinical Pathology and Molecular Pathology (OEGPath), the company TissueGnostics, and the Austrian Platform for Personalized Medicine (OEPPM).
Topics: Austria; Telepathology; Pathology, Clinical; Pathology, Molecular; Precision Medicine
PubMed: 37987811
DOI: 10.1007/s00292-023-01278-2 -
The Journal of Molecular Diagnostics :... Mar 2016Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to...
Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology.
Topics: Clinical Laboratory Techniques; Curriculum; Education, Medical, Graduate; Genomics; Humans; Infections; Internship and Residency; Neoplasms; Pathology, Molecular; Pharmacogenetics
PubMed: 26857063
DOI: 10.1016/j.jmoldx.2015.10.006 -
Clinics in Laboratory Medicine Dec 2013
Topics: Genomics; Humans; Pathology, Molecular; Precision Medicine
PubMed: 24267196
DOI: 10.1016/j.cll.2013.09.003