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Neoplasia
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Molecular pathology (or molecular diagnostics) involves testing tumour-derived nucleic acids or proteins for single or multiple genetic or molecular changes that can be used to inform management or treatment decisions. A common example is testing breast cancers for either HER2 amplification (by fluorescence in-situ hybridization on tumour tissue sections) and/or HER2 protein overexpression (by immunohistochemistry), to advise use of the monoclonal antibody therapy Trastuzumab (Herceptin), an antibody that binds and blocks HER2 protein function, and this is effective in HER2+ breast cancers. In chronic myeloid leukaemia, detection of the Philadelphia chromosome translocation, t(9;22), a reciprocal chromosome translocation that fuses together parts of the BCR gene on chromosome 9 with the ABL gene on chromosome 22, to generate a chimaeric BCR–ABL protein with a deregulated tyrosine kinase activity in leukaemic cells. If detected, this permits treatment with Imatinib (Glivec) a small molecule inhibitor of the tyrosine kinase enzymic activity of the BCR–ABL protein. Common molecular pathology tests used on tumours are listed in Table 6.16.
Head and Neck Pathology
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Ram Moorthy, Adrian T. Warfield, Max Robinson
For neoplastic disease, the pathologist has a significant role in assessing whether the tumour has been completely eradicated. For malignant disease, parameters such as tumour grade and stage are important prognostic indicators and determine adjuvant treatment. Furthermore, the evolution of molecular pathology in recent years has led to the emergence of tests that can be used to tailor treatment for individual patients. Biological treatments, such as trastuzumab for breast cancer, require ‘companion diagnostic tests’ to select the right patients. This strategy ensures that patients have access to the most effective treatment and the best chance of cure. Whilst targeted treatments for head and neck disease remain elusive, this is likely to change over the next decade.
Tissue and Molecular Diagnosis
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
The broad heading of diagnostic molecular pathology refers to multiple tests that assess molecules (proteins, ribonucleic acid [RNA] and deoxyribonucleic acid [DNA]) in tissue. The information that they provide may be useful for diagnosis, prognostic predictions, identifying patients with a hereditary cancer risk, determining treatment and identifying residual disease after treatment. Immunohistochemistry is conventionally excluded from this category.
Site-agnostic biomarker-guided oncology drug development
Published in Expert Review of Molecular Diagnostics, 2020
For decades, cancers have been classified according to the organ from where the tumor arises. The thinking behind this classification was that the origin of the tumor was closely linked to the biological behavior and hence this characteristic could be used to guide the selection of an optimal therapy [1]. However, in most cases, this shown not to be the case and the past decades have taught us that cancer is a group of very heterogeneous diseases where complex molecular mechanisms play a key role. The development within molecular diagnostics has enabled us to study these mechanisms and have fostered a greater understanding of the molecular pathology and what drives the diseases. This increased molecular understanding has slowly changed the way that cancers are classified and the way that anticancer drugs are developed. Many cancer diseases can now be divided into subgroups based on molecular characteristics, and an increasing number of drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these biomarker assays support the development process they are also an important treatment decision tool in relation to the use of the drugs after regulatory approval. When such a predictive assay is linked to a specific drug it is called a companion diagnostic (CDx) [2].
ESR1 mutations: a new biomarker in breast cancer
Published in Expert Review of Molecular Diagnostics, 2019
Marcela Carausu, François-Clément Bidard, Celine Callens, Samia Melaabi, Emmanuelle Jeannot, Jean-Yves Pierga, Luc Cabel
Recent advances in molecular pathology have opened the gates to a new era of precision medicine – based practices in all fields of oncology. The treatment algorithm of breast cancer hormone-receptor (HR+) has a particular history in this matter, with its targeted endocrine therapy. As all other targeted therapies, the downside is the development of resistance to this therapy. Considering the high prevalence of HR+ breast cancer in the general population, the mechanisms of resistance to endocrine therapy represent an area of interest in breast cancer research and are being deciphered with the help of the new technologies of molecular and genetic diagnosis. One important mechanism is the genetic alteration of ESR1 gene, especially gain-of-function point mutations in the LBD domain, conferring ligand-independent constitutive activation of ER.
Benign ependymoma with extensive intracranial and spinal cerebrospinal fluid dissemination: case report and literature review
Published in British Journal of Neurosurgery, 2019
Fangmei Zhu, Jurong Ding, Yumei Li, Dewang Mao, Xianglei He, Wanyuan Chen, Lin Lou, Zhongxiang Ding
Currently, the trend in glioma classification has favored molecular diagnosis. Molecular pathology is playing an increasingly important role in daily practice to meet the needs of individualized diagnosis and treatment guidance. As a consequence of chromosomal translocation, LOH 1p/19q status implies that the pathological classification should be that of oligodendroglioma, which is characterized by a prolonged survival time and sensitivity to chemoradiotherapy.21 Mutation of the IDH1 or IDH2 gene is mostly observed in a low-grade glioma or a secondary high-grade glioma that develops from a lower-grade glioma. An IDH-mutated tumor tends to have a better prognosis than the same non-mutated subtype. Conjointly analyzing TERT and the mutation of IDH in glioma subtypes contributes to glioma classification and prognosis.22 In our case, the results of molecular pathology are negative, which suggest that this case is not a oligodendroglioma and that the patient may not have benefitted from chemotherapy with an alkylating agent such as temozolomide.