Detection of IDH mutations in cerebrospinal fluid: A discussion of liquid biopsy in neuropathology
Published on: 17th September, 2020
OCLC Number/Unique Identifier: 8873201615
Isocitrate dehydrogenase (IDH) mutations are a common event in secondary glioblastoma multiforme and lower-grade adult infiltrative astrocytomas and independently confer a better prognosis [1,2]. These are highly conserved mutations during glioma progression and thus also a useful diagnostic marker amenable to modern molecular sequencing methods. These mutations can even be detected in sites distant from the primary tumour. We use an illustrative case of a patient with radiologically suspected recurrent astrocytoma and negative histology, but positive IDH-mutated tumour DNA detected within CSF. Our results demonstrated the usefulness of liquid biopsy for recurrent glioma within the context of equivocal or negative histopathological results, whilst also showing the ability to detect a de-novo IDH-2 mutation not present in the previous resection. Building on this ‘proof-of-concept’ result, we also take the opportunity to briefly review the current literature describing the various liquid biopsy substrates available to diagnose infiltrative gliomas, namely the study of circulating tumour DNA, circulating tumour cells, and extracellular vesicles. We outline the current challenges and prospects of liquid biopsies in these tumours and suggest that more studies are required to overcome these challenges and harness the potential benefits of liquid biopsies in guiding our management of gliomas
Flow cytometry potential applications in characterizing solid tumors main phenotype, heterogeneity and circulating cells
Published on: 24th August, 2021
OCLC Number/Unique Identifier: 9213084224
Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness
New insights of liquid biopsy in ovarian cancer
Published on: 29th September, 2022
Through the development of new analysis technologies, many issues regarding the approach to tumoral diseases have been elucidated. With analytical assays developed in the last years, various omics technologies have evolved in such a manner that the characteristics of tumor cells and products can be evaluated (assessed) in the bloodstream of cancer patients at different times. Ovarian Cancer (OC) is one of the most difficult to diagnose umors, with low survival rates due to the high heterogeneity of these diseases that are distinct in terms of etiology and molecular characteristics, but which simply share an anatomical appearance. Recent findings have indicated that several types of ovarian cancer classified into different histotypes are in fact derived from non-ovarian issues and share few molecular similarities. Within this context, ovarian cancer screening and diagnosis can be made through the evaluation of circulating tumor cells in peripheral blood using liquid biopsy technologies. Advances in the study of various molecules analyzed by liquid biopsy have shown that elucidation of intratumoural and intertumoural heterogeneity and spatial and temporal tumor evolution could be traced by serial blood tests rather than by histopathological analyses of tissue samples from a primary tumor. Therefore, evaluation of some molecules such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating cell-free RNA (non-coding and mRNA, extracellular vesicles), tumor-educated platelets or different miRNAs using liquid biopsy could lead to improvement of patient management.
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