Chordomas: A review with emphasis on their pathophysiology, pathology, molecular biology, and genetics

Karpathiou, Georgia; Dumollard, Jean Marc; Dridi, Maroa; Col, Pierre Dal; Barral, Fabrice-Guy; Boutonnât, Jean; Péoc’h, Michel

doi:10.1016/j.prp.2020.153089

Cited by 26 publications

(37 citation statements)

References 52 publications

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“…Chordomas are rare bone tumors, accounting for 1.4% of primary bone malignancies and showing a median overall survival of 7 years; they are assumed to derive from notochordal remnants probably driven by brachyury activation [ 1 ]. These malignant tumors, primarily treated with surgery and/or radiotherapy, are notably resistant to chemotherapy [ 2 ]. The reason for their chemoresistance is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, lysosomes, that receive extracellular/cell surface molecules by endocytosis and intracellular components by autophagy, are important in drug resistance as they isolate chemotherapeutic drugs [ 6 ]. The principal morphologic feature of chordomas, already described by Virchow, is their cytoplasmic vacuoles, accounting for their bubbled cytoplasm and explaining the description Virchow gave to chordoma cells: “physaliphorous” (from the Greek words physalis = bubble and phorous = bearing) [ 2 ]. The exact nature of these vacuoles remains unknown, but they are considered lysosome-related organelles [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The exact nature of these vacuoles remains unknown, but they are considered lysosome-related organelles [ 7 ]. Furthermore, brachyury, the main gene implicated in chordomas pathology [ 2 ], has been shown to induce autophagy in glioblastoma cell lines [ 8 ]. Despite this indirect evidence of chordomas association with autophagy, to the best of our knowledge, the presence of this mechanism has never been studied in chordoma tissues.…”

Section: Introductionmentioning

confidence: 99%

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Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

Karpathiou

Dridi

Krebs-Drouot

et al. 2021

Cancers

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Chordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords (n = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

Karpathiou

Dridi

Krebs-Drouot

et al. 2021

Cancers

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“…Development of neurologic deficits and newonset seizures are commonly followed by neurologic workup that includes magnetic resonance imaging (MRI). Computer tomography (CT) with contrast enhancement is less sensitive in detecting the typical features of glioblastoma [58].…”

Section: Diagnosismentioning

confidence: 99%

An Overview of Brain Tumor

Pichaivel¹,

Anbumani²,

Panneerselvam³

et al. 2022

Brain Tumors

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Brain tumor is an abnormal growth of mass of cells in (or) around the brain. Brain tumors can be malignant (cancerous) or being non-cancerous. It is the most common malignant primary intracranial tumors of central nervous system. Brain tumor can affect brain function if they grow large enough to press on surrounding nerves, blood vessels and tissues. Only one third of tumors formed in the brain are formed as cancerous cells. Brain tumors release molecular information to the circulation. Liquid biopsies collect and analyse tumor component in the body fluid and there is an increasing interest in investigation of liquid biopsies as substitute from tumor markers. Tumor-derived biomarkers include nucleic acids, proteins and tumor-derived extracellular vesicles that accumulate in blood (or) cerebrospinal fluid. Circulating biomarkers like O-6-methylguanine DNA methyl transferase, epidermal growth factor, isocitrate dehydrogenase, circulating tumor cells, circulating cell free micro RNAs, circulating extracellular vesicles plays and important role in causing a cancer. Brain tumor can be treated by surgery, radiation therapy (or) targeted therapy. Radiation therapy is often given afterwards. As a consequence, the most recent review reviewed the present state of research with the hopes of discovering a new brain tumor inhibitor that may be used to treat advanced malignancies.

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“…Chordomas-a rare subtype of sarcoma of notochordal origin, which arise either in the skull base, the spine, or in the sacrum [80]-are, potentially the most immunologically "hot" sarcoma type. This is exemplified by their frequent infiltration with considerable amounts of CD4+ and CD8+ T cells, as well as with M1-like and M2-like TAMs [39][40][41][42].…”

Section: The Tumor Microenvironment In Sarcomas With Complex Genomesmentioning

confidence: 99%

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

et al. 2021

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Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas.

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Chordomas: A review with emphasis on their pathophysiology, pathology, molecular biology, and genetics

Cited by 26 publications

References 52 publications

Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

An Overview of Brain Tumor

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

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