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Advances in Anatomic Pathology Nov 2018Although some soft tissue and bone tumors can be identified based on histologic features alone, immunohistochemistry plays a critical diagnostic role for most... (Review)
Review
Although some soft tissue and bone tumors can be identified based on histologic features alone, immunohistochemistry plays a critical diagnostic role for most mesenchymal tumor types. The discovery of recurrent genomic alterations in many benign and malignant mesenchymal neoplasms has added important biologic insights and expanded the spectrum of some diagnostic subgroups. Some tumors are defined by unique genomic alterations, whereas others share abnormalities that are not tumor-specific and can be observed in a sometimes broad range of biologically unrelated neoplasms. We herein focus on novel immunohistochemical markers, based on molecular genetic alterations, which are particularly useful in the diagnostic workup of selected groups of soft tissue and bone tumors, including recently described entities, specifically round cell sarcomas (Ewing sarcoma, CIC-rearranged sarcoma, and BCOR-rearranged sarcoma), vascular tumors (epithelioid hemangioma, epithelioid hemangioendothelioma, and pseudomyogenic hemangioendothelioma), SMARCB1-deficient neoplasms, adipocytic tumors (spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor, and conventional atypical lipomatous tumor), giant cell-rich bone tumors (giant cell tumor of bone and chondroblastoma), and biphenotypic sinonasal sarcoma. Given the complex nature of sarcoma classification, and the rarity of many mesenchymal tumor types, careful integration of clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations is crucial for accurate diagnosis of soft tissue and bone tumors.
Topics: Biomarkers, Tumor; Bone Neoplasms; Humans; Immunohistochemistry; Soft Tissue Neoplasms
PubMed: 30134255
DOI: 10.1097/PAP.0000000000000204 -
Cells Apr 2022Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of... (Review)
Review
Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of cases express the EWS-FLI1 fusion protein that has been shown to function as an aberrant transcription factor driving sarcomagenesis. ES is the second most common malignant bone tumor in children and young adults. Current treatment modalities include dose-intensified chemo- and radiotherapy, as well as surgery. Despite these strategies, patients who present with metastasis or relapse still have dismal prognosis, warranting a better understanding of treatment resistant-disease biology in order to generate better prognostic and therapeutic tools. Since the genomes of ES tumors are relatively quiet and stable, exploring the contributions of epigenetic mechanisms in the initiation and progression of the disease becomes inevitable. The search for novel biomarkers and potential therapeutic targets of cancer metastasis and chemotherapeutic drug resistance is increasingly focusing on long non-coding RNAs (lncRNAs). Recent advances in genome analysis by high throughput sequencing have immensely expanded and advanced our knowledge of lncRNAs. They are non-protein coding RNA species with multiple biological functions that have been shown to be dysregulated in many diseases and are emerging as crucial players in cancer development. Understanding the various roles of lncRNAs in tumorigenesis and metastasis would determine eclectic avenues to establish therapeutic and diagnostic targets. In ES, some lncRNAs have been implicated in cell proliferation, migration and invasion, features that make them suitable as relevant biomarkers and therapeutic targets. In this review, we comprehensively discuss known lncRNAs implicated in ES that could serve as potential biomarkers and therapeutic targets of the disease. Though some current reviews have discussed non-coding RNAs in ES, to our knowledge, this is the first review focusing exclusively on ES-associated lncRNAs.
Topics: Bone Neoplasms; Child; Epigenesis, Genetic; Humans; Neoplasm Recurrence, Local; RNA, Long Noncoding; Sarcoma, Ewing; Young Adult
PubMed: 35455947
DOI: 10.3390/cells11081267 -
International Journal of Molecular... Jan 2018Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous... (Review)
Review
Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients' quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.
Topics: Antineoplastic Agents; Bone Neoplasms; Disease Progression; Humans; Models, Biological; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 29300334
DOI: 10.3390/ijms19010148 -
Molecules (Basel, Switzerland) May 2020Prostate cancer (PCa) is one of the most prevalent and malignant cancer types in men, which causes more than three-hundred thousand cancer death each year. At late stage... (Review)
Review
Prostate cancer (PCa) is one of the most prevalent and malignant cancer types in men, which causes more than three-hundred thousand cancer death each year. At late stage of PCa progression, bone marrow is the most often metastatic site that constitutes almost 70% of metastatic cases of the PCa population. However, the characteristic for the osteo-philic property of PCa is still puzzling. Recent studies reported that the Wnt and Ras signaling pathways are pivotal in bone metastasis and that take parts in different cytological changes, but their crosstalk is not well studied. In this review, we focused on interactions between the Wnt and Ras signaling pathways during each stage of bone metastasis and present the fate of those interactions. This review contributes insights that can guide other researchers by unveiling more details with regard to bone metastasis and might also help in finding potential therapeutic regimens for preventing PCa bone metastasis.
Topics: Bone Neoplasms; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Signal Transduction
PubMed: 32443915
DOI: 10.3390/molecules25102380 -
BMC Cancer Oct 2022The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the...
BACKGROUND
The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the clinicopathological features and prognostic determinants for patients with UMBTs? 2) Can a nomogram be developed for clinicians to predict the short and long-term outcomes for individuals with UMBTs? 3) Does surgery improve outcomes for UMBT patients who received radiotherapy or chemotherapy after balancing the confounding bias?
METHODS
400 UMBT patients were filtrated from the Surveillance, Epidemiology, and End Results database to assess the clinicopathological features, treatments, and factors affecting prognosis. The optimal cutoff values of continuous variables were identified by the x-tile software. Kaplan-Meier method and multivariate Cox proportional hazard modeling were performed to evaluate the independent prognostic factors. Nomogram was further developed by using R software with rms package. The surgical efficacy was further assessed for patients receiving radiotherapy or chemotherapy after performing propensity score matching.
RESULTS
The enrolled cohort included 195 (48.8%) female and 205 (51.2%) male patients. The 2- and 5-year cancer-specific survival (CSS) and overall survival (OS) rate were 58.2 ± 3.0%, 46.8 ± 3.2%, and 46.5 ± 2.6%, 34.4 ± 2.5%, respectively. Nomogram was finally developed for CSS and OS according to the identified independent factors: age, tumor extent, primary tumor surgery, tumor size, and pathology grade. For UMBT patients who received radiotherapy or chemotherapy, surgical intervention was associated with better CSS (pr = 0.003, pc = 0.002) and OS (pr = 0.035, pc = 0.002), respectively.
CONCLUSIONS
Nomogram was developed for individual UMBT patient to predict short and long-term CSS and OS rate, and more external patient cohorts are warranted for validation. Surgery improves outcomes for UMBT patients who received either radiotherapy or chemotherapy.
Topics: Humans; Male; Female; SEER Program; Neoplasm Staging; Prognosis; Nomograms; Bone Neoplasms
PubMed: 36266614
DOI: 10.1186/s12885-022-10153-x -
World Journal of Surgical Oncology Apr 2015The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant... (Review)
Review
The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant cell tumors and chondroblastoma. With the development of modern diagnostic technologies, there appear however many other histological types which raise challenges of diagnosis and treatment. In this article, we review the reported histological types of primary patellar tumors. Specifically, epidemiology, symptomatology, imageology, histopathology, and treatment options for these histological lesions will be discussed, respectively. As there is an increasing focus on the diagnosis and the treatment of these lesions, the availability of the integrated information about primary patellar tumors becomes more significant.
Topics: Bone Neoplasms; Humans; Patella
PubMed: 25906772
DOI: 10.1186/s12957-015-0573-y -
Annals of Palliative Medicine Apr 2019Multiple new options are available in the palliation of bone metastases. Most of these techniques can be used in conjunction with radiation therapy either before or... (Review)
Review
Multiple new options are available in the palliation of bone metastases. Most of these techniques can be used in conjunction with radiation therapy either before or after and are now giving patients who have reached dose limitations new options. These techniques can also be used with vertebroplasty (VP) to increase structural stability post tumor ablation. Localized percutaneous treatment in the bone such as thermal [radiofrequency ablation (RFA)] and light [photodynamic therapy (PDT)] have been used to destroy tumor prior to injection with cement. This educational review will discuss the safety profile, technique and indications for emerging technology in the area of locoregional treatment of bone metastases in conjunction with vertebral augmentation. It will not delve comprehensively into conventional lines of treatment where indications and outcomes have already been well established.
Topics: Bone Neoplasms; Combined Modality Therapy; Humans; Lumbar Vertebrae; Neoplasm Metastasis; Palliative Care; Radiofrequency Ablation; Spinal Neoplasms; Vertebroplasty
PubMed: 30691279
DOI: 10.21037/apm.2018.12.04 -
Neuroendocrinology 2021Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report... (Review)
Review
Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report an incidence of bone metastases as high as 20% in subjects with advanced disease. While the biological mechanisms leading to bone metastatic colonization in NETs have been poorly investigated so far, key steps of osteotropic mechanisms, including the epithelial-to-mesenchymal transition, preparation of the premetastatic niche, migration of circulating tumor cells towards the bone marrow as well as the resulting alterations of the skeletal metabolism, are likely to operate also during the development of NET bone metastases. The skeleton involvement by NETs has a detrimental impact on both quality of life and patients' prognosis, leading to pain in the majority of symptomatic subjects. While it is currently unclear whether or not the earlier recognition of bone involvement by PET/CT imaging techniques employing 68Ga-DOTA-conjugated peptides might improve outcomes through the exploitation of timely treatments, the management of bone-colonizing NETs is today based only on clinical experience from other osteotropic tumors. Here, we summarize the fundamental molecular mechanisms driving bone colonization and revisit both established and novel treatments for patients with bone metastatic NETs.
Topics: Bone Neoplasms; Humans; Neuroendocrine Tumors
PubMed: 32403104
DOI: 10.1159/000508633 -
Molecular Oncology Sep 2018Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis-associated protein 1 (MTA1) is highly overexpressed in metastatic...
Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis-associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of MTA1 knockdown cells. Mechanistic studies revealed that MTA1 silencing led to a significant decrease in the expression of cathepsin B (CTSB), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E-cadherin in both cells and xenograft tumors. Moreover, meta-analysis of clinical samples indicated a positive correlation between MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB-mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer.
Topics: Animals; Antigens, CD; Bone Neoplasms; Cadherins; Cathepsin B; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; Disease Progression; Epithelial-Mesenchymal Transition; Gene Silencing; Heterografts; Histone Deacetylases; Humans; Male; Mice; Mice, Transgenic; Neoplasm Invasiveness; Prostatic Neoplasms; Repressor Proteins; Signal Transduction; Trans-Activators
PubMed: 30027683
DOI: 10.1002/1878-0261.12360 -
Frontiers in Immunology 2024Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high... (Review)
Review
Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.
Topics: Humans; Tumor Microenvironment; Neoplasm Recurrence, Local; Bone and Bones; Bone Neoplasms; Macrophages
PubMed: 38464516
DOI: 10.3389/fimmu.2024.1335366