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Aging May 2021Immune infiltration is a prognostic marker to clinical outcomes in various solid tumors. However, reports that focus on bone and soft tissue sarcoma are rare. The study...
BACKGROUND
Immune infiltration is a prognostic marker to clinical outcomes in various solid tumors. However, reports that focus on bone and soft tissue sarcoma are rare. The study aimed to analyze and identify how immune components influence prognosis and develop a novel prognostic system for sarcomas.
METHODS
We retrieved the gene expression data from 3 online databases (GEO, TCGA, and TARGET). The immune fraction was estimated using the CIBERSORT algorithm. After that, we re-clustered samples by K-means and constructed immunoscore by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Next, to confirm the prognostic value, nomograms were constructed.
RESULTS
334 samples diagnosed with 8 tumor types (including osteosarcoma) were involved in our analysis. Patients were next re-clustered into three subgroups (OS, SAR1, and SAR2) through immune composition. Survival analysis showed a significant difference between the two soft tissue groups: patients with a higher proportion of CD8+ T cells, macrophages M1, and mast cells had favorable outcomes (p=0.0018). Immunoscore models were successfully established in OS and SAR2 groups consisting of 12 and 9 cell fractions, respectively. We found immunosocre was an independent factor for overall survival time. Patients with higher immunoscore had poor prognosis (p<0.0001). Patients with metastatic lesions scored higher than those counterparts with localized tumors (p<0.05).
CONCLUSIONS
Immune fractions could be a useful tool for the classification and prognosis of bone and soft tissue sarcoma patients. This proposed immunoscore showed a promising impact on survival prediction.
Topics: Adolescent; Adult; Bone Neoplasms; Drug Resistance, Neoplasm; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; Neoplasm Metastasis; Nomograms; Regression Analysis; Sarcoma; Time Factors
PubMed: 33946044
DOI: 10.18632/aging.202956 -
Porcine Health Management Apr 2021The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport...
BACKGROUND
The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport a Escorxadors [SESC] IRTA-CReSA]) from slaughtered pigs from 1998 to 2018 (April) in Catalonia (Spain). The aim of the study was to describe the spectrum of spontaneous neoplastic lesions found in slaughtered pigs and to compare the reported tumor cases with previous published data. Lymphoid neoplasms were characterized and classified using the WHO classification adapted for animals.
RESULTS
The most reported neoplasm during this period was lymphoma (28). Within lymphomas, the B-cell type was the most common, being the diffuse large B-cell lymphoma (15/28) the most represented subtype. Other submitted non-lymphoid neoplasms included melanoma (7), nephroblastoma (3), mast cell tumor (2), liposarcoma (2), osteochondromatosis (2), papillary cystadenocarcinoma (1), peripheral nerve sheath tumor (1), lymphoid leukemia (1), fibropapilloma (1), hemangiosarcoma (1), hepatoma (1), histiocytic sarcoma (1), pheochromocytoma (1) and osteosarcoma (1).
CONCLUSIONS
The existence of a well-established Slaughterhouse Support Network allowed the compilation of comprehensive data for further epidemiological and pathological studies, particularly about less commonly reported lesions in livestock such as neoplasms in pigs.
PubMed: 33827694
DOI: 10.1186/s40813-021-00207-0 -
PLoS Genetics Apr 2021Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological...
Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.
Topics: Animals; Chromosome Mapping; Cyclin-Dependent Kinase Inhibitor p16; Dog Diseases; Dogs; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Hematologic Neoplasms; High-Throughput Nucleotide Sequencing; Histiocytic Sarcoma; Humans
PubMed: 33793571
DOI: 10.1371/journal.pgen.1009395 -
Veterinary Pathology Sep 2021Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple,... (Review)
Review
Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement.
Topics: Animals; Carcinoma, Transitional Cell; Kidney Neoplasms; Neoplasm Grading; Prognosis; Reproducibility of Results; Urinary Bladder Neoplasms
PubMed: 33769136
DOI: 10.1177/0300985821999831 -
Medicine Dec 2020Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC...
INTRODUCTION
Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease is the second most common subtype of systemic mastocytosis. The most common mutation associated with both systemic mastocytosis and myeloid sarcoma is mutation in Kit. Here, we identified the novel KIT D816V and ARID1A G1254S mutations co-occurring in systemic mastocytosis with myeloid sarcoma.
PATIENT CONCERNS
A 33-year old male patient presented multiple skin lesions for 10 years. Symptoms accelerated in 2017 with decreased body weight. Physical examination revealed enlarged lymph nodes in his neck, axilla and inguinal region; conjunctival hemorrhage; gingival hyperplasia. Skin biopsy showed mast cell infiltration. Flow cytometry detected CD2, CD25 and CD117 positive cells in lymph nodes. Codon 816 KIT mutation D816V and codon 1245 ARID1A mutation G1254S were found in peripheral blood. MPO, CD117, CD68 positive cells in lymph nodes indicated co-existing myeloid sarcoma.
DIAGNOSIS
Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease of myeloid sarcoma INTERVENTIONS:: Cytarabine and daunorubicin for myeloid sarcoma and dasatinib for systemic mastocytosis were initiated. Anti-histamine and anti-leukotrienes therapy were used to prevent NSAIDs-induced shock. Platelets were infused to treat bone marrow suppression.
OUTCOMES
Patient was discharged after recovered from bone marrow suppression. Dasatinib continued on outpatient.
CONCLUSION
This is the first case of patient with systemic mastocytosis and myeloid sarcoma simultaneously presenting extensive skin involvements. Mutations of Kit and Arid1a emphasis the importance to notice possibility of various tumors occurring in patients with multiple mutations. In addition, cysteine-leukotrienes-receptor antagonists should always be used to prevent anaphylactic shock due to mast cell activation.
Topics: Adult; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; CD2 Antigens; Cytarabine; DNA-Binding Proteins; Dasatinib; Daunorubicin; Drug Therapy, Combination; Histamine Antagonists; Humans; Interleukin-2 Receptor alpha Subunit; Leukotriene Antagonists; Lymph Nodes; Male; Mastocytosis, Systemic; Mutation; Platelet Transfusion; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Sarcoma, Myeloid; Skin; Transcription Factors; Treatment Outcome
PubMed: 33327223
DOI: 10.1097/MD.0000000000021948 -
Canadian Journal of Veterinary Research... Oct 2020Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful...
Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful in veterinary medicine due to the lack of reliable antibody options, poor tissue preservation, labor-intensive staining, and antigen-retrieval optimization processes. RNAscope hybridization (ISH) is a powerful technology that uses a specific sequence probe to identify targeted mRNA. In this study, we demonstrate RNAscope ISH in 4 common canine malignancies, which are traditionally diagnosed by histopathology and immunohistochemistry. Probes were designed for commonly targeted mRNA markers of neoplastic tumors; these included c-kit in mast cell tumor, microphthalmia-associated transcription factor in malignant melanoma, ionized calcium-binding adapter molecule-1 in histiocytic sarcoma, and alkaline phosphatase in osteosarcoma. A strong staining signal was obtained by these 4 targets in each canine malignancy. These results support the use of RNAscope ISH for definitive diagnosis in canine malignancies.
Topics: Animals; Dog Diseases; Dogs; Immunohistochemistry; In Situ Hybridization; Neoplasms; RNA, Messenger
PubMed: 33012982
DOI: No ID Found -
The Journal of Infectious Diseases Jan 2021It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms...
It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)-infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS.
Topics: Adult; CD4 Lymphocyte Count; Case-Control Studies; Cross-Sectional Studies; Female; HIV Infections; Humans; Immunoglobulin E; Interleukin-33; Male; Sarcoma, Kaposi; Severity of Illness Index; Uganda
PubMed: 32561934
DOI: 10.1093/infdis/jiaa340 -
Genes May 2020The tumor microenvironment plays important roles in cancer biology, but genetic backgrounds of mouse models can complicate interpretation of tumor phenotypes. A deeper...
The tumor microenvironment plays important roles in cancer biology, but genetic backgrounds of mouse models can complicate interpretation of tumor phenotypes. A deeper understanding of strain-dependent influences on the tumor microenvironment of genetically-identical tumors is critical to exploring genotype-phenotype relationships, but these interactions can be difficult to identify using traditional Cre/loxP approaches. Here, we use somatic CRISPR/Cas9 tumorigenesis approaches to determine the impact of mouse background on the biology of genetically-identical malignant peripheral nerve sheath tumors (MPNSTs) in four commonly-used inbred strains. To our knowledge, this is the first study to systematically evaluate the impact of host strain on CRISPR/Cas9-generated mouse models. Our data identify multiple strain-dependent phenotypes, including changes in tumor onset and the immune microenvironment. While BALB/c mice develop MPNSTs earlier than other strains, similar tumor onset is observed in C57BL/6, 129X1 and 129/SvJae mice. Indel pattern analysis demonstrates that indel frequency, type and size are similar across all genetic backgrounds. Gene expression and IHC analysis identify multiple strain-dependent differences in CD4+ T cell infiltration and myeloid cell populations, including M2 macrophages and mast cells. These data highlight important strain-specific phenotypes of genomically-matched MPNSTs that have implications for the design of future studies using similar gene editing approaches.
Topics: Animals; CD4-Positive T-Lymphocytes; CRISPR-Cas Systems; Carcinogenesis; Disease Models, Animal; Gene Editing; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Humans; Mice; Mice, Inbred BALB C; Neurofibrosarcoma; Tumor Microenvironment
PubMed: 32456131
DOI: 10.3390/genes11050583 -
Veterinary Sciences Apr 2020Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical...
Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA (4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation.
PubMed: 32349235
DOI: 10.3390/vetsci7020055 -
British Journal of Haematology May 2020
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Humans; Leukemia, Mast-Cell; Mast-Cell Sarcoma; Middle Aged; Young Adult
PubMed: 32242922
DOI: 10.1111/bjh.16581