Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells

2021 ◽  
pp. 030098582110626
Author(s):  
Sanna Hämäläinen ◽  
Lauri Kareinen ◽  
Antti Sukura ◽  
Ilona Kareinen
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Histological Grade ◽  
Normal Tissues ◽  
Mast Cell Tumors ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Specific Protease ◽  
Health And Disease

Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell–specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease.

Reactivity of antibody YU-311 in formalin-fixed, paraffin-embedded specimens of normal organs, non-hematopoietic tumors, and mast cell tumors

1997 ◽  
Vol 47 (8) ◽  
pp. 512-517
Author(s):  
Takeaki Fukuda ◽  
Tomoko Kamishima ◽  
Toshio Kakihara ◽  
Toshiyuki Yamada ◽  
Kazuhito Matsumoto ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cell Tumors ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

scholarly journals DNA purification increases PCR-amplifiable DNA extracted from formalin-fixed, paraffin-embedded canine mast cell tumors for routine KIT mutation detection

2019 ◽  
Vol 31 (5) ◽  
pp. 756-760
Author(s):  
Vanessa S. Tamlin ◽  
Elizabeth C. Dobson ◽  
Lucy Woolford ◽  
Anne E. Peaston
Keyword(s):  
Mast Cell ◽  
Dna Extraction ◽  
Mutation Detection ◽  
Pcr Amplification ◽  
Low Grade ◽  
Kit Mutation ◽  
Mast Cell Tumors ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

DNA amplification by PCR detects KIT exon 11 internal tandem duplications in canine mast cell tumors (MCTs). Tissue-specific inhibitors often contaminate DNA extracted from formalin-fixed, paraffin-embedded (FFPE) canine MCTs, blocking PCR amplification and, consequently, preventing mutation detection. We used a commercial kit to extract DNA from FFPE canine MCTs. Two independent PCR assays, each with one primer set, were used to amplify target genes ( HPRT and KIT) directly after FFPE DNA extraction. PCR amplification failed with at least one primer set in 153 of 280 samples (54.6%, 95% CI: 48.8–60.5%). One or 2 DNA washing steps were required to remove PCR inhibitors in 130 of 280 (46.4%) and 23 of 280 (8.2%) of these cases, respectively. DNA concentration and quality (A260/A280 and A260/A230) either pre- or post-washing were not associated with ability of the samples to be amplified by PCR using both HPRT and KIT primer sets. Low-grade and subcutaneous MCTs were less likely to amplify directly after DNA extraction and without any washing steps compared to high-grade MCTs using KIT gene primers.

scholarly journals Stereology in Grading and Prognosis of Canine Cutaneous Mast Cell Tumors

2021 ◽  
pp. 030098582098513
Author(s):  
Mafalda Casanova ◽  
Sandra Branco ◽  
Inês Berenguer Veiga ◽  
André Barros ◽  
Pedro Faísca
Keyword(s):  
Mast Cell ◽  
Clinical Outcome ◽  
Prognostic Value ◽  
Histological Grade ◽  
Intraobserver Variability ◽  
Low Grade ◽  
High Grade ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Grade Iii

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]<125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.

Canine Extracutaneous Mast-cell Tumours Consisting of Connective Tissue Mast Cells

2000 ◽  
Vol 123 (4) ◽  
pp. 306-310 ◽  
Author(s):  
N. Iwata ◽  
K. Ochiai ◽  
T. Kadosawa ◽  
M. Takiguchi ◽  
T. Umemura
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

scholarly journals Systemic mastocytosis with subcutaneous hemorrhage and edema in a Greyhound dog: case report and review of diagnostic criteria

2020 ◽  
Vol 33 (1) ◽  
pp. 95-100
Author(s):  
Alexander Aceino ◽  
Unity Jeffery ◽  
Julie Piccione ◽  
Carolyn L. Hodo
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Diagnostic Criteria ◽  
Complete Blood Count ◽  
Systemic Mastocytosis ◽  
Mast Cell Tumors ◽  
Multiple Organs ◽  
Subcutaneous Edema ◽  
Diagnostic Framework ◽  
Criteria For Diagnosis

Systemic mastocytosis, characterized by infiltration of multiple organs by neoplastic mast cells, is a well-described entity in human medicine with specific criteria for diagnosis, but is ill defined in veterinary literature. Hemostatic disorders are reported in humans affected by systemic mastocytosis but have not been well described in veterinary literature. A 5-y-old, spayed female Greyhound dog had a 1-mo history of progressive ventral cutaneous edema, hemorrhage, and pain. Cytology of an antemortem aspirate from the subcutis of the ventral abdomen was suggestive of mast cell neoplasia, but no discrete mass was present. The dog was euthanized and submitted for autopsy; marked subcutaneous edema and hemorrhage were confirmed. The ventral abdominal panniculus and dermis superficial to the panniculus carnosus were infiltrated by a dense sheet of neoplastic mast cells. The neoplastic cells contained toluidine blue–positive granules and formed aggregates within the bone marrow and several visceral organs, including the liver, spleen, heart, and kidney. Diffuse edema and hemorrhage is an unusual presentation of mast cell tumors in dogs. Antemortem tests, including complete blood count, coagulation profile, and viscoelastic coagulation testing, were suggestive of a primary hemostatic defect. We discuss here the diagnostic criteria used in humans, how these can be applied to veterinary patients, and the limitations of the current diagnostic framework.

scholarly journals Specificity and sensitivity of immunohistochemical detection of factor VIII/von Willebrand factor antigen in formalin-fixed paraffin-embedded tissue.

1982 ◽  
Vol 30 (4) ◽  
pp. 371-377 ◽  
Author(s):  
R D McComb ◽  
T R Jones ◽  
S V Pizzo ◽  
D D Bigner
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Immunohistochemical Detection ◽  
Normal Tissues ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Formalin Fixed

The immunohistochemical detection of factor VIII/von Willebrand factor antigen (FVIII/vWF-AG) in formalin-fixed paraffin-embedded tissues was investigated using the peroxidase-antiperoxidase (PAP) method. Highly purified human FVIII/vWF was used to raise rabbit anti-FVIII/vWF-AG serum. In addition to anti-FVIII/vWF-AG activity, the unabsorbed antiserum had anti-IgG, anti-IgM, and anti-alpha2-macroglobulin specificities. Following exhaustive absorption with these proteins, the antiserum reacted monospecifically for FVIII/vWF-AG in immunodiffusion, immunoelectrophoresis, and PAP immunohistochemistry. Sections of normal tissues from six patients and a total of 43 neoplasms were examined. Treatment of the tissue sections with trypsin prior to application of the antiserum markedly increased the sensitivity of FVIII/vWF-AG detection. The positive staining for FVIII/vWF-AG was restricted to endothelial cells in both neoplastic and nonneoplastic tissue. In general, the hyperplastic endothelia in neoplastic and reactive tissues stained more intensely than those in normal tissues. Expression of FVIII/vWF-AG by nonendothelial neoplastic cells was not observed. FVIII/vWF-AG is a reliable marker for endothelial cells.

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