scholarly journals Kit Receptor Expression in Canine Cutaneous Mast Cell Tumors (CMCTs) Without C-Kit Mutation

2016 ◽  
Vol 66 (2) ◽  
pp. 222-233
Author(s):  
Ivana Vučićević ◽  
Darko Marinković ◽  
Vladimir Kukolj ◽  
Miloš Vučićević ◽  
Milorad Mirilović ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histopathological Examination ◽  
Polymerase Chain Reaction Amplification ◽  
Histological Grade ◽  
Receptor Expression ◽  
Tissue Samples ◽  
Kit Mutation ◽  
Mast Cell Tumors ◽  
Kit Receptor ◽  
Cutaneous Mast Cell

Abstract Histopathological examination, grading, immunohistochemical staining and molecular genetic examinations are the proposed criteria that should be used for cutaneous mast cell tumors (CMCTs) classification. The presence of aberrant CD117 expression and mutations of the c-kit proto-oncogene could be an indicative parameter for final histological grading. Determination of the connection between the localization of KIT receptor expression and the histological grade of CMCTs without c-kit proto-oncogene mutations was the main goal of this study. The study included twenty four CMCTs and six control skin samples from 30 dogs of different ages, breed and sex. Formalinfixed and paraffin-embedded tissue samples were stained with hematoxylin-eosin and toluidine blue and immunohistochemically tested for CD117 expression. DNA was extracted from the same paraffin blocks and subsequent polymerase chain reaction amplification was performed using PE1 and PE2 primers. Degree of malignancy was determined based on the presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly in 10 high power fields. Based on histological features, fourteen of 24 CMCTs were of a high histological grade, while ten were classified as a lowgrade malignancy. CD117 cytoplasmic expression was observed in nine of fourteen high-grade malignancy CMCTs, which confirms the link between the aberrant CD117 expression and increased cell proliferation.

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.

scholarly journals Prognostic Significance of Kit Receptor Tyrosine Kinase Dysregulations in Feline Cutaneous Mast Cell Tumors

2013 ◽  
Vol 50 (5) ◽  
pp. 797-805 ◽  
Author(s):  
S. Sabattini ◽  
M. Guadagni Frizzon ◽  
F. Gentilini ◽  
M. E. Turba ◽  
O. Capitani ◽  
...  
Keyword(s):  
Mast Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Prognostic Significance ◽  
Mast Cell Tumors ◽  
Kit Receptor ◽  
Cutaneous Mast Cell

scholarly journals Nanog Expression and Proliferation Indices in Canine Cutaneous Mast Cell Tumors

2018 ◽  
Vol 55 (6) ◽  
pp. 849-852
Author(s):  
Julia A. Joselevitch ◽  
Camila N. Barra ◽  
Thiago Henrique M. Vargas ◽  
Lidia H. Pulz ◽  
Adriana T. Nishiya ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histological Grade ◽  
Clinical Information ◽  
Ki67 Index ◽  
Mast Cell Tumors ◽  
Proliferation Indices ◽  
Nanog Expression ◽  
Mast Cell Tumor ◽  
Wide Range ◽  
Cutaneous Mast Cell

Mast cell tumors are one of the most frequent skin tumors in dogs. Treatment decisions often depend on a wide range of clinical information and the main criteria for prognostic formulation are histological grade, mitotic count, Ki67 index, and KIT immunostaining pattern. NANOG is a pluripotency factor expressed by normal and cancer stem cells, which is a prognostic marker and a potential therapeutic target for several human tumors. In the present study, mast cell tumor samples from 41 dogs were evaluated for NANOG and Ki67 by immunohistochemistry. All samples were positive for NANOG but its expression was not correlated with Ki67 index and no significant differences were found with respect to histopathological grades, disease-related mortality, or survival. Our results suggest that, although related to pluripotency, NANOG expression does not correlate with proliferative activity, and is not a reliable prognostic factor for canine cutaneous mast cell tumors.

scholarly journals Morphological Features and KIT Receptor Expression in Canine Cutaneous Mast Cell Tumor and Systemic Mastocytosis / Morfološke Karakteristike I Ekspresija KIT Receptora Kod Kutanih Mastocitoma I Sistemske Mastocitoze Pasa

2015 ◽  
Vol 65 (2) ◽  
pp. 226-237
Author(s):  
Darko Marinković ◽  
Natalija Milčić-Matić ◽  
Milan Jovanović ◽  
Ivana Vučićević ◽  
Slađan Nešić ◽  
...  
Keyword(s):  
Mast Cell ◽  
Systemic Mastocytosis ◽  
Cell Tumor ◽  
Receptor Expression ◽  
Microscopical Examination ◽  
High Grade ◽  
Neoplastic Cells ◽  
Mast Cell Tumor ◽  
Kit Receptor ◽  
Cutaneous Mast Cell

Abstract Mast cell neoplasia in dogs can occur in two different forms: common as cutaneous tumor, or less common as a systemic form of neoplastic mast cell proliferation - systemic mastocytosis. The aim of this study was to compare the histological and cytological features, KIT receptor expression and presence of c-KIT proto-oncogene mutations in neoplastic cells of dogs with canine cutaneous mast cell tumor (CMCT) and systemic mastocytosis. Microscopical examination of the cytological smears obtained from all selected dogs revealed that cellular specimens were constituted mostly of round cells with a central nuclei and fine to coarse purple cytoplasmic granules. Histopathological examination of skin samples of dogs with CMCT and a dog with systemic mastocytosis showed proliferation of the neoplastic mast cells in the superficial and/or deep dermis. Similar findings were observed in tissue samples derived from lymph nodes, spleen, liver, myocardium and kidneys of a dog with systemic mastocytosis. Three dogs with high grade CMCT as well as one dog with systemic mastocytosis showed cytoplasmic CD117 expression, while 3 dogs with low grade CMCT, had membranous expression of CD117. Based on our study, histological features and cytoplasmic CD117 expression in neoplastic cells of dogs with systemic mastocytosis are similar to those in dogs with high grade CMCTs. Nevertheless, mutations of c-KIT proto-oncogene were not found in tumor samples either from dogs with CMCT or dog with systemic mastocytosis.

scholarly journals Expression of KIT Receptor in Feline Cutaneous Mast Cell Tumors

2009 ◽  
Vol 46 (5) ◽  
pp. 878-883 ◽  
Author(s):  
C. Rodríguez-Cariño ◽  
D. Fondevila ◽  
J. Segalés ◽  
R. M. Rabanal
Keyword(s):  
Mast Cell ◽  
Retrospective Study ◽  
Toluidine Blue ◽  
Cellular Location ◽  
Mast Cell Tumors ◽  
Kit Receptor ◽  
Hematoxylin And Eosin ◽  
Cutaneous Mast Cell ◽  
Well Differentiated ◽  
Diffuse Distribution

Twenty-seven feline cutaneous mast cell tumors (MCTs) were selected for this retrospective study. Samples were routinely processed and stained with hematoxylin and eosin (HE) and toluidine blue, and tumors were classified as well-differentiated (19/27), atypical or poorly granulate (7/27), and pleomorphic (1/27). Immunohistochemistry to detect KIT protein was performed on all samples. The immunoreactivity was recorded by distribution within the tumor, cellular location, and intensity. Well-differentiated MCTs were predominantly characterized by diffuse cytoplasmic (8/19) and membranous stain (7/19); a diffuse distribution of KIT positive cells was displayed in most of these tumors as well (15/19). Atypical MCTs showed diffuse distribution of labeled cells (4/7), and diffuse cytoplasm immunostaining was seen most (5/7). The pleomorphic MCT showed diffuse cytoplasmic KIT stain, with moderate labeling intensity, typically displaying focal distribution in deeper areas of the neoplasm. According to the results, there was no correlation between the type of MCTs and KIT expression, although the use of feline KIT immunohistochemistry could be useful to assess the mast cell origin.

scholarly journals HSP32 and HSP90 Immunoexpression, in Relation to Kit Pattern, Grading, and Mitotic Count in Canine Cutaneous Mast Cell Tumors

2016 ◽  
Vol 54 (2) ◽  
pp. 222-225 ◽  
Author(s):  
M. Romanucci ◽  
M. Massimini ◽  
A. Ciccarelli ◽  
D. Malatesta ◽  
L. Bongiovanni ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histological Grade ◽  
Tumor Grade ◽  
Mitotic Count ◽  
Immunohistochemical Expression ◽  
Mast Cell Tumors ◽  
Great Heterogeneity ◽  
Poorly Differentiated ◽  
Cutaneous Mast Cell

Literature data indicate heat shock protein (Hsp) 32 and 90 as potential molecular targets in canine neoplastic mast cells (MCs). However, their immunoexpression patterns in canine mast cell tumors (MCTs) have not been investigated. Thus, the aim of this study was to evaluate the immunohistochemical expression of Hsp32 and Hsp90 in 22 canine cutaneous MCTs, in relation to KIT immunolabeling pattern, histological grade, and mitotic count. All cases showed cytoplasmic labeling of Hsp90, variably associated with nuclear and/or membranous labeling. Relationships of Hsp90 or Hsp32 immunolabeling with KIT pattern, mitotic count, and tumor grade were not observed. However, the reduced Hsp32 immunoexpression observed in most grade III/high-grade MCTs suggests a tendency toward a loss of immunosignal in poorly differentiated MCs. The great heterogeneity in extent and distribution of Hsp90 immunoexpression among the different MCT cases may also partially explain the difficulties in predicting the in vivo biologic activity of Hsp90 inhibitors on canine MCTs.

Internal Tandem Duplication of Exon 8 of c-kit Is Associated With Longer Total Survival in Canine Cutaneous Mast Cell Tumors

2020 ◽  
pp. 030098582097346
Author(s):  
Bouvien A. W. Brocks ◽  
Christof A. Bertram ◽  
Alexander Bartel ◽  
Jolle Kirpensteijn ◽  
Alexandra Collins-Webb ◽  
...  
Keyword(s):  
Mast Cell ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Cellular Proliferation ◽  
Biological Behavior ◽  
Kit Mutation ◽  
Mast Cell Tumors ◽  
Mutational Status ◽  
Cutaneous Mast Cell ◽  
Exon 11

Canine cutaneous mast cell tumors (ccMCTs) have a highly variable biological behavior and accurate prognostication is essential for therapeutic intervention. Internal tandem duplications (ITD) of exon 11 are the most commonly detected c-kit mutation in ccMCTs and are associated with poor prognosis and increased cellular proliferation. The prognostic value of detecting mutations in other exons of c-kit has not been systematically examined. In this study, we analyzed the prognostic value of ITD mutations of exon 8 in c-kit of ccMCTs in comparison to ccMCTs with ITD mutations of exon 11 and ccMCTs without mutations of exon 8 or 11. The mutational status, histological grade, KIT expression pattern, Ki67 index, AgNOR (argyrophilic nucleolar organizing region) score, and Ag67 score were determined in 221 ccMCTs, and outcome was available for 101 dogs. ITD mutations of exon 8 were found in 73/221 (33%), of exon 11 in 100/221 (45%), and none of these mutations in 50/221 (22%) of ccMCTs. None of the dogs with mutations of exon 8 died due to suspected ccMCT-related cause, but 23% dogs with ccMCTs with mutations of exon 11 died due to suspected ccMCT-related cause. Prognostic parameters in ccMCTs with exon 11 mutations were commonly associated with a high proliferative activity and poor prognosis, while prognostic markers in ccMCTs with mutations of exon 8 had lower values similar to those observed in ccMCTs without mutations in exons 8 or 11 of c-kit. This study indicates that screening for ITD mutations in exon 8 in ccMCTs may be helpful to identify less aggressive ccMCTs and may be recommended as a supplementary prognostic test.

scholarly journals Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil

2016 ◽  
Vol 46 (10) ◽  
pp. 1804-1810 ◽  
Author(s):  
Mariana Martins Flores ◽  
Renata Dalcol Mazaro ◽  
Ingeborg Maria Langohr ◽  
Alma Roy ◽  
Keith Strother ◽  
...  
Keyword(s):  
Mast Cell ◽  
Pcr Amplification ◽  
The United States ◽  
Growth Fraction ◽  
Grading System ◽  
Low Grade ◽  
Ki 67 ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Exon 11

ABSTRACT: The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.

scholarly journals Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotransfer on canine mast cell tumors: a histopathologic and immunohistochemical study

2017 ◽  
Vol 51 (3) ◽  
pp. 286-294 ◽  
Author(s):  
Claudia Salvadori ◽  
Tanja Svara ◽  
Guido Rocchigiani ◽  
Francesca Millanta ◽  
Darja Pavlin ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
Cellular Response ◽  
Histopathological Examination ◽  
Combined Treatment ◽  
Gene Electrotransfer ◽  
Neoplastic Cells ◽  
Ki 67 ◽  
Mast Cell Tumors

AbstractBackgroundThe study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT).Materials and methodsEleven dogs with eleven MCTswere included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification.ResultsHistopathological examination of samples at T0confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1and T2neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1and T2and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1and macrophages at T2.ConclusionsThe combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels.

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