scholarly journals c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine

2017 ◽  
Vol 32 (1) ◽  
pp. 394-405 ◽  
Author(s):  
K.M. Weishaar ◽  
E.J. Ehrhart ◽  
A.C. Avery ◽  
J.B. Charles ◽  
R.E. Elmslie ◽  
...  
Keyword(s):  
Mast Cell ◽  
Kit Mutation ◽  
Mast Cell Tumors ◽  
Response Predictors

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 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.

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.

Immunohistochemical Expression of Vascular Endothelial Growth Factor as a Prognostic Marker for Canine Mast Cell Tumors

2021 ◽  
Vol 42 ◽  
pp. 100506
Author(s):  
Samanta Rios Melo ◽  
Eric Vieira Januário ◽  
Erika Zanuto ◽  
Bruna de Castro Miranda ◽  
Thais Rodrigues Macedo ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Mast Cell ◽  
Growth Factor ◽  
Prognostic Marker ◽  
Vascular Endothelial ◽  
Immunohistochemical Expression ◽  
Mast Cell Tumors ◽  
Endothelial Growth Factor

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.

Correlation of histologic grading of canine mast cell tumors with Ki67/PCNA/AgNOR/c-Kit scores: 38 cases (2002-2003)

2004 ◽  
Vol 2 (2) ◽  
pp. 98-98 ◽  
Author(s):  
P. J. Bergman ◽  
D. M. Craft ◽  
S. J. Newman ◽  
K. Baer ◽  
M. A. Camps-Palau ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histologic Grading ◽  
Mast Cell Tumors

scholarly journals Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Magalie Joris ◽  
Sophie Georgin-Lavialle ◽  
Marie-Olivia Chandesris ◽  
Ludovic Lhermitte ◽  
Jean-François Claisse ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Leukaemia ◽  
Therapeutic Approaches ◽  
Kit Mutation ◽  
Short Survival Time ◽  
Therapeutic Choice ◽  
Molecular Abnormality ◽  
Mast Cell Leukemia ◽  
Genotypic Characteristics ◽  
Diagnostic Investigations

Mast cell leukemia (MCL) is a rare and aggressive disease with poor prognosis and short survival time. D816V c-KIT mutation is the most frequent molecular abnormality and plays a crucial role in the pathogenesis and development of the disease. Thus, comprehensive diagnostic investigations and molecular studies should be carefully carried out to facilitate the therapeutic choice. A MCL patient’s case with rare phenotypic and genotypic characteristics is described with review of major clinical biological and therapeutic approaches in MCL.

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