C-kit Gene Product (CD117) Immunoreactivity in Canine and Feline Paraffin Sections

Morini, Maria; Bettini, Giuliano; Preziosi, R.; Mandrioli, Luciana

doi:10.1177/002215540405200515

Cited by 66 publications

(81 citation statements)

References 11 publications

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“…3,26 In dogs, MCTs with aberrant cytoplasmic localization of the KIT receptor tyrosine kinase had a worse prognosis than that of MCTs with a membranous pattern of KIT localization. 17,35 Cytoplasmic expression of KIT has been demonstrated immunohistochemically in feline cutaneous MCTs, 27,33 but its relationship with clinical behavior of the tumor has not been investigated.…”

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Prognostic Value of Histologic and Immunohistochemical Features in Feline Cutaneous Mast Cell Tumors

Sabattini

Bettini

2010

Vet Pathol

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Feline cutaneous mast cell tumors (MCTs) have been histologically classified as mastocytic (well differentiated or pleomorphic) and atypical/poorly granulated. Their biologic behavior ranges from benign to malignant, but prognostic factors are not well defined. Histologic classification, number of tumors, mitotic index, cytoplasmic granularity, and infiltration by eosinophils or lymphocytes were evaluated retrospectively in 25 feline cutaneous MCTs. Immunohistochemistry was applied to assess KIT (CD117) pattern and immunoreactivity score, telomerase expression (human telomerase reverse transcriptase), and proliferation index (MIB-1/Ki67 index). Case outcome was obtained via telephone interviews. The tumors comprised 15 mastocytic well-differentiated, 7 mastocytic pleomorphic, and 3 atypical/poorly granulated MCTs. Immunohistochemically, CD117 was expressed in 13 of 25 tumors (52%), and telomerase reverse transcriptase was expressed in 15 of 22 (68%), with no correlation to histologic classification. Mitotic index, KIT immunoreactivity score, and Ki67 index were significantly higher in mastocytic pleomorphic MCTs than in the other 2 categories. Five cats (20%) died of tumor-related causes. Multiplicity of lesions, pleomorphic phenotype, KIT immunoreactivity score, and mitotic and Ki67-indices correlated with an unfavorable outcome. Mitotic index was the strongest predictive variable. These results suggest that histologic classification, CD117/KIT immunohistochemistry, and proliferation indices may help to identify potentially aggressive cases of feline cutaneous MCT. Aberrant KIT protein localization and telomerase immunoreactivity warrant further exploration as potential prognostic markers.

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Prognostic Value of Histologic and Immunohistochemical Features in Feline Cutaneous Mast Cell Tumors

Sabattini

Bettini

2010

Vet Pathol

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“…35 The c-KIT gene is expressed by many cell types, including mast cells and interstitial cells of Cajal (ICC). 10,27 The normal function of this growth factor receptor has been extensively studied, and it is thought to be associated with growth and differentiation of immature cells. 29,35 KIT protein has been shown to be expressed by neoplastic cells as well; most notably, gastrointestinal stromal tumors (GIST) in people and mast cell tumors (MCT) in dogs.…”

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Immunohistochemical Expression of c-KIT Protein in Feline Soft Tissue Fibrosarcomas

2009

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Abstract. C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P 5 .141, X 2 5 2.166), survivability (P 5 .241, X 2 5 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P 5 .074, X 2 5 3.184).

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“…Em cães, mastócitos normais demonstram o KIT apenas na membrana, enquanto que os mastocitomas indiferenciados tendem a expressar o KIT citoplasmático (London et al 1996, Reguera et al 2000, Morini et al 2004.…”

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Comparação de duas classificações histopatológicas com o padrão de imuno-marcação para KIT, a avaliação da proliferação celular e com a presença de mutações no c-KIT de mastocitomas cutâneos caninos

Carvalho

Nardi

et al. 2017

Pesq. Vet. Bras.

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RESUMO: A graduação histopatológica é o método de eleição para prever o comportamento biológico do mastocitoma e, atualmente, são utilizados os métodos de Patnaik e de Kiupel para dividi-los em graus de malignidade. O objetivo do presente trabalho foi comparar as duas classificações histológicas com as variáveis clínicas, os marcadores imuno-histoquímicos e com a presença de mutações para verificar as características que estão mais relacionadas entre si e com os piores prognósticos. Foram avaliados 61 animais, levando em consideração o sexo, a raça, a idade, a localização tumoral, o grau tumoral pelas classificações de Patnaik e Kiupel, a infiltração de eosinófilos, a marcação do KIT e do Ki-67 e a presença de mutação. As variáveis foram correlacionadas utilizando os testes de qui-quadrado, teste de Fisher, teste de verossimilhança e o teste de risco relativo. Os animais idosos foram os mais acometidos, enquanto os animais sem raça definida e os das raças Boxer, Labrador e Pinscher foram aqueles com maior predisposição ao desenvolvimento tumoral. A localização e a idade estão associadas ao grau tumoral. Os tumores em cabeça, pescoço e região genital têm 10 vezes mais chance de serem classificados como de alto grau (RR=10,667; IC95% 1,909-59,615, p=0,004) e os idosos oito vezes mais chance (RR=8,00; IC95% 0,955-67,009; p=0,029). Os tumores de grau II e os de baixo grau foram os mais encontrados e as duas classificações histológicas demonstram correlação muito significativa entre si (p<0,001). A concentração do infiltrado eosinofílico não demonstrou correlação significativa com nenhuma das classificações histológicas. O padrão KIT foi dependente da localização tumoral (p=0,015), já que os tumores genitais, na cabeça e no pescoço possuíam 18 vezes mais chance de apresentarem padrão citoplasmático (RR=18,571; IC95% 1,954-176,490; p=0,003), e das classificações de Patnaik (p=0,001) e Kiupel (p<0,001), sendo que os tumores de alto grau têm 36 vezes mais chance de apresentarem padrão citoplasmático (RR=36,00, IC95% 4,35-297,948; p<0,001). A marcação do Ki-67 demonstrou dependência da localização (p=0,024). A presença de mutação no exon 11 do domínio justamembrana não demonstrou associação com nenhuma das variáveis clínicas, das classificações histológicas, da concentração de eosinófilos e do padrão KIT. A presença da mutação foi correlacionada significativamente apenas ao Ki-67 (p=0,010). Os resultados obtidos sugerem que a localização é a variável clínica mais relacionada ao prognóstico e que apenas a classificação de Kiupel associada à imuno-histoquímica são eficientes para avaliar o comportamento tumoral.

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C-kit Gene Product (CD117) Immunoreactivity in Canine and Feline Paraffin Sections

Cited by 66 publications

References 11 publications

Prognostic Value of Histologic and Immunohistochemical Features in Feline Cutaneous Mast Cell Tumors

Prognostic Value of Histologic and Immunohistochemical Features in Feline Cutaneous Mast Cell Tumors

Immunohistochemical Expression of c-KIT Protein in Feline Soft Tissue Fibrosarcomas

Comparação de duas classificações histopatológicas com o padrão de imuno-marcação para KIT, a avaliação da proliferação celular e com a presença de mutações no c-KIT de mastocitomas cutâneos caninos

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