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標題: 犬肥大細胞瘤臨床及病理特徵與KIT蛋白表現或c-kit基因突變間之關聯性
Association between clinicopathologic characteristics and KIT expression or c-kit mutation in canine mast cell tumors
作者: 蔡欣亞
Tsai, Hsin-Ya
關鍵字: dogs

出版社: 獸醫學系暨研究所
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摘要: 犬肥大細胞瘤生物特性非常的多樣化,以至於臨床難以評估其預後,目前被認為是一種惡性腫瘤且最終可導致病犬的死亡。犬肥大細胞瘤大部分病程發展快速易轉移至淋巴結,且外科切除後易復發。臨床上,九成以上病犬可藉由細針抽取的方式被診斷出來,但目前卻鮮少文獻有犬肥大細胞瘤細胞學與其預後之間相關性的研究。目前KIT被認為是造成犬肥大細胞瘤的致病因子。本次研究目的主要是建立完整的細胞學與組織學在不同染色上做分級制度來與預後存活期間等做一個完整個評估,藉由了解KIT蛋白位置、KIT表現強度、c-kit基因突變方式與其他臨床病理學因子在犬肥下胞瘤分化及預後方面等是否有其相關性。細胞學以DQ與WG染色,組織學以H&E與Toluidine blue兩種染色;免疫組織化學染色的方式來看KIT 位置與表現強度;另一方面也會抽取腫瘤細胞的RNA經反轉錄酶的作用轉錄成cDNA,再利用PCR技術將c-kit基因片段放大之後定序。研究結果發現細胞學與組織學分級、KIT蛋白位置與其他臨床病理學因子具有顯著相關性且其存活期間具有顯著差異。KIT蛋白位於異常位置時,細胞學與組織學的分級會越高,表腫瘤分化越不良、區域淋巴結及遠端腫瘤轉移率、臨床分期等也會增加,腫瘤團塊大於五公分顯示其預後皆不良。分級越高的腫瘤其c-kit基因點突變的機率也越高,不同的治療方式也會影響其存活時間。根據我們實驗結果,認為細胞學、組織學與KIT表現位置皆可作為犬肥大細胞瘤的獨立預後因子來評估病犬的存活時間。完整的細胞學分級制度希望不只可以提供門診一個快速方便又費用低的診斷方式,也及時提供蓄主病犬的預後狀況。藉由了解KIT蛋白的表現位置與c-kit突變方式希望可以找到一個更有效的方法來治療犬肥大細胞瘤,提高病犬的生活品質。
The biological behavior of canine mast cell tumors (MCTs) is highly variable and often difficult to predict, often have an aggressive behavior that may result in death of the patient. Canine MCTs develop quickly, are rapid to metastasize, and frequently recur after having been removed. Recently, KIT has been implicated in the pathogenesis of canine cutaneous MCTs. The aims of our study were to investigate clinical presentation, establishment of a cytologic grading including the characteristics of Diff-Quik and Wright-Giemsa staining smears patterns observed on fine needle cytology, histological grading in haematoxylin and eosin and toluidine blue stains, KIT in canine MCTs in terms of KIT protein localization and KIT expression levels by immunohistochemical staining and the cDNA of the region encoding c-kit was amplified and sequenced to explore the mutation of c-kit. Results showed that clinicopathologic findings were significantly correlated with KIT immunostaining expression or c-kit mutations in poorly differentiated MCTs. Canine MCTs with aberrant protein localization of KIT, KIT overexpression or deletion mutations of c-kit was positive correlated with the higher histological grade and the decreased survival time. Therefore, clinical staging, regional metastasis, cytopathologic findings and histological grading were important for prognostic prediction in dogs with MCTs. These results might explore the role of KIT in the pathogenesis of higher grade MCTs and provided to predict behavior of canine MCTs for the successful treatment of this neoplastic disease.
其他識別: U0005-2008201015354700
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