Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93041
標題: Association between expressions of KIT with PI3K/AKT/mTOR signal transduction pathway and clinicopathological factors in canine cutaneous mast cell tumors
犬皮膚型肥大細胞瘤之KIT和PI3K/Akt/mTOR訊息傳遞路徑中蛋白表現與臨床病理因子間之關聯性
作者: Cho-Hau Yang
楊筑皓
關鍵字: KIT蛋白
磷酸化絲氨酸激?
免疫組織化學染色
肥大細胞瘤

KIT
p-Akt
immunohistochemical staining
MCT
canine
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摘要: 犬體表型肥大細胞瘤為犬體表最常見之腫瘤。本實驗是利用免疫組織化學染色和免疫活性評分系統探討KIT/PI3K/Akt/mTOR訊息傳遞路徑在50個犬體表型肥大細胞瘤中的表現及活化情形,並進一步研究上述路徑中的蛋白與臨床病理因子之間的關係。在KIT的免疫組織化學染色中可發現,KIT有三種不同的分佈型態,分別為 (一) 只分佈在細胞膜、(二) 細胞質呈團聚集分佈和(三) 細胞質瀰漫性分佈,且此分佈型態與犬體表型肥大細胞瘤的組織學分級有顯著相關 (P = 0.004)。絕大多數組織學分級較低的腫瘤,其KIT分佈多屬於第二型;反之,在組織學分級較高的腫瘤,其KIT分佈多屬於第三型。當KIT分佈為第二型(92.6%, 25/27)或第三型(100%, 13/13) 時,癌化肥大細胞中的Akt會過度表現。在p-Akt的免疫組織化學染色中也可發現三種不同分佈型態,分別為 (一) 只分佈在細胞質、(二) 細胞質呈現較濃染,但細胞核呈現較稀疏染色和 (三) 細胞質與細胞核皆呈現陽性反應,但細胞核較濃染。腫瘤細胞內p-Akt的分佈,與KIT的分佈型態有顯著相關(P = 0.005),當KIT蛋白分佈為第一型時,p-Akt主要瀰漫分佈於細胞質(70.0%, 7/10);當KIT蛋白分佈為第三型時,p-Akt主要瀰漫分佈於細胞質及細胞核為主(61.5%, 8/13)。此外,本實驗發現p-Akt不同的分佈型態,與肥大細胞瘤的轉移有顯著的相關(P = 0.001)。在沒有發生轉移的肥大細胞瘤組織中可見多數的p-Akt只分佈在細胞質(51.7%, 15/27),而在有轉移的肥大細胞瘤組織中則見多數的p-Akt除了分佈在細胞質,也分佈在細胞核內且其表現較濃染(57.1%, 12/21)。當p-Akt活性增強時,下游的mTOR蛋白也會過度表現,而p-mTOR的活性也會隨之增加。實驗成果推測KIT/PI3K/Akt/mTOR訊息傳遞路徑在犬體表型肥大細胞瘤中扮演著重要角色,而p-Akt的分佈型態,可作為評估肥大細胞瘤患犬是否發生轉移的重要指標。
Mast cell tumors (MCTs) are one of the most common cutaneous tumors in the dog. This study aimed to evaluate KIT, PI3K, Akt, p-Akt, mTOR and p-mTOR expression in 50 canine cutaneous MCTs and investigate the correlations between the proteins mentioned above and clinicopathologic parameters by the immunohistochemical staining and immunoreactive score system. There were three KIT immunostaining patterns that are pattern I: primarily along the cytoplasmic membrane, pattern II: the intense, focally clustered cytoplasmic KIT staining, and pattern III: diffuse cytoplasmic staining and there was a significant difference between immunostaining patterns of KIT and grades of MCTs (P = 0.004). The majority low grade MCT was KIT-staining pattern II (64.5%, 20/31), while the high grade MCT was KIT-staining pattern III (52.6%, 10/19). When the expression of KIT in MCT cells was II and III, the strong expression of Akt was noticed in cytoplasm in majority of MCT cells. In this study, three immunolabelling locations of p-Akt were found including cytoplasmic only, diffuse in cytoplasm with loose distribution in nucleus, and diffuse in cytoplasm with dense distribution in nucleus. There was a significant difference between immunostaining patterns of KIT and immunolabelling locations of p-Akt (P = 0.005). When the immunostaining pattern of KIT was pattern I, the major immunolabelling locations of p-Akt was cytoplasm only (70.0%, 7/10). However, when the immunostaining pattern of KIT was pattern III, the major immunolabelling locations of p-Akt was diffuse in cytoplasm and nucleus (61.5%, 8/13). A significant difference was observed between immunolabelling locations of p-Akt and metastasis (P = 0.001). The majority of p-Akt immunolabelling locations without MCT metastasis was cytoplasmic only (51.7%, 15/27), while the majority of p-Akt immunolabelling locations with MCT metastasis was diffuse in cytoplasm with dense distribution in nucleus (57.1%, 12/21). The overexpression and increase of activity of mTOR were showed when activity of p-Akt enhanced. This study highlighted the importance of KIT/PI3K/Akt/mTOR signaling pathway in canine cutaneous MCTs and p-Akt plays an important role in metastasis of MCTs.
URI: http://hdl.handle.net/11455/93041
其他識別: U0005-2811201416190083
文章公開時間: 10000-01-01
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