犬肥大細胞瘤c-kit 表現與其他新興蛋白質表現之相關性

Abstract

肥大細胞瘤(MCTs)是犬最常見的皮膚腫瘤之一。目前最被認可的Patnaik system依據腫瘤細胞的分化程度將其分為三個等級，研究顯示此分級與腫瘤預後有很高的相關性。然而，此分級系統對於肥大細胞瘤的界定仍有模糊地帶，加上第二級肥大細胞瘤在臨床上良惡性表現差異極大，造成臨床預後預測上的困難。此外，雖然部分犬肥大細胞瘤的形成已被證實與KIT過度表現及其基因的突變有密切的關係，但絕大多數的肥大細胞瘤成因都還不清楚。因此，針對可能具有潛在相關性的因子做研究以獲得進一步提供預後或成因的資訊是有其必要性的。 本實驗針對72例犬肥大細胞瘤病例做分析,依照Patnaik system, modified Patnaik system和近年來發表的2-tiere scheme做組織學上的分級，配合免疫化學染色觀察Ki-67、DOG1、KMO和ENO1等新興蛋白質的表現，將其與KIT蛋白的表現、組織病理學的分級以及臨床上的預後做比較。 初步結果可以發現2-tier scheme可以有效的用於區分臨床上表現惡性的腫瘤，然而有一小部分的惡性腫瘤在判定上會發生低估的情形，是這個分級的其中一個缺點。免疫化學染色結果顯示在分化不良的腫瘤中DOG1和KMO的表現皆會下降，且與較短的存活率有關。不表現DOG1的肥大細胞瘤傾向於有較短的復發期；此外，ENO1表現量高的肥大細胞瘤傾向於有較短的存活中位期 (median survival time)。此實驗的初步結果，僅顯示這些新興蛋白質與肥大細胞瘤惡性程度之間之相關性，需要有進一步的研究確立此結果。

Mast cell tumors (MCTs) are one of the most common skin tumors in dogs. Although histological grading was an independent indicator for prognostic prediction, subjectivity in interpretation was considered as a major problem for a relatively low consistency in grading assignment. Moreover, great variation of biological behavior exhibited from grade II MCTs has been occupying a major component of the cases, impeding accurate prognosis prediction and has been regarded as a dilemma for deciding proper treatment strategies. Meanwhile, although KIT overexpression and c-kit mutation have been proven to be related to carcinogenesis of canine MCTs, the etiology remained unknown for most of the cases. Therefore, the necessity of exploring other potential parameters should be considered for advancing current information we’ve got. In this study, we evaluated the new proposed 2-tier grading systems in comparison with Patnaik system and modified Patnaik system. In addition, the emerging proteins including DOG1, KMO, Ki-67 and ENO1 were firstly investigated in the canine species for comparison with histological grading, KIT expression and clinical outcomes. Current results showed that the use of 2-tier scheme was of benefit for discriminating aggressive tumors, but underestimation could occur in a subset of the tumors. Immunohistochemistry demonstrated the tendency of decreased expression of DOG1 and KMO in poorly-differentiated tumors in association with an overall decreased survival time. Tumors with negative DOG1 expression tended to have a shorter median disease-free interval less than 10 days whereas tumors with strong ENO1 expressions tended to have a shorter median survival time than the others. This observation provided a preliminary data of regulation of the emerging proteins. Further investigation is needed for validation of the preliminary result.