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犬皮肤肥大细胞瘤中c-KIT信使核糖核酸和蛋白质表达及突变:与术后预后的相关性

c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast cell tumors: correlations with post-surgical prognosis.

作者信息

Giantin Mery, Vascellari Marta, Morello Emanuela Maria, Capello Katia, Vercelli Antonella, Granato Anna, Lopparelli Rosa Maria, Nassuato Chiara, Carminato Antonio, Martano Marina, Mutinelli Franco, Dacasto Mauro

机构信息

Dipartimento di Sanità pubblica, Patologia comparata ed Igiene veterinaria, Area di Farmacologia e Tossicologia, viale dell'Università 16, I-35020 Agripolis Legnaro, Padova, Italy.

出版信息

J Vet Diagn Invest. 2012 Jan;24(1):116-26. doi: 10.1177/1040638711425945. Epub 2011 Dec 6.

Abstract

Cutaneous mast cell tumors (MCTs) are among the most common neoplasms in dogs and show a highly variable biologic behavior. Histological grading, cell proliferation markers, and KIT immunohistochemistry are typically used to predict post-surgical prognosis. In the present study, c-KIT messenger RNA (mRNA) expression was measured in canine MCTs and its relationship with tumor grade, immunohistochemical staining pattern, post-surgical prognosis, and mutations was investigated. A significant increase of c-KIT mRNA was observed in MCTs versus healthy skin and surgical margins. Mutations were observed in 8.3% of cases. The KIT staining pattern was investigated for both grading systems. In particular, staining pattern III was associated with grade II (G2) and G3 MCTs, while staining patterns I and II were associated with G1 and G2 MCTs. Considering the 2-tier histological grading, the high grade was mainly associated with pattern III (71%) while the low grade was associated with patterns II (70%) and I (28%). A weak association between the KIT staining pattern and outcome was also observed. The results obtained suggest that c-KIT mRNA is overexpressed in canine MCT, although the fold variations were not associated with the protein localization or complementary DNA mutations. These observations suggested that the 3 events were independent. The histological grading and the KIT staining pattern have prognostic value as previously published. Staining pattern I could be especially helpful in predicting a good prognosis of G2 MCTs. Sequence mutations were not necessarily suggestive of a worse prognosis, but might be useful in choosing a chemotherapy protocol.

摘要

皮肤肥大细胞瘤(MCTs)是犬类最常见的肿瘤之一,其生物学行为高度可变。组织学分级、细胞增殖标志物和KIT免疫组化通常用于预测手术后的预后。在本研究中,检测了犬MCTs中c-KIT信使核糖核酸(mRNA)的表达,并研究了其与肿瘤分级、免疫组化染色模式、手术后预后及突变的关系。与健康皮肤和手术切缘相比,MCTs中观察到c-KIT mRNA显著增加。在8.3%的病例中观察到突变。对两种分级系统均研究了KIT染色模式。特别是,染色模式III与II级(G2)和G3 MCTs相关,而染色模式I和II与G1和G2 MCTs相关。考虑到两级组织学分级,高级别主要与模式III(71%)相关,而低级别与模式II(70%)和I(28%)相关。还观察到KIT染色模式与预后之间存在弱关联。所得结果表明,c-KIT mRNA在犬MCT中过度表达,尽管倍数变化与蛋白质定位或互补DNA突变无关。这些观察结果表明这三个事件是独立的。如先前发表的那样,组织学分级和KIT染色模式具有预后价值。染色模式I可能对预测G2 MCTs的良好预后特别有帮助。序列突变不一定提示预后更差,但可能有助于选择化疗方案。

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