Cellular proliferation in canine cutaneous mast cell tumors:: Associations with c-KIT and its role in prognostication
Cellular proliferation in canine cutaneous mast cell tumors:: Associations with c-KIT and its role in prognostication
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DOI：
10.1354/vp.44-3-298
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发表时间：
2007-05-01
影响因子：
2.4
通讯作者：
Kiupel, M.
中科院分区：
文献类型：
--
作者：
Webster, J. D.;Yuzbasiyan-Gurkan, V.;Kiupel, M.
犬皮肤肥大细胞瘤(MCT)是犬常见的肿瘤性疾病。由于犬MCT的流行和该病不同的生物学行为，准确的预测和对MCT生物学的透彻了解对于该病的治疗至关重要。本研究的目的是评估和比较增殖标记物Ki67、增殖细胞核抗原(PCNA)和嗜银核仁组织区(AgNOR)作为犬MCTs独立预后标记物的有效性，并评价这些标记物的联合使用，因为每个标记物评估细胞增殖的不同方面。这项研究的另一个目的是评估细胞增殖和e-kit突变之间的关系，以及细胞增殖和犬MCT中异常KIT蛋白定位之间的关系。56例仅接受手术切除的MCT纳入本研究。用免疫组织化学方法检测Ki67表达、增殖细胞核抗原表达和KIT蛋白定位；用组织化学染色检测AgNOR计数；用聚合酶链式反应扩增检测是否存在内部串联复制c-kit突变。在这项研究中，Ki67和AgNOR计数的增加都与显著降低的存活率相关。在这些结果的基础上，我们建议对细胞增殖的评估，包括Ki67表达和AgNORs的评估，应该常规用于预测犬的MCTs。此外，这项研究的结果表明，具有异常KIT蛋白定位或内部串联复制c-KIT突变的MCT与细胞增殖增加有关，进一步表明c-KIT在犬MCT的进展中起作用。
Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and e-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.