Barry Robert J, de Moura Letícia R, Marshall Jean-Claude, Fernandes Bruno F, Orellana Maria Eugenia, Antecka Emilia, Martins Claudia, Burnier Miguel N
Department of Ophthalmology and Pathology, The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Montreal, Canada.
Br J Ophthalmol. 2007 Nov;91(11):1532-6. doi: 10.1136/bjo.2007.119651. Epub 2007 Jun 25.
C-kit is a transmembrane tyrosine kinase protein thought to play an important role in tumourigenesis. With the development of the compound imatinib mesylate, which specifically inhibits tyrosine kinase receptors, C-kit has emerged as a potential therapeutic target. This study aims to determine the immunoexpression of C-kit in retinoblastoma and correlate this expression with histopathological prognostic features.
Eighty-four paraffin-embedded retinoblastomas were collected from the Henry C Witelson Ocular Pathology Registry. C-kit immunostaining was used according to the protocol provided by Ventana Medical System Inc., Arizona. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve and the degree of tumour differentiation. Odds ratios were calculated to quantify differences in C-kit expression between tumours with different patterns of invasion and differentiation.
Twenty-one slides (25%) were excluded from analysis because of the presence of extensive tissue necrosis or the absence of sufficient optic nerve tissue for analysis. Overall, C-kit expression was identified in 33/63 specimens analysed (52.38%). Two of the 13 tumours without choroidal or optic nerve invasion (15.4%) were positive for C-kit. C-kit expression was seen in 31 of the 50 tumours with extraretinal invasion (62%, p<0.01), 26 of 44 specimens with choroidal involvement (59.9%, p<0.2), and 20 of the 29 with optic nerve involvement (68.96%, p<0.02). Fourteen of 25 moderate or well-differentiated specimens (56%) and 19 of 38 undifferentiated specimens (50%) displayed positivity for C-kit (p>0.5).
More than half the retinoblastomas in this study expressed C-kit. The expression of C-kit strongly correlated with histopathological features of a worse prognosis including optic nerve and choroidal invasion.
C-kit是一种跨膜酪氨酸激酶蛋白，被认为在肿瘤发生过程中起重要作用。随着特异性抑制酪氨酸激酶受体的化合物甲磺酸伊马替尼的研发，C-kit已成为一个潜在的治疗靶点。本研究旨在确定C-kit在视网膜母细胞瘤中的免疫表达，并将这种表达与组织病理学预后特征相关联。
从亨利·C·威特森眼病理登记处收集了84例石蜡包埋的视网膜母细胞瘤。根据亚利桑那州Ventana医疗系统公司提供的方案进行C-kit免疫染色。免疫反应性与脉络膜和视神经浸润的有无以及肿瘤分化程度相关。计算优势比以量化不同浸润和分化模式的肿瘤之间C-kit表达的差异。
由于存在广泛的组织坏死或缺乏足够的视神经组织进行分析，21张切片（25%）被排除在分析之外。总体而言，在分析的63个标本中有33个（52.38%）鉴定出C-kit表达。13例无脉络膜或视神经浸润的肿瘤中有2例（15.4%）C-kit呈阳性。50例有视网膜外浸润的肿瘤中有31例（62%，p<0.01）可见C-kit表达，44例有脉络膜受累的标本中有26例（59.9%，p<0.2），29例有视神经受累的标本中有20例（68.96%，p<0.02）。25例中度或高分化标本中有14例（56%），38例未分化标本中有19例（50%）C-kit呈阳性（p>0.5）。
本研究中超过一半的视网膜母细胞瘤表达C-kit。C-kit的表达与包括视神经和脉络膜浸润在内的预后较差的组织病理学特征密切相关。
