Janku Filip, Novotny Jan, Julis Ivan, Julisova Ivana, Pecen Ladislav, Tomancova Vera, Kocmanova Gabriela, Krasna Luboslava, Krajsova Ivana, Stork Jiri, Petruzelka Lubos
Department of Oncology, First Faculty of Medicine, General Teaching Hospital, Charles University, Prague, Czech Republic.
Melanoma Res. 2005 Aug;15(4):251-6. doi: 10.1097/00008390-200508000-00004.
The c-kit gene encodes a transmembrane receptor (KIT) with tyrosine kinase activity which is a specific target for anti-cancer therapy. We investigated KIT expression in a group of patients with early-stage malignant melanoma. Primary tumour specimens obtained from 261 radically resected patients with stage I and II malignant melanoma were examined for KIT expression. Formalin-fixed, paraffin embedded tissues were stained with the polyclonal rabbit anti-human anti-KIT antibody (Dako Cytomation Inc., Carpenteria, California, USA). Patients were classified into four groups according to the level of expression (0%, <30%, 30-60% and >60%). Univariate and multivariate analyses examining the impact of KIT expression, Breslow thickness, Clark level and microscopic ulceration on disease-free survival were performed. Within the population of 261 patients with early-stage melanoma with 62 recurrences during a follow-up of 64 months, KIT expression was found in 144 cases (55%). KIT was expressed in more than 60% of cells in 20 patients (8%), in 30-60% of cells in 64 patients (24%) and in less than 30% of cells in 60 patients (23%). KIT expression was not found in 117 patients (45%). In univariate analyses, the influence of KIT expression on disease-free survival was not proven (P=0.4956; log-rank test). Increasing Breslow thickness, a higher Clark level, the presence of microscopic ulceration and a higher stage were significantly associated with a shorter disease-free survival (P<0.0001; log-rank test in all cases). In multivariate analysis, Breslow thickness, stage and KIT expression were significant negative prognostic factors for a shorter disease-free survival (P<0.0001, P=0.0028, P=0.0488, respectively; stepwise Cox regression model). It can be concluded that KIT is expressed in more than one-half of early-stage malignant melanoma. KIT may serve as an additive prognostic factor to Breslow thickness and stage within the tested population. The therapeutic impact of KIT expression in malignant melanoma is uncertain. Results of ongoing pilot phase II studies may validate the efficacy of imatinib mesylate in malignant melanoma expressing KIT.
c-kit基因编码一种具有酪氨酸激酶活性的跨膜受体（KIT），它是抗癌治疗的一个特定靶点。我们调查了一组早期恶性黑色素瘤患者的KIT表达情况。对从261例接受根治性切除的I期和II期恶性黑色素瘤患者获取的原发性肿瘤标本进行KIT表达检测。用兔抗人KIT多克隆抗体（美国加利福尼亚州卡彭蒂亚市达科细胞公司）对福尔马林固定、石蜡包埋的组织进行染色。根据表达水平（0%、<30%、30 - 60%和>60%）将患者分为四组。进行单因素和多因素分析，以检验KIT表达、 Breslow厚度、Clark分级和微小溃疡对无病生存期的影响。在261例早期黑色素瘤患者群体中，随访64个月期间有62例复发，其中144例（55%）检测到KIT表达。20例患者（8%）的KIT在超过60%的细胞中表达，64例患者（24%）的KIT在30 - 60%的细胞中表达，60例患者（23%）的KIT在少于30%的细胞中表达。117例患者（45%）未检测到KIT表达。在单因素分析中，未证实KIT表达对无病生存期有影响（P = 0.4956；对数秩检验）。Breslow厚度增加、Clark分级较高、存在微小溃疡和分期较高与较短的无病生存期显著相关（P < 0.0001；所有病例均采用对数秩检验）。在多因素分析中，Breslow厚度、分期和KIT表达是无病生存期较短的显著负性预后因素（分别为P < 0.0001、P = 0.0028、P = 0.0488；逐步Cox回归模型）。可以得出结论，KIT在超过一半的早期恶性黑色素瘤中表达。在受试群体中，KIT可能是Breslow厚度和分期之外的一个附加预后因素。KIT表达在恶性黑色素瘤中的治疗意义尚不确定。正在进行的II期试验研究结果可能会验证甲磺酸伊马替尼对表达KIT的恶性黑色素瘤的疗效。
