Khalifeh Ibrahim, Munkarah Adnan R, Schimp Veronica, Morris Robert, Lawrence W Dwayne, Ali-Fehmi Rouba
Department of Pathology, Harper University Hospital, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Int J Gynecol Pathol. 2005 Jul;24(3):228-34. doi: 10.1097/01.pgp.0000164599.26969.8a.
The transmembrane-tyrosine-kinase receptor, c-kit, is involved in cell differentiation and has been found to be expressed in normal human cell types and solid tumors. This study was designed to investigate the effects of c-kit expression on: 1) tumor proliferation and apoptosis, and 2) survival in patients with high-grade advanced stage ovarian serous carcinoma (OSC). We identified 118 patients with high-grade advanced stage OSC from our files. Clinical data, including demographics and overall survival, were collected. Immunohistochemical panel consisting of c-kit, ki-67, p53, and bcl-2 was performed. C-kit was categorized as positive if any cytoplasmic or membranous staining pattern was identified. Correlation between c-kit expression and the other markers was performed. Survival analysis was performed using COX proportional hazards regression and Kaplan-Meier test. Of 118 cases, 25 (21.2%) expressed c-kit. Of 93 c-kit-negative tumors, 87.1% had a high proliferation index. High p53 and bcl-2 expression was identified in 96 (81.4%) and 59 (50%) cases respectively. No significant statistical correlation was identified between c-kit and apoptosis markers. Tumors lacking c-kit expression showed a trend toward having high proliferation index, but this did not achieve statistical significance (p = 0.07). Of the seven variables included in the multivariate survival analysis, only c-kit (odds ratio, 2.12; 95% confidence interval, 08-4.17; p = 0.02) and ki-67 (odds ratio, 1.9; 95% confidence interval, 1.1-3.1; p = 0.03) showed an independent statistically significant impact on survival. High-grade advanced stage OSC lacking c-kit expression correlates with poor outcome. Interestingly, cases lacking c-kit expression also showed a trend to have high proliferation index.
跨膜酪氨酸激酶受体c-kit参与细胞分化,已发现其在正常人类细胞类型和实体瘤中表达。本研究旨在调查c-kit表达对以下两方面的影响:1)肿瘤增殖和凋亡;2)高级别晚期卵巢浆液性癌(OSC)患者的生存情况。我们从病历中识别出118例高级别晚期OSC患者。收集了包括人口统计学和总生存情况在内的临床数据。进行了由c-kit、ki-67、p53和bcl-2组成的免疫组织化学检测。如果发现任何细胞质或膜染色模式,则将c-kit分类为阳性。对c-kit表达与其他标志物之间的相关性进行了分析。使用COX比例风险回归和Kaplan-Meier检验进行生存分析。在118例病例中,25例(21.2%)表达c-kit。在93例c-kit阴性肿瘤中,87.1%具有高增殖指数。分别在96例(81.4%)和59例(50%)病例中发现高p53和bcl-2表达。未发现c-kit与凋亡标志物之间存在显著的统计学相关性。缺乏c-kit表达的肿瘤显示出具有高增殖指数的趋势,但这未达到统计学显著性(p = 0.07)。在多变量生存分析纳入的七个变量中,只有c-kit(比值比,2.12;95%置信区间,0.8 - 4.17;p = 0.02)和ki-67(比值比,1.9;95%置信区间,1.1 - 3.1;p = 0.03)对生存有独立的统计学显著影响。缺乏c-kit表达的高级别晚期OSC与不良预后相关。有趣的是,缺乏c-kit表达的病例也显示出具有高增殖指数的趋势。