Lee Sun-Joo, Kim Hye Sun, Kim Hy Sook, Chun Yi Kyung, Hong Sung Ran, Lee Je-Ho
Department of Obstetrics and Gynecology, Konkuk University Hospital, Konkuk University School of Medicine, Seoul 143-729, South Korea.
Hum Pathol. 2007 Aug;38(8):1226-31. doi: 10.1016/j.humpath.2007.01.012. Epub 2007 May 8.
Uterine carcinosarcomas (UCs) are highly aggressive neoplasms for which no effective adjuvant therapy has been established. The aim of this study was to test potential indicators of UC sensitivity to topoisomerase I (topo I)-targeted drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs is dependent on topo I expression, DNA replication rate, and activity of the apoptotic pathway. Therefore, this study investigated expression of topo I, a proliferation marker Ki-67, and the apoptosis initiator p53 in 20 cases of UC. Formalin-fixed paraffin-embedded tissue sections were immunostained with monoclonal antibodies against topo I, Ki-67, and p53. The hospital records of all 20 patients with UC were reviewed. Twelve (60%) of 20 cases showed increased expression of topo I. Staining for Ki-67 showed elevated expression in 15 (75%) of 20 cases. Fourteen cases (70%) showed positive staining for p53 in more than 20% of the tumor cells. However, analysis of the relationship between immunohistochemical results and clinical parameters revealed no correlations with topo I expression. There were no significant correlations between the expression of topo I and Ki-67 (P = .704), or topo I and p53 (P = .465). Significantly increased expression of topo I, Ki-67, and p53 in UC tumor cells suggests sensitivity to topo I-targeted drug treatment.
子宫癌肉瘤(UCs)是极具侵袭性的肿瘤,目前尚未确立有效的辅助治疗方法。本研究的目的是测试UC对靶向拓扑异构酶I(topo I)药物敏感性的潜在指标。实验室研究表明,细胞对靶向topo I药物的反应取决于topo I表达、DNA复制速率和凋亡途径的活性。因此,本研究调查了20例UC中topo I、增殖标志物Ki-67和凋亡启动因子p53的表达情况。用抗topo I、Ki-67和p53的单克隆抗体对福尔马林固定石蜡包埋的组织切片进行免疫染色。回顾了所有20例UC患者的医院记录。20例中有12例(60%)显示topo I表达增加。Ki-67染色显示20例中有15例(75%)表达升高。14例(70%)在超过20%的肿瘤细胞中p53染色呈阳性。然而,免疫组化结果与临床参数之间的分析显示与topo I表达无相关性。topo I与Ki-67的表达之间(P = 0.704)或topo I与p53的表达之间(P = 0.465)均无显著相关性。UC肿瘤细胞中topo I、Ki-67和p53表达显著增加表明对靶向topo I的药物治疗敏感。