Shvarts Oleg, Seligson David, Lam John, Shi Tao, Horvath Steve, Figlin Robert, Belldegrun Arie, Pantuck Allan J
Department of Urology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California 90095-1738, USA.
J Urol. 2005 Mar;173(3):725-8. doi: 10.1097/01.ju.0000152354.08057.2a.
We determined which clinical and molecular variables can predict cancer recurrence in patients following surgical management for localized renal cell carcinoma (RCC).
From a custom kidney cancer tissue microarray containing tumors specimens from 350 patients 193 undergoing nephrectomy for localized RCC at our institution between 1989 and 2000 were identified. The array was then analyzed by immunohistochemistry for certain molecular markers, namely CA9, CA12, Ki67, gelsolin, p53, EpCAM, pTEN and vimentin. The medical records of these patients were then reviewed for age, sex, TNM stage, tumor size, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status, recurrence status and, when applicable, time to recurrence. Cox regression analyses were done to determine clinical and molecular predictors of time to tumor recurrence.
Of the patients 15% demonstrated evidence of tumor recurrence following nephrectomy (29 of 193). Univariate Cox regression demonstrated that tumor size, T stage, grade, ECOG performance status, Ki67, EpCAM and p53 were significantly associated with recurrence (p <0.05). A multivariate Cox regression model showed that T stage (p = 0.018), ECOG (p = 0.004) and p53 (p = 0.003) were the 3 most significant predictors. p53 expression correlated significantly with nuclear grade (Pearson correlation 0.22, p = 0.023) but not with any other clinical factors. Patients with localized tumors demonstrating mean p53 staining values above and below 20% of cells had recurrence rates of 37.7% and 14.4%, respectively (RR = 3.28, p = 0.018).
p53 is a significant molecular predictor of tumor recurrence, as identified in patients undergoing treatment for localized RCC.
我们确定了哪些临床和分子变量能够预测局限性肾细胞癌(RCC)患者手术治疗后的癌症复发情况。
从一个定制的肾癌组织芯片中选取肿瘤标本,该芯片包含了1989年至2000年间在我们机构接受局限性RCC肾切除术的350例患者的样本,其中193例被纳入研究。然后通过免疫组织化学分析该芯片,检测某些分子标志物,即CA9、CA12、Ki67、凝溶胶蛋白、p53、上皮细胞黏附分子(EpCAM)、第10号染色体缺失的磷酸酶及张力蛋白同源物(pTEN)和波形蛋白。随后查阅这些患者的病历,记录其年龄、性别、TNM分期、肿瘤大小、核分级、东部肿瘤协作组(ECOG)体能状态、复发情况以及(如适用)复发时间。进行Cox回归分析以确定肿瘤复发时间的临床和分子预测因素。
在这些患者中,15%(193例中的29例)在肾切除术后出现肿瘤复发迹象。单因素Cox回归分析表明,肿瘤大小、T分期、分级、ECOG体能状态、Ki67、EpCAM和p53与复发显著相关(p<0.05)。多因素Cox回归模型显示,T分期(p = 0.018)、ECOG(p = 0.004)和p53(p = 0.003)是3个最显著的预测因素。p53表达与核分级显著相关(Pearson相关系数为0.22,p = 0.023),但与任何其他临床因素均无相关性。局限性肿瘤患者中,p53染色细胞均值高于和低于20%的患者复发率分别为37.7%和14.4%(相对危险度=3.28,p = 0.018)。
p53是局限性RCC患者治疗后肿瘤复发的一个重要分子预测因素。