Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer
Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer
复制标题
DOI：
10.1245/s10434-012-2216-7
复制
发表时间：
2012-07-01
影响因子：
3.7
通讯作者：
Meijer, Gerrit A.
中科院分区：
文献类型：
--
作者：
Belt, Eric J. Th;Brosens, Rebecca P. M.;Meijer, Gerrit A.
目的.探讨多种细胞周期相关蛋白在大量II期和III期结肠癌中的预后价值。从386例II期和III期结肠癌患者的福尔马林固定、石蜡包埋的肿瘤样本中分离DNA并构建组织微阵列。对组织微阵列载玻片进行p21、p27、p53、表皮生长因子受体、Her 2/Neu、β-连环蛋白、细胞周期蛋白D1、Ki-67、胸苷酸合成酶和极光激酶A（AURKA）的化学染色。采用聚合酶链反应分析微卫星不稳定性，对蛋白质表达进行分层。总的来说，低p21、高p53、低cyclin D1和高AURKA表达与复发显著相关（分别为P = 0.01、P < 0.01、P = 0.04和P < 0.01）。在未接受辅助化疗的II期患者（n = 190）中，观察到p21低表达和p53高表达肿瘤的复发率显著更高（分别为P < 0.01和P = 0.03）。在未接受化疗的III期患者中，p53高表达与复发相关（P = 0.02），而在接受化疗的患者中，AURKA高表达与复发相关（P < 0.01）。在微卫星稳定性肿瘤患者中，高水平的p53和AURKA与复发相关（分别为P = 0.01和P < 0.01）。多变量分析显示p21（比值比1.6，95%置信区间0.9-2.8）和AURKA（比值比2.7，95%置信区间1.3-5.6）与疾病复发独立相关。结论。p21、p53、cyclin D1和AURKA可作为结肠癌复发高危患者的预后指标。
Purpose. To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers.Methods. From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, beta-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction-based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status.Results. Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P < 0.01, P = 0.04, and P < 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and high-p53-expressing tumors (P < 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P < 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P < 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9-2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3-5.6) to be independently associated with disease recurrence.Conclusions. p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.