Schwandner O, Bruch H P, Broll R
Department of Surgery, Medical University of Lübeck, Germany.
Int J Colorectal Dis. 2002 Jan;17(1):11-9. doi: 10.1007/s003840100333.
This study examined the prognostic value of the cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27Kip1, and the cell cycle regulating proteins cyclin D1 and p53 after curative surgery for rectal cancer.
Formalin-fixed, paraffin-embedded tissue samples of 160 rectal carcinomas resected curatively within a 5-year period were used. Immunohistochemical analysis used monoclonal antibodies p21(Waf1/Cip1) (clone SX118), p27Kip1 (clone SX53G8), cyclin D1 (clone DCS-6), and p53 (DO-1). Positive nuclear protein expression was assessed at the 10% level. Results of immunohistochemistry were studied for correlation with clinical and histopathological data of the prospective tumor registry including recurrence and patient survival.
Of the 160 rectal carcinomas 36% were p21(Waf1/Cip1) positive, 44% p27Kip1 positive, 48% cyclin D1 positive, and 39% p53 positive. The p21(Waf1/Cip1) staining pattern was correlated with p27Kip1 and p53 expression and with UICC stage and lymph node status. p53 status was not correlated to any clinical or histopathological variable. p27Kip1 expression was associated with tumor size and cyclin D1 expression. Tumor progression caused by local and distant recurrence occurred in 20%. p21(Waf1/Cip1), p27Kip1, and p53 were strong predictors of recurrence. p21(Waf1/Cip1) and p53 but not p27Kip1 were independently correlated with disease-free survival. UICC stage was independently related to both recurrence and survival. The best prognosis was in p21(Waf1/Cip1) positive and p53 negative rectal carcinomas.
Reflecting tumor biology by immunohistochemical assessment of cell cycle regulators, p21(Waf1/Cip1) and p53 were independently predictive of prognosis in rectal cancer, and p27Kip1 was independently related to recurrence. However, cyclin D1 had no independent relationship to prognosis. Clinically, UICC stage was a strong predictor of prognosis after curative surgery for rectal cancer.
本研究探讨了细胞周期蛋白依赖激酶抑制剂p21（Waf1/Cip1）和p27Kip1，以及细胞周期调节蛋白细胞周期蛋白D1和p53在直肠癌根治性手术后的预后价值。
使用在5年期间内根治性切除的160例直肠癌的福尔马林固定、石蜡包埋组织样本。免疫组织化学分析采用单克隆抗体p21（Waf1/Cip1）（克隆号SX118）、p27Kip1（克隆号SX53G8）、细胞周期蛋白D1（克隆号DCS-6）和p53（DO-1）。以10%的水平评估核蛋白阳性表达。研究免疫组织化学结果与前瞻性肿瘤登记处的临床和组织病理学数据（包括复发和患者生存情况）的相关性。
160例直肠癌中，36%为p21（Waf1/Cip1）阳性，44%为p27Kip1阳性，48%为细胞周期蛋白D1阳性，39%为p53阳性。p21（Waf1/Cip1）染色模式与p27Kip1和p53表达以及国际抗癌联盟（UICC）分期和淋巴结状态相关。p53状态与任何临床或组织病理学变量均无相关性。p27Kip1表达与肿瘤大小和细胞周期蛋白D1表达相关。20%发生了由局部和远处复发导致的肿瘤进展。p21（Waf1/Cip1）、p27Kip1和p53是复发的强有力预测指标。p21（Waf1/Cip1）和p53而非p27Kip1与无病生存期独立相关。UICC分期与复发和生存均独立相关。p21（Waf1/Cip1）阳性且p53阴性的直肠癌预后最佳。
通过对细胞周期调节因子进行免疫组织化学评估来反映肿瘤生物学特性，p21（Waf1/Cip1）和p53可独立预测直肠癌的预后，p27Kip1与复发独立相关。然而，细胞周期蛋白D1与预后无独立关系。临床上，UICC分期是直肠癌根治性手术后预后的强有力预测指标。
