p57^(Kip2)和Ki-67在壶腹癌中的表达及意义

The Expression of p57^(Kip2) and Ki-67 in Carcinomas of the Ampulla of Vater

目的:研究壶腹癌中p57Kip2和Ki-67的表达及其与肿瘤的发生和进展的关系。方法:采用免疫组织化学ABC法检测46 例原发性壶腹癌,4例壶腹部腺瘤和8例壶腹部正常组织手术切除标本的p57Kip2和Ki-67表达水平。结果:46例壶腹癌的p57Kip2标志指数(labeling index,LI)平均为44.8%±24.6%,明显低于壶腹部正常上皮64.9%±11.3%(P=0.017)。腺瘤的p57Kip2LI平均为62.3%±2.8%,与正常上皮表达相比无显著差异。p57Kip2LI在淋巴结转移(33.2%vs 57.5%;P=0.001), 十二指肠浸润(40.8%vs 59.3%;P=0.04),胰腺浸润(38.9%vs 55.9%;P=0.019)以及高TNM分期(Ⅲ期或Ⅳ期vs Ⅰ期或Ⅱ期,33.2%vs 57.5%;P=0.001)病例中显著降低。Ki-67高表达与壶腹癌的淋巴结转移(69.7%vs 49.2%;P=0.001 2),十二指肠浸润(64.7%vs 42.6%;P=0.006),胰腺浸润(65.8%vs 48.8%;P=0.012),高TNM分期(Ⅲ期或Ⅳ期vs Ⅰ期或Ⅱ期,69.7%vs 49.2%;P=0.0012)呈显著相关。p57Kip2表达与Ki-67表达呈负相关(P=0.001)。结论:在壶腹癌的发生和进展过程中,p57Kip2失活不是一个早期基因事件,而是一个相对较晚的事件,与肿瘤的进展和淋巴结转移相关。Ki-67是反映壶腹癌进展的一个重要指标。

Objective:To investigate p57Kip2 and Ki-67 expression in human carcinomas and adenomas of the ampulla of vater. Methods: We examed the expression of p57Kip2 and Ki-67 immunohistochemically in 8 normal ampullas,4 adenomas, and 46 adenocarcinomas of the ampulla of vater by using avidin - biotin complex method. Results: The p57Kip2 labeling index (LI) in adenocarcinomas of the ampulla of vater was 44. 8% ± 24. 6% averagely, and was significantly lower than in normal ampullas (64.9% ± 11.3%,P = 0.017). The p57Kip2 LI in adenomas was 62.3% ±2.8% averagely, and was not significantly changed compared to the normals. p57Kip2 LI was significantly reduced in cases with lymph node metastasis (33.2% vs 57.5%; P = 0. 001), invasion of duodenal wall (40. 8% vs 59. 3% ; P = 0. 04), invasion of pancreatic parenchyma (38. 9% vs 55. 9%;P = 0.019) and advanced TNM stage (Ⅲ and Ⅳ vs Ⅰ and Ⅱ ,33.2% vs 57. 5%; P = 0.001). However, high Ki-67 LI was significantly correlated with tumor lymph node metastasis (69. 7% vs. 49. 2% ;P = 0. 0012) .invasion of duodenal wall (64. 7% vs. 42. 6%;P= 0. 006),invasion of pancreatic parenchyma (65. 8% vs. 48. 8%;P = 0. 012) and advanced TNM stage (Ⅲ and Ⅳ vs. Ⅰ and Ⅱ ,69. 7% vs. 49. 2% ;P = 0. 0012). The expression of p57Kip2 was inversely correlated with Ki-67 expression (P = 0. 001). Conclusion: The down-regulation of p57Kip2 is a common event in carcinogenesis of the Ampulla of Vater. Dysfunction of p57Kip2 is a late event contributed to tumor malignant progression and lymph metastasis in this kind of tumors. The Ki-67 index is a useful marker for tumor progression of carcinoma of the Ampulla of Vater.