结直肠癌中P21-激活激酶1基因表达与扩增及其临床病理学意义

目的探讨P21-激活激酶1（PAK1）基因在结直肠癌（CRC）中的表达与扩增及其临床病理学意义。方法运用免疫组织化学（免疫组化）、荧光原位杂交和末端脱氧核苷酸转移酶介导缺口末端标记方法，检测PAK1基因在80例CRC和30例结直肠良性腺瘤组织芯片中的表达、扩增及其细胞凋亡情况。结果免疫组化结果显示，26％的结直肠良性腺瘤和62％的CRC出现PAK1蛋白过度表达。CRC中PAK1蛋白表达与肿瘤组织学分级、临床分期均有显著相关性（P〈0．05）。90％低分化（G3级）CRC中出现PAK1蛋白过度表达，显著高于中一高分化CRC（G1/2级）的51％；78％的临床晚期（Dukes C、D期）CRC组织呈PAK1蛋白过度表达，也显著高于临床早期（Dukes A、B期）的53％。PAK1蛋白在CRC中的表达与肿瘤细胞凋亡指数（AI）呈显著负相关（P〈0．05）。荧光原位杂交检测发现，只有3％的CRC出现PAKI基因扩增。结论PAK1蛋白过度表达可能在结直肠肿瘤的发生发展中起重要作用，而且与CRC的组织学和临床浸润表型密切相关，可作为判断CRC恶性程度与进展的新分子标记物之一。

Clinicopathological significance of expression and amplification of P21-acticated kinase 1 gene in colorectal carcinoma

Objective To investigate the clinicopathological value of the expression and amplification of P21-activated kinase 1 gene (PAK1) in colorectal carcinoma (CRC). Methods Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) methods were used to examine the protein expression, amplification of PAK1 and cell apoptosis in 80 cases of CRC and 30 cases of colorectal adenoma by tissue microarray. Results IHC showed an overexpression of PAK1 protein in 26% of colorectal adenomas and 62% of CRCs. Significant association was found between expression of PAK1 and tumor histological grade as well as tumor clinical stage (P<0.05). In poor-differentiated(G3) CRCs, PAK1 expression in 90% carcinoma was up-regnlated, which was significantly higher than that in tumors of G1/2 (51%). Overexpression of PAK1 was detected in 78% of CRCs in later clinical stages (Dukes C, D), which was significantly higher than that in early clinical stages (Dukes A,B, 53%). In addition, negative correlation between PAK1 overexpression and cell apoptosis was observed in these CRC cohorts (P<0.05). FISH revealed that amplification of PAK1 gene was examined in only 3% CRCs. Conclusions Overexpression of PAK1 protein may play an important role in development and progression of coloreetal neoplasms and it is closely associated with the malignant histological and invasive phenotype of CBCs. The expression of PAK1 in CBC may be used as one of the new molecular markers in predicting tumors malignant potential and progression.