Li Zhi-xun, Zeng Sui-de, Liu Yong-dong, Liao Yi-ji, Hua Wen-feng, Lin Feng, Xie Dan
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2009 Mar;12(2):185-8.
To investigate the clinicopathological value of the expression and amplification of P21-activated kinase 1 gene (PAK1) in colorectal carcinoma(CRC).
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.
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(G(3)) CRCs, PAK1 expression in 90% carcinoma was up-regulated, which was significantly higher than that in tumors of G(1/2)(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.
Overexpression of PAK1 protein may play an important role in development and progression of colorectal neoplasms and it is closely associated with the malignant histological and invasive phenotype of CRCs. The expression of PAK1 in CRC may be used as one of the new molecular markers in predicting tumors malignant potential and progression.
探讨P21激活激酶1基因（PAK1）在结直肠癌（CRC）中的表达及扩增的临床病理价值。
采用免疫组织化学（IHC）、荧光原位杂交（FISH）和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL），通过组织芯片检测80例结直肠癌和30例大肠腺瘤中PAK1的蛋白表达、扩增情况及细胞凋亡情况。
免疫组织化学显示，26%的大肠腺瘤和62%的结直肠癌中PAK1蛋白呈过表达。PAK1表达与肿瘤组织学分级及临床分期之间存在显著相关性（P<0.05）。在低分化（G(3)）结直肠癌中，90%的癌组织中PAK1表达上调，显著高于G(1/2)肿瘤（51%）。在临床晚期（Dukes C、D期）的结直肠癌中，78%检测到PAK1过表达，显著高于临床早期（Dukes A、B期，53%）。此外，在这些结直肠癌队列中观察到PAK1过表达与细胞凋亡呈负相关（P<0.05）。荧光原位杂交显示，仅3%的结直肠癌中检测到PAK1基因扩增。
PAK1蛋白过表达可能在结直肠肿瘤的发生发展中起重要作用，且与结直肠癌的恶性组织学和侵袭表型密切相关。结直肠癌中PAK1的表达可作为预测肿瘤恶性潜能和进展的新分子标志物之一。
