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

Abstract

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.