Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma.

摘要

Integrin-linked kinase (ILK) is a key molecule involved in mediating several biological functions including cell-matrix interactions, angiogenesis, and invasion, as well as playing a role in epithelial to mesenchymal transition (EMT) in cancer cells. In ductal pancreatic adenocarcinoma, increased expression of ILK has been linked to tumor prognosis and correlated with increased chemoresistance to drugs, such as gemcitabine. However, the precise relationship between ILK, Snail, E-cadherin, and N-cadherin expression on the stepwise development of pancreatic cancer is unknown. Hence, the purpose of this work was to investigate levels of expression of ILK, Snail, and the cadherins in pancreatic intraepithelial neoplasia (PanIN), and cancer. Resection specimens of 25 randomly selected patients, who underwent a pyloric preserving pancreatoduodenectomy for ductal pancreatic adenocarcinoma, were utilized for this study. Formalin-fixed paraffin embedded pancreatic tissue was immunostained for ILK, E-cadherin, N-cadherin, and Snail by standard techniques. The extent of staining positivity was scored and the results correlated with clinicopathological parameters. In 23 of 25 cases, ILK expression showed extensive positivity (>50%), while two cases did not demonstrate any ILK staining. PanIN grades 1 (n = 16), 2 (n = 11), and 3 (n = 19) lesions demonstrated only focal positivity (<10%) for ILK. E-cadherin showed a reciprocal staining pattern to ILK in 21 of 25 cases, with only focal expression of the marker in pancreatic adenocarcinoma. Interestingly, 15 of 19 PanIN-3 lesions expressed extensive E-cadherin staining. N-cadherin, however, was moderately expressed in the majority of cases (n = 18). Snail expression (n = 22) correlated with ILK expression in ductal pancreatic adenocarcinoma (rho = 0.8168, p = 0.02), but only minimal Snail staining activity was detected in PanIN lesions. The increase in expression of the E-cadherin repressor Snail, as well as the related increase in the ILK expression, may point towards an ILK-mediated induction, opening possible avenues for targeted drug therapy.