Expression of integrin-linked kinase in adenoid cystic carcinoma of salivary glands correlates with epithelial-mesenchymal transition markers and tumor progression.

ABSTRACT

Integrin-linked kinase (ILK) plays a key role in cell-excellular matrix interactions mediated by integrins and several growth factors, regulating cell proliferation, apoptosis, differentiation, and migration. It has also been implicated in the development and progression in several malignancies involving epithelial to mesenchymal transition (EMT). However, the correlations between ILK and EMT markers and the progression of salivary adenoid cystic carcinoma (SACC) have not been well elucidated. Here, by immunohistochemistry, we studied the expression of ILK, Snail, E-cadherin, and N-cadherin in 94 SACC specimens and analyzed their correlations with clinicopathologic characteristics. Positive expression of ILK protein was detected in 76.6 % of the tumors. Increased expression of ILK and Snail and decreased E-cadherin expression correlated strongly with tumor solid type (P = 0.017, P = 0.008, and P = 0.038, respectively), advanced TNM stage (P = 0.021, P = 0.034, and P = 0.009, respectively), and increased risk of recurrence (P = 0.023, P = 0.011, and P = 0.039, respectively) and distant metastasis (P < 0.001, P < 0.001, and P = 0.001, respectively). Moreover, up-regulation of Snail and N-cadherin and down-regulation of E-cadherin correlated significantly with ILK over-expression (P < 0.001, P = 0.001, and P < 0.001, respectively) and a neural-invasive phenotype (P = 0.017, P = 0.002, and P < 0.001, respectively). Taken together, our results suggest that ILK may have an important role in progression and metastasis of SACC, possibly through EMT involving up-regulation of Snail and consequent aberrant expression of E-cadherin and N-cadherin. ILK should be considered as a potential therapeutic molecular target for patients with SACC.