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.

Twist expression in pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands

“…zhao et al demonstrated the expression of E-cadherin in normal salivary gland acinar cells with no expression of n-cadherin (26). regarding the mechanism of Twist in downregulation of E-cadherin, our finding is indirectly in the same line with that study (18).…”

“…Previous studies have demonstrated a reduction in E-cadherin expression in the majority of adCC cases in comparison with Pa, and also overexpression of this protein in benign salivary glands tumors (26,30). according to the explained mechanism of Twist in downregulation of E-cadherin, these findings indirectly supported the switching mechanism of Twist in salivary glands tumors (18 Several studies have demonstrated that Twist expression might be an independent prognostic factor which is useful for predicting patients' survival in breast cancer and melanoma (31,32).…”

Adenoid cystic carcinoma of the head and neck – An update

“…Expression of ILK correlates strongly with solid type AdCC, advanced TNM stage and increased risk of recurrence. Moreover, ILK over-expression and a neural invasive phenotype went along with downregulation of E-cadherin and upregulation of Snail and N-cadherin; by this mechanism ILK is believed to have a key role in progression and metastasis in AdCC [71].…”

Genomics of mucoepidermoid and adenoid cystic carcinomas

“…Ishii and colleagues demonstrated that in an adenoid cystic carcinoma mouse model, cancer cells lose epithelial markers such as E‐cadherin and gain the mesenchymal marker vimentin when undergoing metastases . Snail (SNA1) is a transcription factor that is known to repress E‐cadherin expression and lead to EMT; its expression is closely linked to prognosis, perineural invasion, tumor recurrence and tumor metastases …”