Increased expression of ALDH-1 is associated with clinical parameters of salivary glands neoplasms

Abstract

The enzyme aldehyde dehydrogenase-1 (ALDH-1) is a known putative tumour stem cells (TSC) marker, and these cells are implicated in carcinogenesis and progression of human neoplasms. We aimed to evaluate ALDH-1 expression in benign and malignant salivary gland neoplasms and its clinicopathological and prognostic significance. Expression of ALDH-1 was investigated by immunohistochemistry and confirmed by Western Blot analysis in 154 salivary gland neoplasms (103 malignant and 51 benign neoplasms). The expression was identified in the parenchyma of malignant (n = 88; 85.6%) and benign (100%) neoplasms. Overall, expression in the parenchyma varied considerably and was not associated with clinical parameters in most malignant neoplasms, however, a high expression in mucoepidermoid carcinomas (MEC) was associated with advanced pathological TNM stage (p = 0.047). The presence of ALDH-1 in stromal cells of malignant neoplasms (n = 67; 65.0%) was associated with lymph node metastasis (p = 0.032), tumour recurrence (p = 0.006) and death (p = 0.013). Overall and disease-free survival in 5 and 10 years was lower in patients with diagnosis of adenoid cystic carcinoma, tumour recurrence, advanced staging, and presence of ALDH-1 in the stroma. When adjusted by multivariate analysis, advanced staging and stromal expression were independent prognostic factors affecting disease-free survival. Our findings provide evidence that cells characterized as TSC in the parenchyma and stroma are differentially present among the different types of neoplasms studied and may be related to tumourigenesis, biological behaviour and persistence capacity of malignant tumours of the salivary gland.