Cancer stem‐like cells in adenoid cystic carcinoma of salivary glands: relationship with morphogenesis of histological variants

Abstract

Adenoid cystic carcinoma (AdCC) is a common malignant salivary gland tumor. AdCC is histologically characterized as having cribriform, tubular and solid patterns, and production of excess extracellular matrix (ECM). Cancer stem cells (CSCs) are defined cells within a tumor that possess the capacity to self-renew and to induce the heterogeneous lineages of cancer cells that comprise the tumor. To examine the morphogenetic relationship between CSCs and the growth patterns in AdCC, we employed formalin-fixed and paraffin-embedded 26 cases of AdCC and immunohistochemically clarified the distribution of CSCs using CD133 and CD44 antibodies. CD133- or CD44-positive cancer stem (CS)-like cells were scattered in the pseudocyst-lining area of cribriform patterns having a Swiss cheese-like appearance. However, based on the further overproduction of ECM, CS-like cells accumulate in thin epithelial cords or trabecular arrangements. These CS-like cell aggregations are considered to form two cell-layered tubular patterns. Moreover, proliferation of outer cells in tubular patterns leads to cribriform patterns or solid patterns in the presence of excess ECM production or a lack of ECM overproduction, respectively. CS-like cells in AdCC were frequently located at the border areas adjacent to ECM, with exception of some cribriform and solid variants. It is suggested that CSCs included in CD133- or CD44-positive cells play an important role in morphogenesis of salivary AdCC, especially in transition among the histological growth patterns. ECM is well known as a component of the CSC microenvironment, and ECM may regulate morphogenesis of AdCC through the stimulation of CSCs.