Cellular basis and clinical implications of biological markers in salivary tissues: their topological distribution in murine submandibular gland.

Cell proliferation and apoptosis as well as cell-cell adhesion and communication are essential processes that assure cell survival, renewal and coordination. Since junctional proteins have a tumor suppressor activity, their immunohistochemical characterization has diagnostic and prognostic value. The purpose of this report is to review the role played by junctional and proliferation-related proteins in the salivary glands and to illustrate their immunohistochemical localisation in normal murine submandibular gland. Normal salivary gland tissue was obtained from normal adult male BALB/c mice. After immediate fixation in formalin and ethanol, the samples were immunohistochemically stained for E-cadherin (HECD-1), Bcl-2, Ki67 (MIB-1), connexin26 and connexin 32, beta-catenin and gamma-catenin. Their topological distribution and reactivity were evaluated by light microscopy. The nuclei of submandibular acinar cells exhibited low to moderate staining for Ki67, but no reaction was observed in ductal cells. Murine Bcl-2 was light to moderately expressed in the latero-basal domain of cells of submandibular acini but was only lightly expressed in striated and eosinophilic ducts. The lateral domain of acinar cells were heavily stained with anti-E-cadherin, while only low levels were expressed at the cellular surface of ducts. beta-Catenin was consistently and evenly distributed along the latero-apical boundaries of eosinophilic secretory duct cells as well as on the lateral domain of acinar cells. On the contrary, gamma-catenin was generally expressed at lower levels than beta-catenin, was not expressed in ductal cells and was only lightly stained on the lateral membranes of acinar cells. No expression of connexin 32 was observed in ducts but it was significantly expressed in a spotted pattern along the plasma membrane of acinic cells. Connexin 26 showed similar localization to that of connexin 32 but the staining was much more intense. Since these proteins have been reported to play key roles in maintaining homeostasis via control of cell growth, differentiation and death, their analysis in normal salivary tissue will hopefully contribute to the study of salivary tumorigenesis.