The role of apoptosis in oral disease: mechanisms; aberrations in neoplastic, autoimmune, infectious, hematologic, and developmental diseases; and therapeutic opportunities.

Apoptosis is a genetically programmed form of cell death, which primarily functions to eliminate senescent or altered cells that are useless or harmful for the multicellular organism. Contrary to necrosis, apoptosis represents a physiologic cellular mechanism, normal function and control of which are critical for the development and homeostasis of multicellular organisms. In contrast, aberrations of the apoptotic mechanisms that cause excessive or deficient programmed cell death have been linked to a wide array of pathologic conditions. This review briefly summarizes the major apoptotic pathways and molecules and presents the most important oral diseases that are related to dysregulation of apoptosis. Knowledge of the association between aberrations in apoptotic mechanisms and human pathology hopefully will be implemented for the design of improved diagnostic and prognostic assays and the development of novel, more efficient, therapeutic strategies.

Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors.

On the basis of the heterogeneity of cytokeratins 7 and 20 expression in malignant epithelial tumors, the cytokeratin 7/20 immunophenotype has served as a useful diagnostic tool for discrimination of primary and/or metastatic carcinomas of unknown origin. However, the expression pattern of these cytokeratins in malignant salivary gland tumors has not been thoroughly studied. Our study material was composed of 84 malignant tumors of primary major or minor salivary gland origin. Nine histologic types of carcinoma were represented, including mucoepidermoid (26 cases), adenoid cystic (25), polymorphous low grade (11), salivary duct (8), acinic cell (4), ex mixed tumor (3), not otherwise specified (3), clear cell (2), and basal cell (2). In all, 13 cases of primary skin or mucosal squamous cell carcinoma with secondary salivary gland involvement were also examined. Immunoreactivity for cytokeratin 7 was evident in all malignant salivary gland tumors; the staining pattern was diffuse and strong in 62 cases, and focal and strong in 22 cases. In contrast, 78 cases were negative for cytokeratin 20, whereas only six cases (two mucoepidermoid, one adenoid cystic, and three salivary duct) displayed focal weak positivity. Overall, 92.9% of malignant salivary gland tumors were characterized by a cytokeratin 7 positive/20 negative immunoprofile, the remaining 7.1% of cases being positive for both cytokeratins. The latter phenotype was more common in salivary duct carcinomas (P< or =0.05). On the other hand, most squamous cell carcinomas (69%) were negative for both cytokeratins, while the remaining cases (31%) were negative for cytokeratin 20 and focally weakly positive for cytokeratin 7. We suggest that assessment of cytokeratin 7/20 immunoprofile may facilitate the differential diagnosis of (a) primary malignant salivary gland tumors from metastatic tumors, (b) metastatic salivary gland tumors, (c) primary salivary gland tumors, especially mucoepidermoid carcinomas, from squamous cell carcinomas, and (d) salivary duct carcinomas from other malignant salivary gland tumors.

Immunohistochemical evaluation of cell proliferation antigen Ki-67 and apoptosis-related proteins Bcl-2 and caspase-3 in oral granular cell tumor.

PURPOSE: We sought to evaluate the cell proliferation activity and immunohistochemical expression of proteins that promote or inhibit apoptosis in oral granular cell tumor (GCT). STUDY DESIGN: Immunohistochemistry for Ki-67, a cell proliferation marker; Bcl-2, an anti-apoptotic protein; and caspase-3, a protein implicated in the execution of apoptosis, was performed on tissues from 12 patients with GCT of the tongue. RESULTS: Nuclear immunostaining for Ki-67 was observed only in isolated GCs (less than 2%). All patients exhibited cytoplasmic immunoreactivity for Bcl-2 in the majority of tumor cells. Cytoplasmic staining for caspase-3 was also present in more than 50% of GCs in all tumors. CONCLUSIONS: GCT cells display low proliferation activity, a finding possibly related to their benign behavior. Caspase-3 expression suggests activation of the apoptotic cascade in the GCs, but persistence of the cells in the tissues could be attributed to the expression of Bcl-2 protein, a molecule that functions as a survival factor.