Mechanisms underlying cancer progression caused by ezrin overexpression in tongue squamous cell carcinoma.

BACKGROUND: Ezrin is a member of the ezrin, radixin, and moesin family that provides a functional link between the plasma membrane and the cortical actin cytoskeleton. A correlation between ezrin overexpression and aggressive cancer behavior has been recently reported in various tumor types. However, its roles in the mechanisms underlying progression of tongue squamous cell carcinoma (SCC) are unclear. METHOD: We used human tongue SCC and noncancerous tissue microarrays to immunohistochemically analyze the ezrin expression level and its relationship with proliferative activity. The human tongue SCC cell line HSC-3 was used to determine the effects of ezrin RNA interference (RNAi) on cancer cells during MTT; wound healing and invasion assays; immunofluorescence of the actin cytoskeleton; and western blotting of E-cadherin, N-cadherin, ß-catenin, and the active and total RhoA/Rac1/cdc42. RESULTS: Ezrin was overexpressed in 46.4% of the tumors examined in human tongue SCC tissue microarrays. Ezrin expression was correlated with the Ki-67 index. Ezrin depletion by RNAi in the HSC-3 cells significantly reduced cell proliferation, migration, and invasiveness and disturbed actin reorganization during podia formation. Its effects on RhoA/Rac1/cdc42 expression were not significant, whereas it enhanced E-cadherin and ß-catenin expression and decreased N-cadherin expression. CONCLUSIONS: Ezrin is often overexpressed in primary tongue SCCs and may have an important role in their growth, migration, and invasiveness possibly via its relationship with the E-cadherin/ß-catenin complex and the cadherin switch. Thus, ezrin could be a therapeutic target in tongue SCC.

Pigmented keratocystic odontogenic tumor: A case report with review of the literature.

Keratocystic odontogenic tumor (KCOT) is a relatively rare benign neoplasm of odontogenic origin. The squamous epithelium of KCOT usually does not contain melanocytes, however, pigmented KCOT has been documented, albeit extremely rarely. In the present study, we described an additional case of pigmented KCOT and review the clinicopathological features of this extremely rare lesion. A 23-year-old Japanese female presented with a relatively well-circumscribed round unilocular radiolucency that impacted the third molar in her right mandibula. Surgical resection was performed subsequent to a clinical diagnosis of KCOT. Histopathological study of the resected mandibular cyst showed that it was covered by a parakeratinized stratified squamous epithelium, which had slightly enlarged hyperchromatic nuclei. On the luminal surface, a wavy layer of parakeratin was observed. In addition, dendritic melanocytes without atypia were observed in approximately half of the squamous epithelium. Immunohistochemical analyses revealed that these melanocytes were positive for S-100 protein, Melan-A and HMB-45. Therefore, a diagnosis of pigmented KCOT was made. Review of the clinicopathological features of the previously reported cases of pigmented KCOT as well as the present case revealed that: i) this lesion occurs mostly in young persons (average age, 18 years) and shows female predominance; ii) most cases are solitary and involve the mandibula; and iii) the reported incidence is 0.36-10.6% and this difference may be associated with ethnicity. Thus, we described the ninth reported case of pigmented KCOT. The mechanism by which melanocytes appear and the difference in ethnic prevalence remain unclear. Additional clinicopathological studies are needed to clarify these issues.

Histological examination of the relationship between respiratory disorders and repetitive microaspiration using a rat gastro-duodenal contents reflux model.

Microaspiration due to gastroesophageal reflux (GER) has been suggested as a factor contributing to the development and exacerbation of several respiratory disorders. To explore the relationship between GER and respiratory disorders, we histologically examined the bilateral lungs of a rat gastroduodenal contents reflux model, which was previously used to investigate the histogenesis of Barrett's esophagus and esophageal carcinoma. GER was surgically induced in male Wistar rats. The bilateral lungs of the reflux rats were examined with hematoxylin and eosin (HE), PAS-Alcian blue, and Azan staining at 10 and 20 weeks after surgery. Immunohistochemical staining of CD68 and α-SMA was also performed. Aspiration pneumonia with severe peribronchiolar neutrophilic and lymphocytic infiltrates, goblet cell hyperplasia, prominence of blood vessels, and increased thickness of the smooth muscle layer were detected. Bronchiolitis obliterans (BO)-like lesions comprising granulation tissue with macrophages, spindle cells, and multinucleated giant cells in the lumen of respiratory bronchioles were observed in the bilateral lungs of the reflux animals. These findings suggest that the severe inflammation and the BO-like lesions may play a role in exacerbation of the forced expiratory volume in 1 second (FEV 1) in human cases. In conclusion, we speculate that repetitive microaspiration due to GER may contribute to the exacerbation of various respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD), and the development of BO syndrome following lung transplantation. The reflux model is a good tool for examining the causal relationships between GER and respiratory disorders.