Multinucleated giant cells appear in a variety forms in different types of oral lesion. However, their nature is still not well understood. Thus, to address this issue, the immunohistochemical characteristics of inflammatory giant cells (Langhans’ giant cells in lesions of tuberculosis and foreign body giant cells in odontogenic keratocysts and squamous cell carcinomas) and tumor giant cells in central giant cell granulomas were compared with those of osteoclasts, the normal giant cell, using a panel of macrophage and osteoclast marker antibodies, such as calcitonin receptor (CT-R), c-Src, Cathepsin K (Cath-K), CD14, RANK, and c-fms. The foreign body giant cells around cholesterol clefts in inflamed odontogenic keratocysts revealed more macrophage-like characteristics than the foreign body giant cells resorbing keratin pearls in squamous cell carcinomas. As such, both cases of foreign body giant cell exhibited immunoreactivity for the macrophage markers, such as CD14, RANK, and c-fms, yet only the latter case exhibited immunoreactivity for the osteoclast markers, such as CT-R and c-Src. Moreover, both cases of foreign body giant cells were positive for TRAP activity, yet negative for Cathepsin K activity. In contrast, the other inflammatory giant cells, Langhans’ giant cells, exhibited immunoreactivity for both the macrophage and osteoclast markers, yet were negative for TRAP activity. Meanwhile, the giant cells in the central giant cell granulomas reacted positively to both the macrophage and osteoclast markers, and were also positive for TRAP activity. Accordingly, these findings suggest that the immunoprofiles of giant cells in oral lesions vary according to the nature of the lesion, despite shared osteoclast and macrophage characteristics. Furthermore, the giant cells in tumorous lesions closely associated with bony destruction revealed more osteoclastic characteristics and their enzyme components were different according to the nature of the lesion

The tumor suppressor gene, phosphate and tensin homologue(PTEN) has been shown to dephosphorylate the phosphatidylinositol 3-kinase(PI 3-K)-generated phosphatidylinositol(3-5)-triphosphate in vivo, thus interfering with the potentially oncogenic signals emanating from PI 3-K. Promoter hypermethylation of CpG islands has recently been shown to be an epigenetic change resulting in loss of function in some genes involved in cell cycle regulation and DNA repair. Immunohistochemal staining for monoclonal antibody 6H2.1 was performed from paraffin embedded blocks of 20 benign epithelial lesions and 40 head and neck squamous cell carcinomas(HNSCCs). Immunoreactivity was graded semiquantitatively by considering the percentage and intensity of the staining of the tumor cells. Also, this study tried to identify PTEN methylation in benign epithelial lesions(24 cases) and HNSCCs(44 cases of paraffin embedded blocks, 4 cases of frozen tissues) using methylation-specific PCR(MSP). In HNSCCs, immunoreactive scores of stage 1 and 2(12 cases, average score 85.2) were higher than those of stage 3 and 4(15 cases, 41.9) and statistically significant(P=0.017). Immunoreactive scores of moderate and poorly differentiated carcinomas(22 cases, 61.6) are more or less lower than those of well differentiated carcinoma(15 cases, 87.0) but not significant(P=0.361). Among 24 cases of benign epithelial lesions, 12 cases showed unmethylated PTEN but none methylated. In HNSCCs, 22 of 44 paraffin embedded blocks showed unmethylated PTEN but none methylated, and all 4 frozen tissue revealed unmethylated PTEN, one of which(25%) methylated. We consider that the loss of PTEN protein expression may be associated with the progression of HNSCCs and the other alteration rather than methylation may be important in the inactivation of PTEN in HNSCCs.

Expression of invasion/metastasis suppressor, E-cadherin, is reduced in many types of human carcinomas. Although somatic and germline mutations in the CDH1, which encodes the human E-cadherin, have frequently been reported in cases with diffuse gastric and lobular breast cancers, irreversible genetic inactivations are rare in other human carcinomas. Recently, it has been well documented that some genes in human cancers may be inactivated by altered CpG methylation. Herein, we determined the expression and methylation status of E-cadherin in oral squamous cell carcinoma(SCC) by immunohistochemistry and methylation-specific PCR. The expression of E-cadherin was significantly higher in the well-differentiated oral SCCs than the moderately or poorly differentiated ones. None of eight tested benign epithelial hyperplasias showed aberrant methylation, whereas five of 12 oral squamous cell carcinomas showed aberrant methylation. When we compared E-cadherin expression with methylation status, oral SCCs with normal methylation showed a higher expression of E-cadherin than those with methylation. These findings suggest that aberrant CpG methylation of CDH1 promoter region is closely associated with transcriptional inactivation and might be involved in tumor progression of the oral mucosa.

Amino acid transporters play an important role in supplying organic nutrient to cells. The expression of L-type arnino acid transporter 1 (LATl) and its subunit 4F2 heavy chain (4F2hc) was evaluated to deterrnine the alterations to these transporters in oral norrnal mucosa (ONM) , oral precancerous lesion (OPL) and oral squamous cell carcinoma (OSCC). Sections from formalin-ftxed, paraffm-embedded S따nples of ONM, OPL or OSCC were exarnined using immunohistochernical staining to detect LATl and 4F2hc proteins. 까le LATl and 4F강lC expression increased progressively from ONM to hypeφ，Iastic and to dysplastic lesions and OSCC. In partiαlar， LATl rnay be a more S야dftc indicator of tumor prog~않sion than 4F2hc. 까le gradually increasing LA Tl and 4F2hc expression detected during the multistep progressive change shows that the protein rnay have an important role in the early stages of multistep oral carcinogenesis. In addition, the specific inhibition of LA Tl and 4F2hc rnight be a new rationale to suppress oral cancer progression.