Parotid gland ancient schwannoma is an extremely rare entity, with only 6 cases reported to date. Ancient schwannoma present degenerative alteration, including cystic changes, hyalinizing stroma, hemorrhages, infiltration of macrophages, and cellular atypia with hyperchromatic nuclei. These factors have the potential to mimic malignant tumors, resulting in an overestimation of diagnosis and subsequent inappropriate management. In the present case, we report a case of parotid gland ancient schwannoma, which developed relatively fast degenerative alteration without a large-sized mass. We reviewed all the cases of parotid ancient schwannoma, and suggest that the character of parotid gland tissue can deceive the change of tumor growth size. We also suspect that pre-surgical manipulation, such as FNAB or CNB, can cause degenerative changes in a relative short period. It is important to consider reactive degenerative alteration of schwannoma, and not to misinterpret as a malignant entities, notably when needle biopsy history is present.

The limitation of markers for chronic oral diseases such as oral lichen planus (OLP) and burning mouth syndrome (BMS) is a diagnostic challenge for clinicians. The pathogenesis of OLP and BMS is not yet fully understood. Therefore, diagnoses are mainly based on the observation of clinical features and history, rather than established markers. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to determine the state of inflammation; however, these markers have some limitations. Recently, a new inflammatory marker, pentraxin-3 (PTX3), has been identified in other systemic inflammatory diseases. PTX3 is a member of the pentraxin family and is classified as a long pentraxin. PTX3 is found in various human tissues, whereas the classical short pentraxin, CRP, is secreted only in the liver. PTX3 is a marker of autoimmune diseases and periodontitis. However, there are no studies on PTX3 in OLP and BMS; therefore, we sought to determine if PTX3 can be a diagnostic marker for OLP and BMS. PTX3 was found to be correlated with other inflammatory markers, suggesting its diagnostic value for inflammatory oral diseases. We also found that the PTX3 levels were lower in patients with OLP and BMS. ESR levels were elevated in the OLP and BMS groups, but CRP levels were not. Despite these associations, no correlation was found between PTX3 expression and other known clinical features of OLP and BMS. We suggest that PTX3 plays a role in the immunological and neurological pathways involved in the complex pathogenesis of OLP and BMS.

Malignant melanoma is a highly malignant tumor derived from melanocyte. Malignant melanoma of the oral cavity occurs mainly in the palatine mucosa and the maxillary gingiva in men in their 50s. Malignant melanoma can be divided into pigmented and non-pigmented(amelanotic). Among them, non-pigmented malignant melanoma accounts for 2-8% of all malignant melanomas. Pigmented malignant melanoma is detected through changes in pigmentation, whereas non-pigmented malignant melanoma is characterized by no pattern of color change. In this study, at the initial visit, a malignant lesion was suspected and a biopsy was performed. According to the biopsy results, it was diagnosed as polymorphic sarcoma, but the histological examination performed during the operation revealed that it was amelanotic melanoma. As such, the differential diagnosis is important because there is no clinical change in non-pigmented malignant melanoma. Diseases to be differentially diagnosed when non-pigmented malignant melanoma occurs in the oral cavity include squamous cell carcinoma, lymphoma, sarcoma, inflammation, and osteomyelitis. In this study, we report a case that showed the histopathological characteristics of malignant melanoma without superficial pigmentation.

Porphyromonas gingivalis, a major pathogen of chronic periodontitis, colonizes in subgingival crevice and affects surrounding oral tissues, especially in periodontitis patients. Oral cancer mainly occurs in old-aged persons, and are exposed to the P. gingivalis, released from periodontitis, one of the most common inflammatory disease of oral cavity. Thus oral cancer cells may be infected with P. gingivalis, and its biologic behavior are autologously and/or heterogeneously modulated by altering gene expression. Exosomes which are derived from cells contain not only coding genes but also non-coding RNAs such as long non-coding RNAs, miRNA, and piRNAs. Here, to investigate the effect of P. gingivalis on oral cancer cells and to gain insight into the crosstalk between inflammatory signal from tumor microenvironment and oral cancer, we observed miRNA profiles of exosomes from P. gingivalis–infected oral cancer cells. Upregulation of 6 miRNAs, miR-203-3p, miR-6516-3p, miR-483-5p, miR-1275, miR-8485, and miR-19a-3p, were observed whereas 14 miRNAs including let-7a-3p, miR-106a-5p were downregulated. In addition, KEGG pathway analysis using the upregulated- and downregulated- miRNAs showed association with cell adhesion molecules pathway and ECM-receptor interaction pathway, respectively. These findings suggest that P. gingivalis could modulate biologic behavior of oral cancer cells through changes of exosomal miRNAs.

Hypoxia is one of the most common features of cancer. It is also associated with cancer progression and the acquisition of aggressiveness, which includes invasion and metastasis. Oral squamous cell carcinoma accounts for 90% of all oral cancers, and its 5-year survival rate is about 50%. Despite various attempts and trials, its prognosis has not improved. Among numerous adverse prognostic factors, hypoxia is suspected as one of the most important factors, as it increases the aggressiveness of oral cancer cells. We attempted to observe the effect of hypoxia on the expression of epithelial-mesenchymal transition markers in oral cancer cells. We analyzed and compared both the mRNA and protein expression levels of epithelial-mesenchymal markers using qRT-PCR and western blotting in both normoxic and hypoxic YD10B oral squamous cell carcinoma cells. Eighty-six genes were analyzed through real-time PCR using commercial microarray plates, performed in triplicate. Among the 86 genes, the expression of 24 were increased (≥ 2 fold) by hypoxia, while that of three genes was decreased (≥ 2 fold). Hypoxia significantly affects epithelial-mesenchymal transition-related genes. Further studies on the regulation of these genes may help to develop more efficient therapeutic modalities for oral cancer and to improve prognosis of oral cancer patients.

Squamous odontogenic tumor (SOT) is a relatively rare, benign, small (rarely > 1.5 cm in diameter), but locally infiltrative and occasionally aggressive odontogenic epithelial lesion that appears to have harmatomous and neoplastic characteristics [1]. SOT is often asymptomatic, although it can present with mildly painful gingival swelling or tooth mobility. Radiographically, SOT is usually visualized as an irregularly or triangularly shaped unilocular radiolucency associated with the lateral roots of teeth. We report a case of the squamous odontogenic tumor occurring in a 60-year-old female in the right posterior maxilla with unusual radiographic and clinical appearances.

MicroRNAs (miRNAs) are a group of small non-coding RNAs consisting of 18~24 nucleotides in length. Each miRNA is expected to bind a few hundreds of putative target mRNAs, thus inhibiting their translation into protein products mostly by degradation of targets. With its biogenesis extensively deciphered, miRNAs have been implicated in a variety of biological processes, including early development and cellular metabolism. In addition, dysregulation of miRNAs and subsequent alterations in the expression of its target molecules are thought to be linked to the pathophysiology of multiple human illnesses, including cancer. To establish the miRNA-target relationships important for developing a specific disease, it is critical to validate the putative targets of each miRNA suggested by computational methods in vivo. In this review, we will first discuss oncogenic and tumor-suppressive roles of miRNAs in human cancer and introduce computational methods to predict putative targets of miRNAs. Then, the value of Drosophila melanogaster as an alternative model system will be further discussed in studying human cancer and in validating the miRNA-target relationships in vivo. Finally, we will present a possibility of applying the mammals-to-Drosophila-to-mammals approach to study the roles of miRNAs and their targets in the pathophysiology of oral cancer, an intractable type of cancer with poor prognosis and survival rate.

Recently chronic inflammation is focused on the association with cancer progression and acquisition of aggressive biologic behaviors, such as invasion, metastasis, and resistance to chemotherapeutic reagents. Due to the close vicinity within oral cavity, oral cancer may be intimately associated with chronic periodontitis. The present study was done to observe the effect of chronic periodontitis on oral cancer cells by utilizing P. gingivalis infection, a major pathogen in chronic periodontitis. We analyzed and compared the mRNA expression levels of epithelial-mesenchymal transition (EMT) markers in non-infected and P. gingivalis-infected oral cancer cells. Eighty-six genes, which are well known as EMT markers, were analyzed using commercially available EMT microarray plates, performed in triplicate. Among the 86 genes, the expression of 26 was increased (≥ 2 fold) by P. gingivalis, whereas that of 7 genes was decreased (≥ 2 fold). Our study suggests that P. gingivalis infection evokes significant changes in EMT-related genes. Further observations on molecular mechanisms underlying these changes may help to clarify the role of chronic periodontitis on cancer progression and to develop more efficient preventive and therapeutic modalities for oral cancer. (182 words)

Porphyromonas gingivalis is a gram-negative bacteria of rod shape, and grown in an anerobic condition. It colonizes in subgingival crevice and is known as a major pathogen causing chronic periodontitis. It possesses an invasive property and replicative potential within various cell types, presumably playing an important role in modulating biological behaviors of oral cancer. However, the pathophysiology of P. gingivalis in the malignant transformation of oral cancer has not been fully understood. In this study, we aimed to investigate molecular changes of oral squamous cell carcinoma cells induced by repetitive P. gingivalis infection that clinically resembles chronic periodontitis.

Recently, the importance of inflammation in carcinogenesis has been recognized and studied extensively. As a result, a clear correlation between inflammation and carcinogenesis has been well established in some types of cancers. Despite a high prevalence of chronic periodontitis, one of the most common inflammatory diseases in the general population, there are only a few reports on the role of chronic periodontitis in oral cancer progression. In this study, we aimed to investigate genetic changes in oral cancer cells induced by repetitive Porphryomonas gingivalis infections to mimic chronic periodontitis in a clinical setting. Cells of oral squamous cell carcinoma (OSCC), the most common type of oral cancer, and P. gingivalis 381 were used for the present study. ID1 and ID3 were mRNAs of higher expression in the P. gingivalis-infected group compared to the uninfected control. These mRNAs have been regarded as important modulators participating in cancer progression. Future studies will provide an insight into the roles of the molecules we identified in oral cancer progression. Outcomes from these studies will also shed light on the significance of chronic periodontitis induced by bacterial pathogen, such as P. gingivalis, in progression of oral cancer and relevant molecular mechanisms underlying altered cancer cell behaviors.

Chronic inflammation has long been considered as an important contributing factor to the development of malignant tumors in various tissues. In this study, we aimed to investigate a potential association between chronic periodontitis, a representative inflammatory disease in the oral cavity, and oral squamous cell carcinoma (OSCC), the most common form of malignant tumors in the oral cavity. A retrospective study was designed to include the cases and controls, each of which consisted of patients first diagnosed with OSCC and temporomandibular disorders, respectively. The existence or a history of periodontal disease was quantitatively estimated based upon the level of alveolar bone loss (ABL) from panoramic radiographs in these groups. Unlike other covariates, including LDH, WBC count and hemoglobin, the levels of ABL measured at three independent regions (second premolar and first/second molar) were significantly higher in the OSCC group, regardless of the patients’age in most cases. Our results thus support the hypothesis that chronic periodontitis, represented by significant ABL, is an important and clinically relevant factor potentially associated with the development of OSCC.

Chronic inflammation is widely considered to predispose individuals to cancer. Microorganisms facilitate recruitment and activation of inflammatory cells and thus allow release of inflammatory mediators. These molecules can then promote accumulation of mutations, leading to tumor development in the host. Porphyromonas gingivalis, a pathogen causing chronic periodontitis, is detected in oral squamous cell carcinoma (OSCC) tissues. Considering a strong link between chronic inflammation and tumor development, functional consequences of P. gingivalis infection may include malignant transformation of the host cells. In this study, we monitored transcriptional changes induced by invasion of P. gingivalis in OSCC cells using microarrays. Our preliminary results suggest changes in a wide range of genes involved in inflammation, apoptosis and autophagy, tumor progression, and carcinogenesis. Further studies on molecular mechanisms underlying these changes will lay a useful foundation to elucidate the role of microorganism-related inflammation and for the development of preventive and therapeutic agents for oral cancer.

Metastasis consists of complex cascades and a lot of factors are involved in each step of metastasis. In recent studies, the role of epithelial-mesenchymal transition (EMT) in metastasis is suggested. EMT has a feature of epithelial cells conversing into mesenchymal cells morphologically and phenotypically, is a characteristic of malignant and metastatic cells in most cancer. The mesenchymal cells usually show more malignant phenotype, including invasion and metastasis. EMT can play an important role in metastasis of oral squamous cell carcinoma (OSCC). Although the role of Snail, slug, other transcriptional factors and E-cadherin are well known in human cancers, there are a few studies on N-cadherin and Twist expression in OSCC. The present study was aimed to analyze the expression of N-cadherin and Twist protein in OSCC from Korean patients. The immunohistochemical stain was performed using 58 primary OSCCs and 6 metastatic OSCCs, and the correlation between the expression of these proteins and clinicopathological parameters of OSCC patients was analyzed. The expression rate of high expression of N-cadherin was observed in 70.4% and Twist in 87.3% of OSCC. The expression of N-cadherin in metastatic OSCC increased than in corresponding primary OSCC (p<0.05). The spearman correlation coefficiency between N-cadherin and Twist was calculated as 0.228. The clinical factors such as lymph node metastasis and survival showed statistically significant correlation between N-cadherin expression. The expression of Twist was correlated with recurrence. In conclusion, the authors suggest that N-cadherin may play an important role in malignant behaviour of OSCC and can be considered as prognostic indicator of OSCC.

Runt-related transcription factor (RUNX) 3 is well known as a developmental regulators, as well as candidate tumor suppressor gene in human breast cancer, gastric cancer, esophageal cancer, and so on. The present study was aimed to analyze the expression of RUNX3 protein in oral squamous cell carcinoma (OSCC) from Korean patients. The immunohistochemical stain was performed with 14 normal oral mucosa (NOM) and 25 OSCCs, and statistical analysis was carried out to find out the correlation between the expression of RUNX and clinicopathological parameters of OSCC patients. In OSCC, the expression of RUNX3 protein was found to increase more than in NOM. Moreover, in the univariate correlation analysis, the gender, regional lymph node metastasis, and histopathologic differentiation of OSCC patients were positively correlated with the expression of RUNX3 (p<0.05). These results indicate that RUNX3 can play a role as an oncogene in OSCC, in contrast to some reports on RUNX3 in other human cancers. In addition, RUNX3 may be considered as new malignant biomarker of OSCC.

Cancer cells are often found in an ischemic condition due to the rapid outgrowth of their vascular supply, and these cells are expected to develop an increased potential for local invasive growth. Since the first steps are characterized by increased motility and invasiveness, expression of molecules involved in cellular adhesion to extracellular matrix (ECM) is increased in the process of cancer cell invasion and metastasis. In this work we explored the molecular characteristics and its regulatory mechanism of hypoxic oral squamous cell carcinoma (OSCC) cells. Our experiment identified that hypoxia increases α5 integrin protein levels through phosphoinositide 3-kinase (PI3K)/Akt pathway in OSCC cells.