Thymosin ß4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma.

The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin ß4 (Tß4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tß4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tß4-overexpressing OSCCs, SCC-15_Tß4 and SCC-25_Tß4, enhanced cell proliferation and colony formation. In addition, we observed that Tß4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tß4 and SCC-25_Tß4 cells. Tß4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tß4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tß4 molecule would encourage the development of specific targets for cancer treatment.

The role of p300 in the tumor progression of oral squamous cell carcinoma.

BACKGROUND: EP300 gene encoding p300 is a candidate tumor suppressor gene. This study investigated p300 expression and gene alteration in oral squamous cell carcinoma (OSCC) specimens to assess its role in OSCC development. METHODS: Genomic DNA extracted from 13 human OSCC cell lines and 40 OSCC patient specimens was subjected to methylation-specific PCR and exon sequencing. Immunohistochemical staining with primary antibodies against p300 and p53 was performed in 48 patients with OSCC. We analyzed the association between the data and clinicopathological factors of OSCC patients. RESULTS: Methylation-specific PCR revealed that the EP300 promoter region was not hypermethylated in OSCC. Only one cell line demonstrated a point mutation at exon 31. On immunohistochemical examination, patients with metastatic lymph nodes (P = 0.009) and advanced clinical stage (P = 0.046) tended to show increased expression of p300. There was no statistically significant relationship between p300 expression and p53 accumulation in OSCC tissue samples. Patient survival was not correlated with p300 expression. CONCLUSIONS: EP300 is not a tumor suppressor gene because there was neither epigenetic inactivation of the gene nor a mutation resulting in functional impairment. Based on p300 overexpression and its association with clinical factors in patients with OSCC, it is likely that p300 itself or one of its target genes plays a key role in the aggressive phenotypes of OSCC.

The potential of interleukin 12 receptor beta 2 (IL12RB2) and tumor necrosis factor receptor superfamily member 8 (TNFRSF8) gene as diagnostic biomarkers of oral lichen planus (OLP).

OBJECTIVE: This study evaluated the potential of interleukin 12 receptor beta 2 and tumor necrosis factor receptor superfamily member 8 as diagnostic biomarkers of oral lichen planus (OLP). MATERIALS AND METHODS: The mRNA expression of IL12RB2 and TNFRSF8 in FFPE OLP samples (OLP group, n = 38) were investigated with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and compared to those of chronic non-specific mucositis (Non-OLP group, n = 25) and normal mucosa (Normal group, n = 18). Predictive modeling of the expression of IL12RB2 and TNFRSF8 was constructed using support vector machine (SVM), random forest (RF), linear discriminant analysis (LDA), neural network (NN) and naive Bayes (NB) methods. RESULTS: Normalized expression of IL12RB2 in the OLP group (3.78 ± 1.67) was significantly higher than the Normal group (1.97 ± 1.12), but lower than the Non-OLP group (6.86 ± 1.67). TNFRSF8 gene expression in the OLP group (7.46 ± 1.51) was significantly higher than the Normal group (2.90 ± 1.61), but no significant difference was found between the OLP and Non-OLP groups. The ratio of IL12RB2/TNFRSF8 in the OLP group (0.52 ± 0.23) was significantly lower than the Normal group (0.74 ± 0.39) and the Non-OLP group (1.07 ± 0.38). In the predictive modeling, the area under receiver operating characteristic (ROC) curves (AUC) ranged from 0.83-0.92 and their accuracy was higher than 0.75 in all methods. CONCLUSIONS: The IL12RB2/TNFRSF8 ratio can be a useful diagnostic tool for OLP.

Multiple calcifying hyperplastic dental follicles: comparison with hyperplastic dental follicles.

BACKGROUND: Multiple calcifying hyperplastic dental follicles (MCHDF) is a rare disorder that is characterized by multiple impacted teeth and enlarged dental follicles that include calcifications. The current lack of information characterizing MCHDF impedes clinicians from making prompt differential diagnoses. We describe five cases of MCHDF and analyze their clinical and histopathological features in an effort to compare MCHDF with hyperplastic dental follicles (HDF) of singly impacted teeth. METHODS: Our five cases of MCHDF were examined and clinically/histologically compared with data from 50 singly impacted teeth with HDFs. RESULTS: The five patients described in this study were all male. The pattern of impaction varied, but every second molar was impacted in all the patients. Alterations in the number of teeth, such as supernumerary or congenitally missing teeth were observed. Upon microscopic examination, most of the calcifications consisted of basophilic droplets that were fused to one another, and were surrounded by whirling spindle cells. Another type of calcification that was observed less frequently resembled woven bone. These features were consistent with three previously reported cases and observed in HDFs of 20 singly impacted teeth. While the average period of impaction and the time to reach some level of calcification in MCHDFs was shorter than in single calcifying HDFs, the calcification was more generalized in MCHDFs. CONCLUSIONS: This study indicates that MCHDF is a separate pathologic entity with exclusive male predilection and earlier calcifications, different to HDF. Further studies are needed to understand the etiology of MCHDFs to provide various options for treatment, and to clarify the mechanisms of eruption.

Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma.

BACKGROUND: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. METHODS: To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan-Meier's test. RESULTS: Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. CONCLUSIONS: These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.

CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells.

BACKGROUND: Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells. METHODS: We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples. RESULTS: CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells (P < 0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells (P < 0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples. CONCLUSION: These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.

The change in dimension of the masseter muscle in rabbits after radiofrequency therapy.

PURPOSE: The objective of this study was to evaluate the change in muscle dimension after administering radiofrequency (RF) therapy. MATERIALS AND METHODS: This study used 6 male New Zealand rabbits. Groups were divided by number of applications of RF (eg, 1 to 4 points). The dimension of the masseter muscle was measured using a computerized tomogram scan before operation, and at 1, 2, 3, and 4 weeks after RF therapy was administered under the same conditions. Two horizontal cuts were selected for measurement. RESULTS: The size of the measured areas for each group at 1 week after RF therapy was significantly increased compared with the preoperative value (P< .05). When the measurements of each group at 3 and 4 weeks after RF therapy were compared with the preoperative value, they were significantly decreased (P< .05). The dimensional change was significantly different among groups at 1 and 3 weeks post RF therapy (P< .05). The swelling at 1 week after RF therapy was increased in terms of the number of RF applications. The ratio of dimension was decreased at 3 weeks after RF therapy in terms of the number of RF applications. CONCLUSION: There was an increase in muscle dimension because of swelling in the early stages of RF therapy. However, this dimension decreased at 3 weeks post-RF administration compared with the preoperative value. Therefore, it can be concluded that the change in the masseter muscle dimension was dependent on the number of RF applications.

Accelerated biodegradation of silk sutures through matrix metalloproteinase activation by incorporating 4-hexylresorcinol.

Silk suture material is primarily composed of silk fibroin and regarded as a non-resorbable material. It is slowly degraded by proteolysis when it is implanted into the body. 4-Hexylresorcinol (4HR) is a well-known antiseptic. In this study, the biodegradability of 4HR-incorporated silk sutures were compared to that of untreated silk sutures and polyglactin 910 sutures, a commercially available resorbable suture. 4HR-incorporated silk sutures exhibited anti-microbial properties. Matrix metalloproteinase (MMP) can digest a wide spectrum of proteins. 4HR increased MMP-2, -3, and -9 expression in RAW264.7 cells. MMP-2, -3, and -9 were able to digest not only silk fibroin but also silk sutures. Consequently, 59.5% of the 4HR-incorporated silk suture material remained at 11 weeks after grafting, which was similar to that of polyglactin 910 degradation (56.4% remained). The residual amount of bare silk suture material at 11 weeks after grafting was 91.5%. The expression levels of MMP-2, -3 and -9 were high in the 4HR-incorporated silk suture-implanted site 12 weeks after implantation. In conclusion, 4HR-treated silk sutures exhibited anti-microbial properties and a similar level of bio-degradation to polyglactin 910 sutures and induced higher expression of MMP-2, -3, and -9 in macrophages.

Staging significance of bone invasion in small-sized (4cm or less) oral squamous cell carcinoma as defined by the American Joint Committee on Cancer.

OBJECTIVES: The staging significance of bone invasion is controversial in oral squamous cell carcinoma (OSCC) cases with tumors measuring 4cm or less according to the American Joint Committee on Cancer (AJCC). Our aim was to retrospectively examine a large group of patients with OSCC to determine the staging significance of bone invasion. MATERIALS AND METHODS: Three hundred and twenty-three patients with primary OSCC were classified based on tumor size. Bone invasion was categorized as absent, one side bone, and both buccal and lingual bones, and analyzed for association with disease progression. Regional lymph node metastasis (N), perineural invasion, vascular invasion, surgical margin involvement, and adjuvant treatment were also analyzed. RESULTS: In all OSCC cases, bone invasion (p=0.007) with stage N, perineural invasion, and surgical margin involvement were significant independent prognostic factors of disease progression. However, in OSCC cases with tumors measuring 4cm or less, bone invasion was not significantly associated with disease progression. Nevertheless, invasion of both buccal and lingual bones was significantly associated with disease progression (p=0.03). In multivariate analysis, both buccal and lingual bone invasion (p=0.04; hazard ratio=3.4; 95% confidence interval, 1.0-11.0), stage N2, and perineural invasion were also independent prognostic factors. CONCLUSION: Although OSCC bone invasion was an independent prognostic factor, bone invasion in small OSCC was not. However, small OSCC with both buccal and lingual bone invasion had a significantly worse prognosis. The AJCC T system is of limited prognostic value for small OSCC with bone invasion. But other elements should be examined before a modification can be accepted.

Chondrosarcoma of the temporomandibular joint: a case report and review of the literature.

OBJECTIVE: Chondrosarcoma is the second most common sarcoma arising in the bone, but it rarely involves the temporomandibular joint (TMJ). To date, 30 cases of TMJ chondrosarcoma have been reported in the English literature, and the authors report an additional case arising from a cystic lesion in a 60-year-old female patient. CLINICAL PRESENTATION: The clinical and radiological diagnosis of the lesion was initially synovial cyst, and periodic check-ups were done after aspiration of the lesion. After three years, the patient perceived swelling of the lesion, and surgical excision was performed. The final diagnosis was grade I chondrosarcoma. CONCLUSION: When clinicians detect a cystic lesion in the radiographic imaging of the TMJ, chondrosarcoma should be included in the differential diagnosis. In addition, computed tomography (CT) as well as magnetic resonance imaging (MRI) is recommended for the accurate diagnosis and proper preoperative planning in TMJ chondrosarcoma.

Atypical granular cell tumor in the maxilla: The first report of primary intraosseous granular cell tumor.

BACKGROUND: Granular cell tumor (GCT) is a benign soft tissue tumor of neural origin and is characterized by eosinophilic granular cells showing positivity for neuronal markers. Herein, we report the first case of primary intraosseous GCT arising in the maxilla of an adolescent girl. METHODS AND RESULTS: A 16-year-old female patient presented with palatal swelling. Radiographic findings revealed a well-defined radiolucent lesion centrally located in the right maxilla. Mass excision was performed, and histopathologic examination showed sheets and cords of eosinophilic granular cells with cellular pleomorphism. Tumor cells were strongly positive for vimentin, S-100 protein, and CD56, and negative for cytokeratin, desmin, smooth muscle actin, and c-kit. High expression of p53 and Ki-67 was found. The final diagnosis was atypical GCT. CONCLUSION: When evaluating an intraosseous radiolucent lesion with histopathologic features of granular cells, clinicians and pathologists should include GCT in the differential diagnosis. © 2016 Wiley Periodicals, Inc. Head Neck 38:E2467-E2470, 2016.

Prognostic significance of nestin in primary malignant melanoma of the oral cavity.

Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.

KiSS-1 expression in oral squamous cell carcinoma and its prognostic significance.

Downregulated expression of KiSS-1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS-1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS-1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS-1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS-1. Correlations between KiSS-1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS-1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan-Meier survival analysis, negative KiSS-1 expression significantly correlated with poorer overall survival (OS) and disease-free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS-1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS-1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC.

Geriatric oral lesions: A multicentric study.

AIM: To carry out an oral biopsy survey in geriatric patients from the participating institutions. METHODS: The biopsy records of the participating institutions were reviewed for oral lesions from patients aged 65 years and older diagnosed from 2003 to 2012. Demographic data and the site of the lesions were collected. Histopathological diagnoses were categorized into two categories: non-neoplastic lesions (reactive/inflammatory lesion, cyst, allergic/immunologic disorders, potentially malignant disorders, infection and others) and neoplastic lesions (benign and malignant tumors). Data were analyzed by appropriate statistics using stata11. RESULTS: Of the 76,045 accessioned cases, 11,346 cases (14.92%) were in geriatric patients. The mean age of the patients was 72.98 ± 6.25 years. A total of 5010 cases (44.16%) were diagnosed in males, whereas 6336 cases (55.84%) were diagnosed in females. The male-to-female ratio was 0.79:1. Non-neoplastic lesions outnumbered the neoplastic counterpart. The five most prevalent oral lesions in the geriatric population in the present study in descending order of frequency were squamous cell carcinoma, focal fibrous hyperplasia (irritation fibroma), radicular cyst, osteomyelitis and epithelial dysplasia, respectively. The site of predilection was labial/buccal mucosa, followed by gingiva, mandibular bone, tongue and maxillary bone, respectively. CONCLUSIONS: The geriatric oral lesions from the present study showed a similar trend with studies based on histopathological data, but different from the studies based on clinical data. This study also shed more light on potentially malignant disorders, as well as benign and malignant tumors.

Hematogenous infection of the human temporomandibular joint.

Objective This study was designed to discover the relationship between bacteremia and the presence of specific bacterial species in the synovial fluid of the human temporomandibular joint (TMJ). Study design Sixteen volunteers (female to male, 1:2.2; average age, 30.00 +/- 9.93 years) who received operations via intraoral incision participated in this study. Samples from the blood and TMJ synovial fluid of the patients were taken preoperatively and postoperatively and analyzed by PCR assays with specific primers for the clinically important bacteria Staphylococcus aureus , Streptococcus mitis , and beta-hemolytic Streptococcus . Results PCR-based assays revealed the occurrence of S aureus in 68.8% and 50% of the total blood and synovial fluid samples collected immediately after the operations, which statistically differed from the preoperative samples ( P < .05). However, the frequency of the other bacteria, S mitis and beta-hemolytic Streptococcus , in pre- and postoperative blood samples had no such a difference ( P > .05). The chi-square test showed a significant association between the presence of S aureus in the blood and in TMJ synovial fluid (chi 2 = 6.409, P < .05), and the probability of hematogenous infection of the TMJ was estimated as 55.5%. Conclusion Hence, the data obtained provided evidence that the invasion of S aureus into TMJ synovial fluid was due to the presence of these bacteria in the blood. To our knowledge, this is the first report of the bacteremia-related mechanism of S aureus invasion in the human TMJ.

The Effect of a Combination of Implant Controller and Handpiece from Different Manufacturers on the Torque Value.

PURPOSE: To determine the accuracy of applied torque of different implant controller and handpiece combinations by using an electronic torque gauge. MATERIALS AND METHODS: Four combinations of the following devices were tested: Surgic XT controller (NSK), XIP10 controller (Saeshin), X-SG20L handpiece (NSK), CRB26LX handpiece (Saeshin). For five torque settings, 30 measurements were recorded at 30 revolutions per minute by using an electronic torque gauge fixed to jigs, and means were calculated. RESULTS: Applied torques were generally higher than the set torque of 10 and 20 Ncm and lower than the set values of 40 and 50 Ncm. The average torque deviations differed significantly among the combinations (P < .05). At 10 and 20 Ncm, the Surgic XT/X-SG20L combination yielded the closest value to the intended torque, followed by the XIP10/X-SG20L combination. At 30 Ncm, the XIP10/X-SG20L combination showed the nearest value. At 40 Ncm, the Surgic XT/X-SG20L, XIP10/CRB26LX, and XIP10/X-SG20L combinations showed deviations within 10%. At 50 Ncm, all the combinations showed lower applied torque than the set value. Large standard deviations were observed in the Surgic XT/CRB26LX (13.288) and Surgic XT/X-SG20L (7.858) combinations. CONCLUSION: Different combinations of implant controllers and handpieces do not generate significant variations in applied torque. The actual torque varies according to the torque setting. It is necessary to calibrate devices before use to reduce potentially problematic torque.

Expression of membrane type I-matrix metalloproteinase in oral squamous cell carcinoma.

A local invasion and lymph node metastasis (LNM) of an oral squamous cell carcinoma (OSCC) has a poor prognosis, and involves the degradation of the extracellular matrix mediated by multiple proteolytic enzymes including membrane type I-matrix metalloproteinase (MT1-MMP). This study aimed to determine the role of MT1-MMP in OSCC, to evaluate the immunohistochemical expression of MT1-MMP with regard to the invasiveness and LNM of the OSCC, and to evaluate the major source of MT1-MMP mRNA and its protein using immunohistochemistry and in situ hybridization. MT1-MMP expression was examined in 46 OSCCs via immunohistochemistry and non-radioisotope in situ hybridization. The relationship between MT1-MMP expression and LNM, as well as the histological invasiveness, was statistically analyzed. The results showed that whereas 12 out of the 18 OSCCs (66.7%) with LNM showed moderate to strong MT1-MMP expression, only nine of the 28 OSCCs (32.1%) without LNM expressed MT1-MMP strongly. MT1-MMP expression was significantly higher with regard to LNM (P=0.022). As the invasion grade became stronger (from grade a to grade d), MT1-MMP was significantly more strongly expressed (P=0.033). These results suggest that MT1-MMP is primarily secreted in the OSCC cells and is involved in the invasiveness of the OSCC and LNM. Moreover, MT1-MMP combined with other markers may be used to predict the metastatic potential of an OSCC.

Inactivation patterns of p16/INK4A in oral squamous cell carcinomas.

The p16/INK4A is one of the major target genes in carcinogenesis and its inactivation has frequently been reported in other types of tumors. The purpose of this study is to evaluate inactivation patterns of p16/INK4A in oral squamous cell carcinoma. Six different oral cancer cell lines, SCC-4, SCC-9, SCC-15, SCC-25, KB, and SNUDH- 379 were examined for inactivation of p16/INK4A genes. In the analysis of p16/INK4A gene inactivation, PCR amplification, direct sequencing, and methylation-specific PCR methods were adopted for evaluation of homozygous deletion, point mutation, and promoter hypermethylation, respectively. Homozygous deletion was detected in SCC-25 and SCC-9. SCC-15 showed hypermethylated promoter region within p16/INK4A gene. It is suggestive in the present study that inactivation patterns of p16/INK4A were mainly homozygous deletion, promoter methylation rather than point mutation in oral squamous cancer cell lines, so treatment modalities of oral squamous cell carcinoma should be focused on these types of inactivation.

Plasmablastic lymphoma of the oral cavity in a human immunodeficiency virus-negative patient: a case report with literature review.

Plasmablastic lymphoma (PBL) is an aggressive diffuse large B-cell lymphoma variant that is most frequently observed in the oral cavity of human immunodeficiency virus (HIV)-infected individuals. However, in recent years, some cases have emerged in patients without HIV infection and involve other sites like stomach, lung, nasal cavity, and jejunum. We report a rare case of PBL in the maxillary anterior area of a 62-year-old man without HIV infection. The tumor cells were characterized by non-cohesive round or oval shape cells with eccentrically-placed nuclei with a prominent perinuclear halo. Immunohistochemical studies showed that the tumor cells were strongly positive for MUM1, VS38c, VMT, and κ light chain, focally positive for LCA and CD79a, and negative for CD3, CD20, CD56, λ light chain, CK-pan, EMA, and HMB45. The patient was treated with chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisone. The lesion showed partial remission.

Hypothetical pathogenesis of eosinophilic infiltration in Langerhans cell histiocytosis of the jaw.

OBJECTIVE: The present study investigated the densities of mast cells and CCL-11/eotaxin-1 expression of tumor cells in Langerhans cell histiocytosis (LCH) of the jaw. STUDY DESIGN: Eleven LCH cases arising in the jaws were selected. We evaluated eotaxin-1 expression in LCH cells via immunohistochemical staining. Toluidine blue was used to stain mast cells, with 20 periapical granuloma specimens serving as the control group. RESULTS: In all 7 patients with multifocal LCH, jaw lesions were the earliest manifestation. Toluidine blue staining revealed that most of the mast cells involved in LCH were degranulated, and the number of mast cells in LCH lesions was not significantly higher than in periapical granulomas. Upon immunohistochemical examination, all patients but one showed positivity for eotaxin-1 in LCH cells. CONCLUSION: This preliminary study suggests that eotaxin-1 expression in LCH cells may contribute to eosinophilic infiltration. Further studies of chemokine-receptor interactions will be needed to confirm this.