Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy.
Purpose: To investigate for the first time the immunohistochemical and mutational status of b-catenin in a mandibular case of adenomatoid odontogenic tumor (AOT) and to review the immunohistochemical expression data of various markers (cytokeratins, metalloproteinases, etc) in such a lesion. Materials and Methods:A case of follicular-type AOT in a young male patient was analyzed in regard to the immunohistochemical expression of b-catenin and mutations of the b-catenin gene (CTNNB1). Its expression is altered in some odontogenic tumors.Results: We found a strong cytoplasmic expression of b-catenin, but no molecular anomaly within the exon 3 of CTNNB1. b-catenin is considered to play a role in cell differentiation processes. Conclusion:Our results were consistent with previous findings in ameloblastoma and malignant odontogenic tumors. However, b-catenin alterations had not been explored in AOT so far. Further studies are necessary to understand the specific regulation of b-catenin in the AOT pathogenesis. Ó
Epstein-Barr virus (EBV), in addition to its transforming properties, contributes to the pathogenesis of several inflammatory diseases. Here, we investigated its involvement in oral lichen planus (OLP), a common autoimmune-like disease of unknown etiopathogenesis that can display a malignant potential. EBV-infected cells (EBV+ cells) were sought in a large series of clinically representative OLPs ( n = 99) through in situ hybridization to detect small noncoding EBV-encoded RNAs. Overall, our results demonstrated that EBV was commonly found in OLP (74%), with significantly higher frequency (83%) in the erosive form than in the reticular/keratinized type mild form (58%). Strikingly, many erosive OLPs were massively infiltrated by large numbers of EBV+ cells, which could represent a large part of the inflammatory infiltrate. Moreover, the number of EBV+ cells in each OLP section significantly correlated with local inflammatory parameters (OLP activity, infiltrate depth, infiltrate density), suggesting a direct relationship between EBV infection and inflammatory status. Finally, we characterized the nature of the infiltrated EBV+ cells by performing detailed immunohistochemistry profiles ( n = 21). Surprisingly, nearly all EBV+ cells detected in OLP lesions were CD138+ plasma cells (PCs) and more rarely CD20+ B cells. The presence of EBV+ PCs in erosive OLP was associated with profound changes in cytokine expression profile; notably, the expression of key inflammatory factors, such as IL1-β and IL8, were specifically increased in OLP heavily infiltrated with EBV+ PCs. Moreover, electron microscopy-based experiments showed that EBV+ PCs actively produced EBV viral particles, suggesting possible amplification of EBV infection within the lesion. Our study thus brings conclusive evidence showing that OLP is commonly infiltrated with EBV+ PCs, adding a further puzzling element to OLP pathogenesis, given that PCs are now considered to be major regulatory immune cells involved in several autoimmune diseases (ClinicalTrials.gov NCT02276573).
The aim of this clinical report is to demonstrate the efficiency of Er:YAG laser in reducing symptoms and lymphoplasmocytic infiltrate in case of oral lichen planus (OLP). In addition to medical therapy and conventional surgery, laser has been proposed for the treatment of this disease, but currently, use of Er:YAG laser (2940 nm) has not been reported. Two clinical cases of female patients who came to our clinic with lesions in the internal portion of the cheek and in the hard palate mucosa close to the upper right molars, surgically treated by Er:YAG laser, are described. The parameters used were as follows: energy, 80-120 mJ; frequency, 6-15 Hz; non-contact hand piece; spot size diameter, 0.9 mm; pulse duration, 100 μsec (VSP) to 300 μsec (SP) ; fluences, 12.6-18.9 J/cm(2); and air/water spray (ratio: 6/5). In the two patients, the peeling of the lesions was completed with much less discomfort (<25% in visual analogue scale). A very small recurrence was observed in one case (cheeks) after 15 months, and the same protocol was applied successfully. The use of this wavelength offers several advantages including, a good and fast healing process, a very low level of discomfort during and after intervention, and a rapid disappearance of symptoms. Even if this methodology seems to be an interesting new surgical approach in the management of non-erosive OLP, this clinical report has to be considered as a preliminary one because of the limited number of cases. As a consequence, further studies and long-term follow-up will be necessary.
Factors of prognosis and radioresistance in oral cavity and pharyngeal squamous cell carcinoma (OCPSCC) are limited. In the present study, the usefulness of tumor DNA content in predicting radioresistance in patients with OCPSCC has been investigated. Radioresistance has been defined as local recurrence or tumor persistence after radiation therapy. DNA-ploidy analysis was performed by static cytometry on smears of cell suspensions obtained from formalin-fixed paraffin-embedded material and stained with Feulgen. DNA-ploidy was correlated with the proliferation rate (Ki-67) and p53 protein accumulation obtained by immunohistochemistry. The follow-up of patients ranged from 8 to 62 months. Radioresistance was more common in non-diploid tumors; 14/28 (50%) non-diploid tumors recurred, whereas only 3 (10.7%) out of 28 diploid tumors had local failure (P=0.0019). Proliferation rate and p53 accumulation, evaluated by immunohistochemistry, also added prognostic information. Twelve out of 14 failures were from non-diploid tumors with a low proliferation rate (Ki-67<20%), whereas none of 20 p53-negative diploid tumors developed recurrences. This study showed that non-diploid tumors responded poorly to radiotherapy. DNA content appeared, therefore, as a significant prognostic marker for the evaluation of OCPSCC in patients receiving radiation therapy. This study also showed that DNA content adds information to p53 accumulation and the proliferation rate (Ki-67) for the purposes of determining patient management.
Objective. The aim of this study was to assess the ability of Er:YAG laser to remove by excision torus mandibularis and to smooth torus palatinus exostosis. Materials and Methods. Torus mandibularis (TM) and torus palatinus (TP) were surgically eliminated via the Er:YAG laser using the following parameters: TM: output power ranging from 500 to 1000 mJ, frequency from 20 to 30 Hz, sapphire tips (diameter 0.8 mm), air-water spray (ratio 5/5), pulse duration 150 μsec, fluence ranging from 99592 J/cm2 to 199044,586 J/cm2. TP: a peeling technique was used to eliminate TP, as excision by slicing being impossible here. Results. TM: excision was obtained after 12730 pulses. TP: smoothing technique took more time compared with excision. Once peeling was considered to be accomplished, the use of a surgical rasp was necessary to eliminate bone spicules that could delay the wound to heal in good conditions. Conclusion. Er:YAG excision (TM) or Er:YAG peeling (TP) are safe clinical techniques easy to practice even if the time required for excision or surface smoothing is more than the time required with bony burs and high speed instruments.
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