Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis.

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, ELMO2 and TBC1D2B, have been linked to Ramon syndrome. The objective of this study was to further investigate the genetic variants associated with Ramon syndrome as well as HGF. Clinical, radiographic, histological, and immunohistochemical examinations were performed on affected individuals. Exome sequencing identified rare variants in TBC1D2B in both conditions: a novel homozygous variant (c.1879_1880del, p.Glu627LysfsTer61) in a Thai patient with Ramon syndrome and a rare heterozygous variant (c.2471A>G, p.Tyr824Cys) in a Cambodian family with HGF. A novel variant (c.892C>T, p.Arg298Cys) in KREMEN2 was also identified in the individuals with HGF. With support from mutant protein modeling, our data suggest that TBC1D2B variants contribute to both Ramon syndrome and HGF, although variants in additional genes might also contribute to the pathogenesis of HGF.

Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma.

Objectives: This study aimed to investigate the expression of programmed death-ligand 1 (PD-L1) and its associations with human papillomavirus (HPV) 16/18 DNA status, p16 expression, demographic, clinicopathologic and risk parameters in patients with oral squamous cell carcinoma (OSCC). Study design: A total of 85 formalin-fixed, paraffin-embedded OSCC specimens were collected. HPV16/18 DNA was detected by polymerase chain reaction. PD-L1 and p16 expressions were assessed using immunohistochemical technique. The immunostaining scores were calculated by combined positive score (CPS), previously described. The positive scoring value was determined at CPS ≥1, recommended by FDA. The associations between PD-L1 expression and HPV16/18 DNA status, p16 expression, demographic, clinicopathologic, and risk parameters were analyzed by Chi-square, Fisher's exact tests, and multivariate logistic regression. Results: PD-L1 expression was detected in 22 out of 85 cases of OSCC (25.9%). 16.5% of all cases were HPV 16/18-positive and 62.4% were p16-positive. Statistically, there were no significant associations between PD-L1 expression in OSCC and HPV16/18 DNA status, p16 expression, demographic and, clinicopathologic parameters or risk behaviors. Conclusion: Approximately one-fourth of OSCC cases were PD-L1-positive, suggesting candidacy for anti-PD-L1 immunotherapy. Furthermore, HPV infection and p16 expression were not involved with PD-L1 expression. Further clinical trials warrant the benefits of immunotherapy in patients with PD-L1-positive OSCC.

A German AWMF's S2e/realist synthesis and meta-narrative snapshot of craniomaxillofacial manifestations in COVID-19 patients: Rapid living update on 1 January 2021.

PURPOSES: To execute a review answering the following question: "Among novel coronavirus disease (COVID19) patients, what are craniomaxillofacial (CMF) manifestations?" based on the RAMESES and the German Association of Scientific Medical Societies (AWMF)'s S2e guidelines. METHODS: We performed a realist synthesis and meta-narrative review extracting data in English, French, German and Thai from PubMed/Medline, Embase, Biomed Central, Cochrane Library, and Thai Journals Online, until 1 January 2021. The primary outcome variable was CMF manifestations grouped into 5 categories: (1) mouth and throat, (2) nose, paranasal sinus, and skull base (3) ocular/orbital and periorbital tissue, (4) ear, and (5) craniofacial skin. Appropriate statistics was computed. RESULTS: Thirty-seven original articles meeting the inclusion criteria were analysed; all were in English and indexed in PubMed/Medline. Hand searches of their references yielded a total of 101 articles for the review. Most data were in low level of evidence and focused on smell and taste disturbances and non-specific orofacial lesions. Iatrogenic complications may occur in this body region. Conservative measures remained effective and were usually enough for patient care. CONCLUSION: Because SARS-CoV-2 infection is new and becomes the stringent worldwide pandemic within a short time period, most of the data on CMF symptoms are of low level evidence. Apart from taste and smell dysfunctions, non-specific CMF lesions can be found and treated conservatively. Treatment complications are possible. Dentists and CMF surgeons are privileged to examine the orofacial region and work closely with colleagues in other specialities to combat this pandemic.

Morphometric study of incisive, greater and lesser palatine foramina: a novel point of maxillary nerve block in a Thai population / Estudio morfométrico del foramen palatino incisivo, mayor y menor: un punto novedoso de bloqueo del nervio maxilar en una población tailandesa

SUMMARY: To study the morphometric location of the incisive, greater, and lesser palatine foramina for maxillary nerve block. Two hundred Thai dry skulls were randomly organized from the Forensic Osteology Research Center. The distances of the parameters were measured via Vernier caliper.: Thedistances from the incisive foramen to the incisive margin of the premaxilla were 10.93?2.42 mm in males and 10.98?2.06 mm in females. From the left side, the incisive foramen to the greater palatine foramen (GPF) was39.07?2.23mm in males and 38.57?2.41 mm in females, and from the right side were 39.81?2.37 mm in males and 38.62?2.53mm in females. From the left side, the incisive foramen to the lesser palatine foramen (LPF) was 43.16?2.23 mm in males and 41.84?2.42mm in females and from the right side were 42.93?2.14 mm in males and 41.76?2.61 mm in females. The GPF found at medial to the maxillary third molar were 94-95 % in males and 84 % in females. These findings suggest that the medial position to the third molar teeth be used as a landmark for a palatine nerve block in Thais. These findings will help dentists to perform local anesthetic procedures, especially the nasopalatine and greater palatine nerve blocks, more effectively.

RESUMEN: El objetivo de este trabajo fue estudiar la localización morfométrica de los forámenes palatinos incisivos, mayores y menores para el bloqueo del nervio maxilar. Se organizaron al azar doscientos cráneos secos tailandeses del Centro de Investigación de Osteología Forense. Las distancias de los parámetros se midieron mediante un calibre Vernier. Las distancias desde el foramen incisivo hasta el margen incisivo de la premaxila fueron 10,93 ? 2,42 mm en hombres y 10,98 ? 2,06 mm en mujeres. Desde el lado izquierdo, el foramen incisivo al foramen palatino mayor (FPM) fue de 39,07 ? 2,23 mm en los hombres y 38,57 ? 2,41 mm en las mujeres, y del lado derecho fue de 39,81 ? 2,37 mm en los hombres y 38,62 ? 2,53 mm en las mujeres. Del lado izquierdo, el foramen incisivo al foramen palatino menor (LPF) fue de 43,16 ? 2,23 mm en hombres y 41,84 ? 2,42 mm en mujeres y del lado derecho 42,93 ? 2,14 mm en hombres y 41,76 ? 2,61 mm en mujeres. El FPM encontrado medial al tercer molar maxilar fue 94-95 % en hombres y 84 % en mujeres. Estos hallazgos sugieren que la posición medial de los terceros molares se utilice como punto de referencia para un bloqueo del nervio palatino en individuos tailandeses. Estos hallazgos ayudarán, de manera más eficaz, a los dentistas a realizar procedimientos anestésicos locales, especialmente los bloqueos nasopalatinos y del nervio palatino mayor.

High Prevalence of Human Papillomavirus Type 18 in Oral Potentially Malignant Disorders in Thailand.

OBJECTIVES: The main objectives of this study were to investigate the detection rate of high-risk human papillomavirus types 16 and 18 (high-risk HPV16/18) in oral potentially malignant disorders (OPMDs) including oral leukoplakia (OL) and oral lichen planus (OLP) in a Thai population and their associations with demographic, risk habits, and clinicopathologic features. METHODS: Paraffin-embedded formalin-fixed specimens from 101 OL and 59 OLP patients with patients' demographic, risk habits, and clinicopathologic data were collected. Conventional qualitative polymerase chain reaction was used to detect high-risk HPV16/18 DNA. Associations between high-risk HPV type 16/18 and demographic, clinicopathologic, risk factors (tobacco and alcohol uses) of OPMDs were analysed by Chi-square or Fisher's exact test. The results with p value less than 0.05 were considered statistically significant. RESULTS: HPV16/18 DNA was found in both OL and OLP groups with the detection rate of 19.8% and 18.6%, respectively. Approximately 90% of high-risk HPV were HPV18 subtype. Additionally, in OL group, high-risk HPV was found more frequently in patients with moderate/severe dysplasia than that in mild dysplasia. Interestingly, in OLP group, high-risk HPV was only detected in atrophic/ulcerative subtypes. None of risk factors was associated with high-risk HPV. CONCLUSIONS: Approximately 19% of OPMDs were HPV16/18-positive. HPV18 DNA was predominantly detected in both OL and OLP patients (90%). Additionally, the detection rate of high-risk HPV was higher in more severe dysplastic cases of OL and more clinically severe cases of OLP.

Human Papillomavirus 16 and 18 Infection in Oral Cancer in Thailand: A Multicenter Study.

OBJECTIVES: To identify the prevalence of high-risk human papillomavirus (HPV) genotypes 16 and 18 among patients with oral squamous cell carcinoma (OSCC) in Thailand and investigate the associations of p16 expression and HPV16/18 with the demographic, clinicopathologic, and risk parameters. MATERIALS AND METHODS: A total of 403 formalin-fixed paraffin-embedded OSCC specimens from four centers in four regions were obtained. p16 expression was evaluated by immunohistochemistry. The detection of HPV16/18 DNA was performed by polymerase chain reaction.  Results: Of all, 172 specimens (42.7%) were presented with amplifiable extracted DNA. Among these, 62.8% were positive for p16, 8.1% were positive for HPV16/18, and 5.8% were positive for both methods. Of all HPV-positive specimens, HPV18 was detected in 57.1%; HPV16 in 14.3%; and HPV16 and 18 (co-infection) in 28.6%. The prevalence of HPV16/18 varied between centers, with the highest rate in the northern center (20.0%). There was no significant correlation between p16 expression and HPV16/18. There were no significant associations of p16 expression and/or HPV16/18 with all variables. CONCLUSIONS: The prevalence of HPV16/18 infection in OSCC geographically varied in Thailand, with the highest rate in the northern region. Poor correlation between p16 and HPV16/18 suggests p16 not be used as a surrogate marker for HPV-positive OSCC.
.

Ten-Year Outcome of Different Treatment Modalities for Squamous Cell Carcinoma of Oral Cavity

Objective: This study reports outcomes of squamous cell carcinoma of oral cavity (SCCOC) patients with different treatment modalities. Materials and Methods: We evaluated the treatment outcomes of 775 newly diagnosed SCCOC patients treated in our hospital between 2001 and 2010. Outcome data were obtained from the medical records. Survival rates were estimated by the Kaplan-Meyer method. Cox-proportional-hazard regression models were used to compare the risk of death among all risk factors. Results: The patients were divided into group 1) surgery ± adjuvant radiotherapy (RT) (n = 323) or group 2) RT ± chemotherapy (CT) for curative intent (n = 315) or group 3) RT/CT for palliative intent (n = 137). The overall 10-year survival rate was 17%. Statistically significant difference was noted in 10-year overall survival when SCCOC was managed surgically as compared to curative RT and palliative RT/CT with 25.3 %, 12.9%, 4.7%, respectively. The hazard ratio of cancer death in group 1 was 2.0 (95% CI 1.7-2.4) as compared to group 2. Conclusion: This study suggested that surgery must be the mainstay of treatment in locally advanced stage SCCOC. Palliative RT/CT still offered long term survival in some SCCOC patients.

Akt2 and p-Akt overexpression in oral cancer cells is due to a reduced rate of protein degradation.

OBJECTIVE: To quantitatively measure the increased expression of Akt2 and its phosphorylated form (p-Akt) in oral cancer cell lines and investigate the post-translational mechanism for Akt2 and p-Akt overexpression. METHODS: Three oral cancer cell lines and three cell lines of primary human oral keratinocytes (HOKs) were cultured and the degrees of Akt2 and p-Akt expression was evaluated by immunoblot analysis and flow cytometry. Each cell line was incubated with cycloheximide, an inhibitor of new protein synthesis, for various times to quantitatively determine the remaining expression levels of Akt2 and p-Akt by flow cytometry. The localization of Akt2 and p-Akt was assessed by immunofluorescence. RESULTS: The levels of Akt2 and p-Akt proteins were significantly higher in cancer cell lines than those in HOKs (P < 0.05). When the new protein synthesis was blocked by cycloheximide treatment, the degradation rate of Akt2 and p-Akt in oral cancer cells was significantly lower than that in HOKs (P < 0.05). Both Akt2 and p-Akt were more intensely stained in the cytoplasm of cancer cells, whereas HOKs expressed Akt2 and p-Akt only minimally. CONCLUSION: Both Akt2 and p-Akt were overexpressed in oral cancer cells, which may be partly explained by a reduced rate of protein degradation in order to maintain high cytosolic levels.

p16 - a Possible Surrogate Marker for High-Risk Human Papillomaviruses in Oral Cancer?

BACKGROUND: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. OBJECTIVE: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. MATERIALS AND METHODS: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. RESULTS: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (<0.05, OR 20, 95% CI 1.9-211.8; <0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. CONCLUSIONS: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

Ten-year analysis of oral cancer focusing on young people in northern Thailand.

The objective of the present study was to assess the current situation of oral squamous cell carcinoma (OSCC) in northern Thailand, with an emphasis on patients <40 years of age. Medical records of patients histologically diagnosed with OSCC were collected from the Cancer Registry of Maharaj Nakorn Chiang Mai Hospital, Thailand between 2001 and 2010. The clinico-demographic data of patients aged <40 years (young group) and those aged ≥40 years (old group) were compared. A total of 874 patients were included in this study, of which 4.1% were <40 years of age. The tongue was the most common cancer site in both age groups. Most patients in both age groups were diagnosed with oral cancer at stage IV. Tobacco smoking (62.3%) and alcohol consumption (52.3%) were the most common risk factors in both age groups. However, the rates of betel quid chewing (17.5%) had decreased from those found in our study in the previous decade (50.2%); these rates were not found in the young group. The 5-year survival rate was 27.4% for the old group and 56.2% for the young group. OSCC remains a serious oral health problem in northern Thailand, and it has not been resolved among young adults.

Roles of Human Papillomaviruses and p16 in Oral Cancer.

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

Saliva-Based Screening of High-Risk Human Papillomavirus Strains: Detection in Female Indonesian and Thai Dental Students.

BACKGROUND: Currently it is believed that human papillomaviruses (HPV) are associated with the development of some oral/oropharyngeal cancers. It has been suggested that these viruses influence carcinogenesis in both smokers and non-smokers. Data on the prevalence of HPV in healthy adults are thus needed to estimate the risk of oral/oropharyngeal cancer. The aim of this study was to assess the prevalence of oral HPV in healthy female adults in Indonesia and Thailand. MATERIALS AND METHODS: Healthy female students from the Faculties of Dentistry of Universitas Indonesia and Chiang Mai University were asked to participate in this pilot study. DNA was extracted from saliva specimens and screened for HPV16 and HPV18 using PCR. RESULTS: The age, marital status and sexual experience of the subjects between the two countries were not significantly different. Eight (4%) and 4 (2%) samples were positive for HPV16 and HPV18, respectively. Fisher's Exact test found a significant difference between HPV16 positivity in subjects who were married and had sexual intercourse but not for HPV18. CONCLUSIONS: This study successfully detected presence of HPV16 and HPV18 DNA in a number of saliva samples from female dental school students. Marital status, experience of sexual intercourse and safe sexual practice are related to the possibility of finding HPV DNA finding in saliva. Dentists, physicians and other health care professionals may gain significant value from the findings of this study, which provide an understanding of the nature of HPV infection and its risk to patient health and disease.

Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation.

We report on a 4-year-old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood-onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.

Enamel-renal-gingival syndrome and FAM20A mutations.

The enamel-renal syndrome of amelogenesis imperfecta (AI) and nephrocalcinosis, and the amelogenesis imperfecta-gingival fibromatosis syndrome have both been associated with mutations in FAM20A. We report on two unrelated Thai patients with three novel and one previously reported mutations in FAM20A with findings suggesting both disorders, including hypoplastic AI, gingival fibromatosis, unerupted teeth, aggressive periodontitis, and nephrocalcinosis/nephrolithiasis. Additional findings consisted of a supernumerary premolar, localized aggressive periodontitis, thin alveolar bone, vitamin D deficiency-associated hyperparathyroidism, and heterotopic calcification in other tissues, including lungs, dental pulp, gingiva, dental follicles, and periodontal tissues, and early cessation of limited menstruation. Greater promotory activity of urine on calcium oxalate crystal growth compared to controls may help to explain the pathogenesis, and suggest that FAM20A mutations can contribute to nephrocalcinosis/nephrolithiasis. Our findings expand the phenotypic spectrum of FAM20A mutations. Since both of our patients and a large number of previously reported cases had all the important features of both syndromes, including AI, renal anomalies, and gingival fibromatosis, we are convinced that these two disorders actually are the same entity. The name of enamel-renal-gingival syndrome is suggested.

Pemphigus, discoid lupus erythematosus, and dermatomyositis during an 8-year follow-up period: a case report.

A 36-year-old Thai woman presented with a painful, burning sensation in the gingiva and desquamative gingivitis. Findings from histopathologic and direct immunofluorescence examination of the maxillary gingiva confirmed a diagnosis of pemphigus. Two months later, she developed a round erythematous lesion on her face, and findings from a skin biopsy were consistent with lupus erythematosus. Four years after initial presentation, the patient developed amyotrophic dermatomyositis. Seven years after initial presentation, she developed joint pain and tenositis of the neck, shoulders, knees and ankles, which was diagnosed as asymmetric polyarthritis and multiple enthesopathy. There are no previous reports of pemphigus, discoid lupus erythematosus, and dermatomyositis in a Thai patient.Fluocinolone acetonide 0.1% in Orabase and systemic steroid were effective in treating oral PV in this patient. The gingiva showed complete remission after 10 months of treatment and remission with recession at 8.5 years of follow-up.

Epithelial-mesenchymal transition in oral squamous cell carcinoma.

Oral cancer is one of the drastic human cancers due to its aggressiveness and high mortality rate. Of all oral cancers, squamous cell carcinoma is the most common accounting for more than 90%. Epithelial-mesenchymal transition (EMT) is suggested to play an important role during cancer invasion and metastasis. Recently, emerging knowledge on EMT in carcinogenesis is explosive, tempting us to analyze previous studies on EMT in oral squamous cell carcinoma (OSCC). In this paper, we have first addressed the general molecular mechanisms of EMT, evidenced by alterations of cell morphology during EMT, the presence of cadherin switching, turning on and turning off of many specific genes, the activation of various signaling pathways, and so on. The remaining part of this paper will focus on recent findings of the investigations of EMT on OSCC. These include the evidence of EMT taking place in OSCC and the signaling pathways employed by OSCC cells during their invasion and metastasis. Collectively, with the large body of new knowledge on EMT in OSCC elaborated here, we are hopeful that targeting treatment for OSCC will be developed.

Overexpression and activation of Akt2 protein in oral squamous cell carcinoma.

Aberrations of signal transducers in PI3K/Akt pathway have been found in many human cancers, and may play a critical role in carcinogenesis. Advanced research on oral cancer treatments, using novel agents targeting the PI3K/Akt signaling pathway, is being investigated with promising results. The objectives of this study were (1) to investigate expression of pan-Akt and its phosphorylated form (p-Akt), Akt1, and Akt2 in oral squamous cell carcinoma (OSCC) specimens (n=20) by immunohistochemistry, and (2) to determine mRNA expression of three Akt isoforms, including Akt1, Akt2, and Akt3, as well as their respective proteins, in five oral cancer cell lines and normal human oral keratinocytes (HOKs) by RT-PCR and Western blot assays. The results show that pan-Akt was expressed in 80% of OSCC cases, while Akt1, Akt2, and p-Akt were expressed in all OSCC cases. An intense expression of p-Akt at the invasive fronts of some OSCC samples was observed. Consistent with the immunohistochemical findings, p-Akt and Akt2 were overexpressed in all oral cancer cell lines in comparison with HOKs, whereas Akt2 mRNA was constitutively expressed, suggesting post-transcriptional regulation. In contrast, Akt1 mRNA and protein were constitutively expressed in all oral cancer cell lines and HOKs, while Akt3 mRNA appeared to be minimally expressed. In summary, these findings demonstrate that Akt2 and p-Akt are overexpressed in OSCC and may be involved in carcinogenesis, and suggest that post-transcriptional modification of Akt2 in OSCC may occur.

Aberrant expression of Smad4, a TGF-beta signaling molecule, in oral squamous cell carcinoma.

Although carcinogenesis of oral squamous cell carcinoma (OSCC) has been studied by many investigators in the past decade, the available evidence about its molecular mechanism is inconclusive. The objective of the present study was to compare expression of Smad4, a signaling molecule of the transforming growth factor beta (TGF-beta) pathway, between OSCC and normal oral mucosa. We assayed expression of Smad4 in OSCC and normal oral mucosa by performing immunohistochemistry using paraffin-embedded tissue samples. We also compared expression of Smad4 protein between OSCC lines and normal oral keratinocytes, using Western blot analysis. Smad4 expression was observed in only 60% of OSCC tissue samples, whereas it was observed in 82% of normal oral mucosa samples. Reduced Smad4 expression was clearly observed in all OSCC lines, compared with normal oral keratinocytes. These findings suggest that aberration of the TGF-beta pathway, as indicated by a reduction or absence of Smad4 expression, promotes carcinogenesis of OSCC.

Co-expression of p53 and Ki67 and lack of EBV expression in oral squamous cell carcinoma.

BACKGROUND: The objectives of the study were to determine the association between Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC), to compare the expression of p53 and Ki67 between normal oral mucosa, oral hyperkeratosis, oral pre-malignant dysplasia, and OSCC, and to determine the correlation between the expression of p53 and Ki67 in OSCC. METHODS: The expression of EBV mRNA was studied by in situ hybridization technique in 24 cases of OSCC, and the expression of p53 and Ki67 was investigated by immunohistochemical method in 19 cases of OSCC, 7 cases of oral pre-malignant dysplasia, 6 cases of oral hyperkeratosis, and 5 cases of normal oral epithelium. RESULTS: None of OSCC cases expressed EBV-encoded RNA (EBER) transcripts. The labeling indices (LI) of p53- and Ki67-positive cells were significantly higher in OSCC than in oral pre-malignant dysplasia, oral hyperkeratosis, and normal oral mucosa (P < 0.05). A significant correlation between the LI of p53- and Ki67-positive cells was observed in OSCC (r = 0.6; P = 0.01). CONCLUSIONS: These findings suggested that the co-expression of p53 and Ki67 may play roles in carcinogenesis of OSCC and p53 overexpression may promote cell proliferation in OSCC. Furthermore, EBV does not appear to be a risk factor for OSCC particularly in the population of northern Thailand.

Oral white sponge naevus: case report.

The clinical appearances of white sponge naevus may mimic other oral white lesions, including premalignant leukoplakia but, unlike leukoplakia, white sponge naevus does not have malignant potential. This article presents a case of an irregular white lesion on the oral mucosa with findings suggestive of white sponge naevus.