AIMS: To determine the usefulness of immunohistochemical techniques and FISH of the tumour suppressor TP 53 gene to identify microinvasion in marginal tissue sections and to relate the possible correlation between protein expression and genetic aberrations in OSCC cases in Malaysia.
METHODS: Immunohistochemistry and FISH of TP 53 genes were applied on 26 OSCC formalin fixed paraffin embed (FFEP) blocks selected from two oral cancer referral centers in Malaysia.
RESULTS: For p53 protein immunohistochemistry, 96% of the 26 OSCC studied showed positive immunostaining at the excision margins. In FISH assay, 48.9±9.7% of the cancerous cells were monoploid for p53 probe signals, 41.0±9.5 % were diploid, and 10.2±7.8 % were polyploid. A correlation between p53 immunostaining and TP53 gene aberrations was noted (p< 0.05).
CONCLUSIONS: Immunohistochemical analysis of p53 protein expression and FISH of TP53 gene could be applied as screening tool for microinvasion of OSCC.
METHOD: English language literature in major databases from the last 20 years was searched using controlled vocabulary and keywords. Strict inclusion and exclusion criteria were followed for selection of studies. The quality assessment was done as per the QUADAS tool 2 by three independent reviewers. The metanalysis was performed by using random effect model. Standardized mean difference (SMD) was considered as the effect measure. Statistical software used was STATA version 13.1.
RESULTS: With all inclusion and exclusion criteria, eight studies could qualify for metanalysis. The pooled estimate is found to be 0.13 (-0.35, 0.62), P = .585, which is statistically not significant. This indicates that there is a no significant difference in the fold change between metastasis and no metastasis groups. P-value of chi-square statistic for heterogeneity is
PURPOSE: Here, we investigated whether OSCC cells were sensitive towards zerumbone treatment and further determined the molecular pathways involved in the mechanism of action.
METHODS: Cytotoxicity, anti-proliferative, anti-migratory and anti-invasive effects of zerumbone were tested on a panel of OSCC cell lines. The mechanism of action of zerumbone was investigated by analysing the effects on the CXCR4-RhoA and PI3K-mTOR pathways by western blotting.
RESULTS: Our panel of OSCC cells was broadly sensitive towards zerumbone with IC50 values of less than 5 µM whereas normal keratinocyte cells were less responsive with IC50 values of more than 25 µM. Representative OSCC cells revealed that zerumbone inhibited OSCC proliferation and induced cell cycle arrest and apoptosis. In addition, zerumbone treatment inhibited migration and invasion of OSCC cells, with concurrent suppression of endogenous CXCR4 protein expression in a time and dose-dependent manner. RhoA-pull down assay showed reduction in the expression of RhoA-GTP, suggesting the inactivation of RhoA by zerumbone. In association with this, zerumbone also inhibited the PI3K-mTOR pathway through the inactivation of Akt and S6 proteins.
CONCLUSION: We provide evidence that zerumbone could inhibit the activation of CXCR4-RhoA and PI3K-mTOR signaling pathways leading to the reduced cell viability of OSCC cells. Our results suggest that zerumbone is a promising phytoagent for development of new therapeutics for OSCC treatment.
OBJECTIVES: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.
METHODS: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.
RESULTS: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.
CONCLUSIONS: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.
METHODS: A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014).
RESULTS: A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027).
CONCLUSION: Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure.
MATERIALS AND METHODS: A total of 81 cases of oral cancers were matched with 162 controls in this hospital-based study. Information on sociodemographic characteristics and details of risk habits (duration, frequency and type of tobacco consumption and betel quid chewing) were collected. Association between smoking and betel quid chewing with oral cancer were analysed using conditional logistic regression.
RESULTS: Slightly more than half of the cases (55.6%) were smokers where 88.9% of them smoked kretek. After adjusting for confounders, smokers have two fold increased risk, while the risk for kretek consumers and those smoking for more than 10 years was increased to almost three-fold. Prevalence of betel quid chewing among cases and controls was low (7.4% and 1.9% respectively). Chewing of at least one quid per day, and quid combination of betel leaf, areca nut, lime and tobacco conferred a 5-6 fold increased risk.
CONCLUSIONS: Smoking is positively associated with oral cancer risk. A similar direct association was also seen among betel quid chewers.
METHODS: Clinico-pathological data from a previously treated cohort of 590 newly presenting PMD patients were reviewed and clinical outcomes categorized as disease free, persistent PMD or MT. Multiple logistic regression was used to predict the probability of MT in the cohort using age, gender, lesion type, site and incision biopsy histopathological diagnoses. Internal validation and calibration of the model was performed using the bootstrap method (n = 1000), and bias-corrected indices of model performance were computed.
RESULTS: Potentially malignant disorders were predominantly leukoplakias (79%), presenting most frequently at floor of mouth and lateral tongue sites (51%); 99 patients (17%) developed oral squamous cell carcinoma during the study period. The nomogram performed well when MT predictions were compared with patient outcome data, demonstrating good bias-corrected discrimination and calibration (Dxy = 0.58; C = 0.790), with a sensitivity of 87% and specificity 63%, and a positive predictive value of 32% and negative predictive value 96%.
CONCLUSION: The "Newcastle Nomogram" has been developed to predict the probability of MT in PMD, based on an internally validated statistical model. Based upon readily available and patient-specific clinico-pathological data, it provides clinicians with a pragmatic diagrammatic aid for clinical decision-making during diagnosis and management of PMD.