Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up.

BACKGROUND: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma (OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study, we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specific Spanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosis measures. MATERIAL AND METHODS: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospital centre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival were calculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression). RESULTS: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) and alcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailed the 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were 39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC cases referred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with an oral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatment. CONCLUSIONS: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prognosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights the better survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and the dental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the early diagnosis and multidisciplinary management of this malignant neoplasm.

Diagnostic yield of sentinel lymph node biopsy in oral squamous cell carcinoma T1/T2-N0: systematic review and meta-analysis.

The objective of this study was to conduct a systematic review and meta-analysis on the efficacy of sentinel lymph node biopsy (SLNB) in T1/T2-N0 oral squamous cell carcinoma (OSCC). A systematic review of the literature on SLNB until March 2019 was conducted. The review was organized according to the PRISMA protocol, considering the following PICO (population, intervention, comparison, outcome) question: What is the sensitivity of sentinel lymph node biopsy in OSCC? 'P' was patients with head and neck squamous cell carcinoma T1/2-N0; 'I' was SLNB; 'C' was neck treated with elective neck dissection and haematoxylin-eosin histopathology; 'O' was sensitivity and specificity. A meta-analysis and meta-regression were performed on the selected studies. The sensitivity of SLNB was up to 88% (95% confidence interval (CI) 72-96%) and specificity was up to 99% (95% CI 96-100%). The area under the summary receiver operating characteristic curve was 0.99 (95% CI 0.98-1.00). In the four studies where immunohistochemistry was performed, both the sensitivity and specificity were higher than in the studies without immunohistochemistry: 93% (95% CI 88-97%) and 98% (95% CI 96-100%), respectively. In conclusion, SLNB is an effective technique for treating patients with some types of stage T1/2-N0 OSCC. Some parameters such as immunohistochemistry could determine the level of diagnostic accuracy.

Clinicopathological and prognostic characterization of oral lichenoid disease and its main subtypes: A series of 384 cases.

BACKGROUND: To clinicopathologically characterize the diagnosis of oral lichenoid disease (OLD) and its main subtypes: oral lichen planus (OLP) and oral lichenoid lesion (OLL), in order to correctly asses their prognosis. MATERIAL AND METHODS: Ambispective cohort study of 384 patients with diagnosis of OLD, based on pre-established clinical and histopathological criteria. We have analysed 272 (70.8%) women and 112 (29.2%), whose mean age was 57.1+/-11.8 years (range 21-90); minimum follow-up time was 36 months. A specific protocol was designed for this study, where we gathered the data of each patient, including malignant transformation. RESULTS: OLP was diagnosed in 229 cases (77.9%) and OLL in 85 (22.1%). Tobacco consumption was found in 20.3% of the patients and alcohol intake in 41.1%. Liver pathology was present in 10.7% of the cases, thyroid pathology in 11.5%, arterial hypertension in 15.6%, diabetes mellitus in 7.6%, psycho-emotional disorders in 33.3%, skin involvement in 12% and genital involvement in 4.9%. Ten patients (2.6%) developed an oral squamous cell carcinoma, 5 (1.7%) with OLP and 5 (5.9%) with OLL. CONCLUSIONS: OLD is a potentially malignant disorder of the oral mucosa which has to be correctly diagnosed as either OLP or OLL, since the risk of malignancy of these subtypes is significantly different.

Validation of microRNA expression profile in Oral Lichenoid Disease through cytological samples.

BACKGROUND: To validate oral exfoliative cytology in the analysis of the microRNA expression profile in Oral Lichenoid Disease (OLD). MATERIAL AND METHODS: The expression of 13 microRNAs identified and presented by our group in a previous study was analyzed in 26 cases, 16 diagnosed as OLD and 10 controls with no oral mucosal pathology. Cytological samples from the oral mucosa obtained using an Orcellex toothbrush were analyzed using RT-qPCR and TaqMan microRNA assays. RESULTS: The aberrant expression was validated for 2 microRNAs (miR-146a-5p and miR-7-1-3p) of those previously recognized in the biopsy study. CONCLUSIONS: This is the first time that oral exfoliative cytology is validated in a study of the alterations of the expression of microRNAs in OLD. The alteration of miR-146a and miR-7 compared to controls was validated. These microRNAs are associated with both inflammatory and carcinogenic phenomena that are involved in the etiopathogenesis of this potentially malignant oral disorder.

Evaluation of the osteoclastogenic process associated with RANK / RANK-L / OPG in odontogenic myxomas.

BACKGROUND: Odontogenic myxoma (OM) is a benign intraosseous neoplasm that exhibits local aggressiveness and high recurrence rates. Osteoclastogenesis is an important phenomenon in the tumor growth of maxillary neoplasms. RANK (Receptor Activator of Nuclear Factor κappa B) is the signaling receptor of RANK-L (Receptor activator of nuclear factor kappa-Β ligand) that activates the osteoclasts. OPG (osteoprotegerin) is a decoy receptor for RANK-L that inhibits pro-osteoclastogenesis. The RANK / RANKL / OPG system participates in the regulation of osteolytic activity under normal conditions, and its alteration has been associated with greater bone destruction, and also with tumor growth. OBJECTIVES: To analyze the immunohistochemical expression of OPG, RANK and RANK-L proteins in odontogenic myxomas (OMs) and their relationship with the tumor size. MATERIAL AND METHODS: Eighteen OMs, 4 small (<3 cm) and 14 large (> 3cm) and 18 dental follicles (DF) that were included as control were studied by means of standard immunohistochemical procedure with RANK, RANKL and OPG antibodies. For the evaluation, 5 fields (40x) of representative areas of OM and DF were selected where the expression of each antibody was determined. Descriptive and comparative statistical analyses were performed with the obtained data. RESULTS: There are significant differences in the expression of RANK in OM samples as compared to DF (p = 0.022) and among the OMSs and OMLs (p = 0.032). Also a strong association is recognized in the expression of RANK-L and OPG in OM samples. CONCLUSIONS: Activation of the RANK / RANK-L / OPG triad seems to be involved in the mechanisms of bone balance and destruction, as well as associated with tumor growth in odontogenic myxomas.

MicroRNAs expression profile in solid and unicystic ameloblastomas.

OBJECTIVES: Odontogenic tumors (OT) represent a specific pathological category that includes some lesions with unpredictable biological behavior. Although most of these lesions are benign, some, such as the ameloblastoma, exhibit local aggressiveness and high recurrence rates. The most common types of ameloblastoma are the solid/multicystic (SA) and the unicystic ameloblastoma (UA); the latter considered a much less aggressive entity as compared to the SA. The microRNA system regulates the expression of many human genes while its deregulation has been associated with neoplastic development. The aim of the current study was to determine the expression profiles of microRNAs present in the two most common types of ameloblastomas. MATERIAL & METHODS: MicroRNA expression profiles were assessed using TaqMan® Low Density Arrays (TLDAs) in 24 samples (8 SA, 8 UA and 8 control samples). The findings were validated using quantitative RTqPCR in an independent cohort of 19 SA, 8 UA and 19 dentigerous cysts as controls. RESULTS: We identified 40 microRNAs differentially regulated in ameloblastomas, which are related to neoplastic development and differentiation, and with the osteogenic process. Further validation of the top ranked microRNAs revealed significant differences in the expression of 6 of them in relation to UA, 7 in relation to SA and 1 (miR-489) that was related to both types. CONCLUSION: We identified a new microRNA signature for the ameloblastoma and for its main types, which may be useful to better understand the etiopathogenesis of this neoplasm. In addition, we identified a microRNA (miR-489) that is suggestive of differentiating among solid from unicystic ameloblastoma.

The role of microRNAs in oral lichenoid disorders. Systematic review.

BACKGROUND: Certain changes in the microRNA expression are considered to be associated with chronic inflammatory processes and with the malignant transformation of oral potentially malignant disorders. The purpose of this systematic review is to update the existing data on the aberrant microRNA expression profiles identified in oral lichenoid disease (OLD). MATERIAL AND METHODS: A search in PubMed-Medline and Scopus was performed on the English literature published between 2010 and August 2016 using the following keywords: oral lichenoid disease, oral lichen planus and microRNA. RESULTS: Originally, 25 articles were considered, of which 12 case-control articles were selected according to the inclusion/exclusion criteria. CONCLUSIONS: OLD seems to have altered microRNA expression profile. Certain altered microRNAs (146a, 155) may be useful as biomarkers for this disorder. More studies including larger number of cases are needed in order to study further on the biological processes and on the regulation pathways of these altered microRNAs.

Histopathological characterization of the oral lichenoid disease subtypes and the relation with the clinical data.

BACKGROUND: The aim of the study was to analyze the histopathological characteristics of samples with a diagnosis of oral lichenoid disease (OLD) and their link with the location and the type of clinical lesion, and the clinicopathological subtypes. MATERIAL AND METHODS: Retrospective study on 85 consecutive patients diagnosed with OLD (58 women and 27 men, mean age of 57.7 years). Clinical and histopathological characterization of each case (modified WHO criteria). Collection of the clinical and histopathological data of the lesions. Descriptive and comparative statistical analysis of the results. RESULTS: The 78.8% of the cases were considered clinically typical while the 21.2% were considered compatible. Histologically, 52.9% were classified as typical and 47.1% as compatible. Biopsies from "plaque-like" lesions presented hyperkeratosis (p>0.001) and epithelial dysplasia (p=0.06) more frequently. Furthermore, acute inflammation was more evident in erosive-ulcerative lesions (p=0.001). Differences regarding the location of the biopsy were statistically non-significant. However, 42.9% of the tongue biopsies showed epithelial dysplasia. CONCLUSIONS: The histopathological aspect of this disorder is not specific and does not allow us to differentiate between the main subtypes. Therefore, the main reasons to perform a biopsy in this disorder are to define the differential diagnosis and to rule out epithelial dysplasia or a carcinoma. The final histopathological result may be subject to the type of lesion that is biopsied.

Genomewide miRNA profiling of oral lichenoid disorders and oral squamous cell carcinoma.

OBJECTIVE: To dissect the aberrant microRNA profile of oral lichenoid disorders (OLD) by analyzing the larger set of OLD samples tested so far. MATERIALS AND METHODS: MicroRNA expression profiles were assessed using TLDA card in 32 samples (16 OLD, 8 OSCC, and 8 control). The findings were validated using RT-qPCR in an independent cohort of 91 samples. RESULTS: We identified 20 differentially expressed microRNAs in OLD, of which several are functionally related to cell proliferation, response to organic substances, or immune processes. Further validation of the top-ranked microRNAs revealed that they were all aberrantly expressed in OLD. CONCLUSION: We have identified a new microRNA signature associated with OLD that may provide a meaningful basis for better understanding the physiopathology of the disease. In addition, we validated seven microRNAs whose expression was shown to be higher in OLD tissue in comparison with the control and OSCC tissues.

Global DNA methylation: uncommon event in oral lichenoid disease.

OBJECTIVES: Accumulating evidence indicates that aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. The aim of this study was to perform the first wide DNA methylation study in OLD in order to investigate the relevance of DNA methylation changes in this premalignant disorder. MATERIALS AND METHODS: Two different Illumina microarray platforms, namely the GoldenGate Cancer Panel I and the HumanMethylation27 DNA Analysis BeadChip, were utilized in the discovery phase to interrogate the methylation profile of 59 OLD cases and 9 healthy individuals. Top-ranked genes were further validated by pyrosequencing in a second sample set consisting of 160 OLD and 65 controls. RESULTS: Our results show that the frequency of aberrant DNA methylation is rare in OLD, and this finding was further corroborated by pyrosequencing in the biological validation. CONCLUSIONS: These findings reinforce the notion that molecular alterations associated with oral carcinogenesis do not seem to be common events in OLD, which in turn might explain the low rate of malignization of this disorder.