Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma.

BACKGROUND: Increased lipogenesis and lipid droplet accumulation are observed in diverse tumors, and these processes are associated with poor prognosis in several tumors, representing potential therapeutic targets. The presence of lipid droplets in odontogenic tissues and/or tumors is unknown. METHODS: Immunohistochemistry for perilipin 1 and adipophilin was performed in 12 human tooth germs (TG), 27 conventional ameloblastoma (AM), and 8 ameloblastic carcinoma (AC) samples. Cytoplasmic staining was analyzed using an immunoreactive score (IRS), and the results were compared for the TG, AM, and AC samples by Kruskal-Wallis test followed by Dunn's post-test and confirmed by Mann-Whitney U test. RESULTS: Perilipin 1 was negative in 91.7% of the TG samples, positive in 48.2% of the AM samples, and positive in 87.5% of the AC samples. Adipophilin was positive in 100% of the TG samples, 92.6% of the AM samples, and 100% of the AC samples. The perilipin 1 and adipophilin IRS revealed statistically significant differences between the TG, AM, and AC samples (p = .007 and p = .018, respectively). The perilipin 1 levels among the TG and AC samples were statically significant (**p = .0085), as well as the adipophilin levels when TG and AM samples were compared (**p < .0029). CONCLUSIONS: Adipophilin exhibits significant activity in human tooth development. The immunoexpression of perilipin 1 and adipophilin in the AM and AC samples suggests the presence of lipid droplets, providing further evidence of metabolic alterations in these tumors. Additional studies with larger samples and alternative techniques are necessary to confirm these findings.

Expression of caveolin-1 in tooth germ, ameloblastoma and ameloblastic carcinoma / Expresión de caveolina-1 en germen dental ameloblastoma y carcinoma ameloblástico

Background: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in sev-eral biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been as-sociated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear.Material and Methods: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium(n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) byimmunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot.Results: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemicalpositivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were signifi-cantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue,as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1immunoexpression patterns throughout the stages of TG show its importance during odontogenesis.Conclusions: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingivalepithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immu-noexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformationprocess. However, future studies are needed to clarify and confirm these hypotheses.(AU)

Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review.

BACKGROUND: Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments. AIM: To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors. METHODS: An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed. RESULTS: Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of k = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E. CONCLUSION: The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review.

This manuscript provides an update to the literature on molecules with roles in tumor resistance therapy in head and neck squamous cell carcinoma (HNSCC). Although significant improvements have been made in the treatment for head and neck squamous cell carcinoma, physicians face yet another challenge-that of preserving oral functions, which involves the use of multidisciplinary therapies, such as multiple chemotherapies (CT) and radiotherapy (RT). Designing personalized therapeutic options requires the study of genes involved in drug resistance. This review provides an overview of the molecules that have been linked to resistance to chemotherapy in HNSCC, including the family of ATP-binding cassette transporters (ABCs), nucleotide excision repair/base excision repair (NER/BER) enzymatic complexes (which act on nonspecific DNA lesions generated by gamma and ultraviolet radiation by cross-linking and forming intra/interchain chemical adducts), cisplatin (a chemotherapeutic agent that causes DNA damage and induces apoptosis, which is a paradox because its effectiveness is based on the integrity of the genes involved in apoptotic signaling pathways), and cetuximab, including a discussion of the genes involved in the cell cycle and the proliferation of possible markers that confer resistance to cetuximab.

Severity of Oral Mucositis in Children following Chemotherapy and Radiotherapy and Its Implications at a Single Oncology Centre in Durango State, Mexico.

BACKGROUND: Mucositis is an adverse effect of chemotherapy (QT) and/or radiotherapy (RT). The purpose of this study was to investigate the occurrence of oral mucositis in children undergoing cancer treatment. METHODS: Fifty-one children with cancer who had received QT, RT, or both (QT-RT) underwent clinical evaluations; World Health Organization criteria were used to establish the degree and severity of mucositis. The correlations between the clinical data, type of cancer, and therapy were statistically analysed. RESULTS: Mucositis was present in 88.23% of the patients; 57.78%, 7.78%, and 24.44% received QT, RT, and QT-RT, respectively. Severity scores of 1 and 2 were the most common; scores of 3-4 were observed in patients who received QT-RT or more than 7 treatment cycles. There was a significant association between mucositis, the type of treatment, and the number of cycles received (p < 0.05). CONCLUSION: It is important to implement therapeutic protocols that help maintain excellent oral health and reduce the risk of oral mucositis. Stomatologists should be consulted to assess patients' oral cavities and provide preventive treatment prior to QT and/or RT administration. It is important to integrate a stomatologist into the oncological working group to focus on preventing and managing oral mucositis.

Differences in E-Cadherin and Syndecan-1 Expression in Different Types of Ameloblastomas.

Ameloblastomas are a group of benign, locally aggressive, recurrent tumors characterized by their slow and infiltrative growth. E-Cadherin and syndecan-1 are cell adhesion molecules related to the behavior of various tumors, including ameloblastomas. Ninety-nine ameloblastoma samples were studied; the expression of E-cadherin and syndecan-1 were evaluated by immunohistochemistry. E-Cadherin and epithelial syndecan-1 were more highly expressed in intraluminal/luminal unicystic ameloblastoma than in mural unicystic ameloblastoma and solid/multicystic ameloblastoma, whereas the stromal expression of syndecan-1 was higher in mural unicystic ameloblastoma and solid/multicystic ameloblastoma. Synchronicity was observed between E-cadherin and epithelial syndecan-1; the expression was correlated with intensity in all cases. There was a strong association between expression and tumor size and recurrence. The evaluation of the expression of E-cadherin and syndecan-1 are important for determining the potential aggressiveness of ameloblastoma variants. Future studies are required to understand how the expression of these markers is related to tumor aggressiveness.

Comparison between Manual and Automated Methods for Ki-67 Immunoexpression Quantification in Ameloblastomas.

Ameloblastoma is a common and unpredictable odontogenic tumor with high relapse rates. Several studies assessing the proliferative capacity of these neoplasms have been published, mainly using the protein Ki-67. Cell counts must be completed to determine the cell proliferation rate. Multiple methods have been developed for this purpose. The most widely used method is the labeling index, which has undergone changes over time to better facilitate cell counting. Here, we compared manual cell counting methods with automated cell counting (ImmunoRatio) to determine the relative effectiveness of these methods. The results suggest that ImmunoRatio, a free software tool, may be highly advantageous and provide results similar to manual cell counting methods when used with the appropriate calibration. However, ImmunoRatio has flaws that may affect the labeling index results. Therefore, this automated cell counting method must be supplemented with manual cell counting methods.

Carcinomas de cabeza y cuello, experiencia de un centro oncológico del estado de Durango, México / Head and neck carcinomas, experience of a cancer center in the state of Durango, Mexico

Antecedentes: los carcinomas de cabeza y cuello son relativamente frecuentes, presentan diversos tipos histológicos y características clínicas, mismas que se asocian con una variedad de riesgos de mortalidad. Objetivo: El propósito de este trabajo fue examinar en un periodo de cinco años carcinomas de cabeza y cuello tratados en el Centro Estatal de Cancerología. Material y métodos: Este estudio se realizó de manera retrospectiva, se revisaron factores de riesgo y tratamientos, se hicieron análisis univariados y multivariados para evaluar factores pronóstico y supervivencia. Resultados: Se obtuvieron un total de 32 expedientes que cumplían con las características del estudio, el periodo de seguimiento fue de 2 a 32 meses. La variante histológica predominante fue carcinoma epidermoide, el tratamiento primario más común fue cirugía. Conclusiones: La supervivencia en los carcinomas de cabeza y cuello disminuye en pacientes en etapas clínicas avanzadas, edad e historia de tabaquismo y/o alcoholismo, la mayoría de ellos muere por progresión de enfermedad y metástasis.

Introduction: carcinomas of the head and neck are relatively common.They include diff erent histological types and present a rangeof clinical characteristics, and are associated with diverse risks of mortality. Objective: To perform a casuistic review of cases of head andneck carcinomas over a period of fi ve years at a State Cancer Center.Material and method: A retrospective study was conducted, in whichrisk factors and treatments were analyzed. Univariate and multivariatestatistical analyses were performed for the purpose of evaluatingprognostic and survival factors. Results: A total of 32 fi les were foundto meet the criteria required by the study. Patient follow-up ranged from2 to 32 months. The predominant histological variant identifi ed wasthe squamous cell carcinoma, while the most common primary treatment was surgery. Conclusions: This study shows that survival fromhead and neck carcinomas decreases in patients who are in advancedclinical stages, particularly those of a certain age with a history ofsmoking and/or alcohol use, most of whom die from the progression and metastasis of the disease.

Evaluación de la enfermedad periodontal e hiperglucemia asociados con diabetes mellitus tipo 2 en pacientes del estado de Durango, México / Evaluation of periodontal disease and hyperglycemia associated to type 2 diabetes mellitus in patients from Durango State, Mexico

Antecedentes: la diabetes mellitus es considerada un problema de salud pública en todo el mundo Este padecimiento afecta órganos y sistemas, incluyendo la cavidad oral; sin embargo, hay pocos informes en la literatura de los efectos de la diabetes mellitus en la cavidad bucal en la población del estado de Durango. Objetivo: El objetivode este estudio fue determinar la asociación de diversas enfermedadesorales, el índice de masa corporal, así como el nivel de glucosa en sangre en pacientes con diabetes mellitus. Material y métodos: Se realizó un estudio de casos y controles para identifi car la prevalencia de las enfermedades orales en individuos con y sin diabetes mellitus.Los sujetos con diabetes mellitus tipo 1 o 2 se definieron como casos y aquellos con otras enfermedades fueron defi nidos como controles. El índice de masa corporal y la concentración de glucosa en sangre fueron evaluados en todos los sujetos. El análisis estadístico incluyólas pruebas chi cuadrada y promedio y desviación estándar de los datos. esultados: Se evaluaron 312 personas, 38 pacientes con diabetes mellitus tipo 1, 79 con diabetes mellitus tipo 2 y 195 sin diabetes mellitus. Diferencias signifi cativas fueron encontradas en individuos con DM2, que mostraron una mayor frecuencia de periodontitis, así como diferencias significativas entre este tipo de diabetes y niveles elevadosde glucosa en sangre...

Background: Diabetes mellitus is considered a public health problem worldwide and one that affects organs and systems alike, including the oral cavity. However, there are few reports in the literature on the effects of diabetes mellitus on the oral cavity of the population in the north of Mexico. Objective: The aim of this study was to determine the link between various oral diseases, body mass index, and blood glucose level in patients with diabetes mellitus. Material and methods:A case-control study was conducted to identify the prevalence of oral diseases in patients with and without diabetes mellitus. Patients with type 1 or type 2 diabetes mellitus were defi ned as cases and patients with other diseases were defi ned as controls. The body mass index and blood glucose concentration of all subjects were measured. Statistical analysis included chi-squared tests, and the average and standard deviation of the data. Results: 312 subjects were assessed: 38 patients with type 1 diabetes mellitus, 79 with type 2 diabetes mellitus, and 195 without diabetes mellitus. Signifi cant differences were found in DM2 patients, who were more likely to exhibit periodontitis and high blood glucose levels. Furthermore, the presence of obesity and hypertension in patients with type 2 diabetes was found to be a risk factor for de-veloping periodontitis...

Expression of the transcription factor PITX2 in ameloblastic carcinoma.

Ameloblastic carcinoma is a rare odontogenic tumour that combines the histological features of ameloblastoma with cytological atypia. Until 2005, the incidence of ameloblastic carcinoma was unknown, and since then, fewer than 60 cases have been reported. These tumours may originate from pre-existing tumours or cysts, or they arise de novo from the activation or transformation of embryological cells. PITX2 is a transcription factor that is a product and regulator of the WNT cell signalling pathway, which has been involved in development of several tumours. To analyse whether PITX2 could be involved in the biological behaviour of ameloblastic carcinoma, we analysed the expression of this transcription factor in a sample of this tumour and nine benign ameloblastomas to compare. The results of Western blotting and RT-PCR analyses were positive, and considering the hundreds of genes that PITX2 regulates, we believe that its expression could be intimately linked to the behaviour of ameloblastic carcinoma and possibly other odontogenic lesions.

Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns.

Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors.

A histopathological and immunohistochemical analysis of ameloblastic fibrodentinoma.

Ameloblastic fibrodentinoma (AFD) is considered a mixed odontogenic tumor that is characterized by conserved epithelial and ectomesenchymal neoplastic components. AFD is composed of long narrow cords and islands of odontogenic epithelium; the epithelial strands lie in a myxoid cell-rich ectomesenchymal tissue with stellate-shaped fibroblasts that exhibit long slender cytoplasmic extensions that resemble dental papilla. The lesions show the presence of dysplastic dentin. Although AFD is a rare entity and its very existence is not completely accepted, based on the extent of histodifferentiation, it is considered to represent a stage between ameloblastic fibroma and ameloblastic fibroodontoma. This study aimed to provide a histopathological and immunohistochemical characterization of this infrequent tumor. A large panel of antibodies including amelogenin, Ck 19, calretinin, syndecan-1, E-cadherin, MSH2, histone H3, and Ki-67 was used to illustrate the nature of the tumor.

Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature.

Papillary thyroid carcinoma is the most common thyroid malignancy, and has an excellent prognosis, even with cervical lymph node metastasis; however, histological variants are considered relevant, which may be associated with familial adenomatous polyposis and tumor aggressiveness. Histological features, such as vascular and/or lymphatic invasion, angiogenesis, multifocality, high cellular proliferation rate, neoplastic cell dissemination, and the histological varieties, are indicative of poor prognosis, together with associated clinical factors: age, sex, and tumor size.