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The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.
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Adenoma Pleomorfo , Carcinoma Adenoide Cístico , Humanos , Ciclo Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de ZesteRESUMO
Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Emetina/metabolismo , Emetina/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Histonas/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Células-Tronco Neoplásicas/patologia , Sirtuína 1/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.
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Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) leading to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the population of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concentrations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells.
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OBJECTIVE: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K-AKT-mTOR) signaling pathway is an important regulator of cell proliferation, survival, and motility. The gain or loss of function of proteins related to this pathway results in the neoplastic transformation in several types of cancers. This study aimed to evaluate the expression profile of the PI3K-AKT-mTOR pathway in patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines. STUDY DESIGN: The study involved 26 formalin-fixed paraffin-embedded tissue samples from patients with HNSCC. The analysis of immunohistochemical expression of PI3K, AKT, p-mTOR, and phosphatase and tensin homolog (PTEN) proteins was performed by a quantitative assessment. The in vitro gene and protein expression evaluation was performed by real-time polymerase chain reaction and Western blot assay, respectively, in the human cell lines SCC-9 and FaDu. RESULTS: High levels of PI3K, AKT, and p-mTOR were found in most HNSCC tumors. Following this result, we observed low amounts or absence of PTEN in most samples. Additionally, the FaDu cells (pharynx) showed higher AKT expression but lower expression of p-mTOR compared with SCC-9 cells (oral cavity), which hints at a loco-anatomical relevance. CONCLUSION: Overall, this study found increased expression of the PI3K-AKT-mTOR pathway along with evident PTEN reduction in head and neck cancer.
Assuntos
Neoplasias de Cabeça e Pescoço , Fosfatidilinositol 3-Quinases , Brasil , Linhagem Celular Tumoral , Proliferação de Células , Humanos , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Epithelial to mesenchymal transition promotes cell adhesion loss, enabling invasion and metastasis. MicroRNAs are a class of small non-codifying RNAs that regulate gene expression. OBJECTIVES: The aim of this study was to evaluate the expression of microRNAs that could regulate the expression of EMT factors in salivary gland tumors (SGTs). METHODS AND RESULTS: The expression of microRNAs miR-9, miR-34a, miR-101, miR-138, miR-155, and miR-200c-described in the literature to target EMT factors-was evaluated by Real-time RT-PCR (qPCR) in pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) samples. Bioinformatics tools were applied to identify miR targets and immunohistochemistry was used to examine the expression of the proteins E-cadherin, Twist, ZEB-1, ß-Catenin, and c-Kit. Comparing miR expression among SGT types, we observed increased expression of miR-9, and miR-138 in PAs, and increased miR-155 expression in MECs. Low-grade MECs exhibited increased miR-155 expression (p = 0.032). MECs that generated lymph node metastases had increased miR-200c levels (p = 0.018). MECs tended to have decreased expression of EMT-related proteins when compared to the other SGT types (c-Kit p < 0.001, Twist p = 0.014, and ZEB p = 0.012). Notably, increased c-Kit expression was associated with the presence of perineural infiltration in ACC (p = 0.050). CONCLUSIONS: This study provides evidence of alterations in the expression of EMT-factors regulating miRs, especially of miR-9, miR-138, miR-155, and miR-200c. No significant relationships were found between the expression of these miRs and proteins associated with EMT in SGTs.
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MicroRNAs , Neoplasias das Glândulas Salivares , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias das Glândulas Salivares/genéticaRESUMO
A systematic review (SR) and meta-analysis were conducted to determine the prevalence of PI3K-AKT-mTOR signaling pathway mutations in patients with head and neck cancer (HNC). Overall, 105 studies comprising 8630 patients and 1306 mutations were selected. The estimated mutations prevalence was 13 % for PIK3CA (95 % confidence interval [CI] = 11-14; I2 = 82 %; p < 0.0001), 4% for PTEN (95 % CI = 3-5; I2 = 55 %; p < 0.0001), 3% for MTOR (95 % CI = 2-4; I2 = 5%; p = 0.40), and 2% for AKT (95 % CI = 1-2; I2 = 50 %; p = 0.0001). We further stratified the available data of the participants according to risk factors and tumor characteristics, including HPV infection, tobacco use, alcohol exposure, TNM stage, and histological tumor differentiation, and performed subgroup analysis. We identified significant associations between PI3K-AKT-mTOR pathway-associated mutations and advanced TNM stage (odds ratio [OR] = 0.20; 95 % CI = 0.09-0.44; I² = 71 %; p = 0.0001) and oropharyngeal HPV-positive tumors and PIK3CA mutations (OR = 17.48; 95 % CI = 4.20-72.76; I² = 69 %; p < 0.0002). No associations were found between alcohol and tobacco exposure, and tumor differentiation grade. This SR demonstrated that the PI3K-AKT-mTOR pathway emerges as a potential prognostic factor and could offer a molecular basis for future studies on therapeutic targeting in HNC patients.
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Neoplasias de Cabeça e Pescoço , Fosfatidilinositol 3-Quinases , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/genética , Humanos , Mutação , Fosfatidilinositol 3-Quinases/genética , Prevalência , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genéticaRESUMO
Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC.
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Carcinoma de Células Escamosas/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Complexo Repressor Polycomb 1/análise , Adulto , Idoso , Análise de Variância , Carcinogênese/patologia , Estudos de Casos e Controles , Proliferação de Células , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Valores de Referência , Fatores de Risco , Estatísticas não Paramétricas , Carga TumoralRESUMO
Abstract Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC.
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Humanos , Animais , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Antígeno Ki-67/análise , Complexo Repressor Polycomb 1/análise , Mucosa Bucal/patologia , Imuno-Histoquímica , Estudos Transversais , Fatores de Risco , Estatísticas não Paramétricas , Progressão da Doença , Proliferação de Células , Carcinogênese/patologiaRESUMO
BACKGROUND: Epigenetic changes refer to any heritable modification in gene expression independent of alterations in the DNA sequence. Currently, it is well established that epigenetics represents a crucial player for tumor development. Nevertheless, the epigenetic mechanisms involved in the development and progression of salivary gland tumors (SGTs) remain poorly understood. METHODS: In this study, we analyzed the pattern of acetyl-histone H3 (lys9) expression in benign and malignant SGTs and further correlate our results with tumors' proliferative activity and clinical outcomes. We assembled tissue microarrays (TMAs) of 84 cases of SGTs and analyzed for acetyl-histone H3 (lys9) and Ki-67 using immunohistochemistry. The study comprised 42 benign and 42 malignant SGTs. RESULTS: All cases included in this study were positive to acetyl-H3 (lys9). We observed that malignant SGTs were hypoacetylated compared with benign (P = 0.04). Moreover, acetyl-H3 (lys9) expression was inversely correlated with Ki67 (**P = 0.02). CONCLUSION: This study provides the first insight regarding histone modifications in SGTs. Our results suggest that epigenetic mechanism, particularly hypoacetylation of histone H3 (lys9), might play a role in the behavior of salivary gland tumors. Also, our findings suggest that interfering with the acetylation pattern of tumor histones represents a potential novel therapeutic strategy for the treatment of SGTs.
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Cromatina/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Acetilação , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Several mTOR pathway proteins are involved in the regulation of cellular anabolism, growth, proliferation, and survival. Activated proteins in the mTOR pathway are deregulated in multiple types of cancers and could influence prognosis. However, it is unclear whether deregulation of mTOR pathway proteins serves a prognostic role in patients with head and neck cancer (HNC). Furthermore, proteins in the mTOR pathway may be important targets for anticancer therapy. The aim of this study was to summarize existing cohort studies to determine whether immunoexpression of mTOR pathway proteins are important prognostic factors for survival in patients with HNC. MATERIALS AND METHODS: A systematic review was performed using the Cochrane, Lilacs, PubMed, ScienceDirect, Scopus, and Web of Science databases (up to 23 January 2015). A meta-analysis was conducted to measure the frequency of protein expression in head and neck cancer patient samples and the prognostic value of mTOR pathway proteins for overall survival (OS) and disease-free survival (DFS). RESULTS: Twelve studies were included in our final analysis. The meta-analysis revealed that the frequency of overall expression of mTOR pathway proteins was 74.42% (CI: 63.3 to 84.0, P < 0.001, n = 2016 samples). The survival meta-analysis showed a pooled hazard ratio for OS and DFS of 1.44 (95% confidence interval [95% CI] 1.14-1.73) and 1.18 (95% CI 0.71-1.64), respectively. CONCLUSION: This systematic review and meta-analysis support evidence that mTOR pathway proteins can be used as predictive markers for survival in patients with HNC because their expression was significantly associated with poor OS and short DFS.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/imunologia , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Redes e Vias Metabólicas , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Serina-Treonina Quinases TOR/biossíntese , Serina-Treonina Quinases TOR/imunologiaRESUMO
OBJECTIVE: The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters. STUDY DESIGN: We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed. RESULTS: Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001). CONCLUSIONS: The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.
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Adenoma Pleomorfo/imunologia , Carcinoma Adenoide Cístico/imunologia , Carcinoma Mucoepidermoide/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Neoplasias das Glândulas Salivares/imunologia , Biomarcadores Tumorais/imunologia , Fator de Crescimento de Hepatócito/imunologia , Humanos , Imuno-Histoquímica , Análise em Microsséries , Fosforilação , Transdução de SinaisRESUMO
Laser phototherapy (LPT) is widely used in clinical practice to accelerate healing. Although the use of LPT has advantages, the molecular mechanisms involved in the process of accelerated healing and the safety concerns associated with LPT are still poorly understood. We investigated the physiological effects of LPT irradiation on the production and accumulation of reactive oxygen species (ROS), genomic instability, and deoxyribose nucleic acid (DNA) damage in human epithelial cells. In contrast to a high energy density (20 J/cm²), laser administered at a low energy density (4 J/cm²) resulted in the accumulation of ROS. Interestingly, 4 J/cm² of LPT did not induce DNA damage, genomic instability, or nuclear influx of the BRCA1 DNA damage repair protein, a known genome protective molecule that actively participates in DNA repair. Our results suggest that administration of low energy densities of LPT induces the accumulation of safe levels of ROS, which may explain the accelerated healing results observed in patients. These findings indicate that epithelial cells have an endowed molecular circuitry that responds to LPT by physiologically inducing accumulation of ROS, which triggers accelerated healing. Importantly, our results suggest that low energy densities of LPT can serve as a safe therapy to accelerate epithelial healing.
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Quebras de DNA de Cadeia Dupla/efeitos da radiação , Células Epiteliais/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Espécies Reativas de Oxigênio/metabolismo , Proteína BRCA1/análise , Proteína BRCA1/metabolismo , Linhagem Celular , Reparo do DNA , Células Epiteliais/metabolismo , Histonas/análise , Histonas/metabolismo , Humanos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/efeitos da radiaçãoRESUMO
The aim of the present prospective study was to evaluate the impact of laser phototherapy (LPT) on the healing of oral ulcers. Different power densities were used on oral wounds in Wistar rats (n=72) randomly divided into three groups: control (0 J/cm2), 4 J/cm2 laser, and 20 J/cm2 laser. Ulcers (3 mm in diameter) were made on the dorsum of the tongue with a punch. Irradiation with an indium-gallium-aluminum-phosphide laser (660 nm; output power: 40 mW; spot size: 0.04 cm2) was performed once a day in close contact with the ulcer for 14 consecutive days. A statistically significant acceleration in healing time was found with wounds treated with 4 J/cm2 LPT. Moreover, striking differences were found in the ulcer area, healing percentage, degree of reepithelialization, and collagen deposition. The most significant changes occurred after 5 days of irradiation. Based on the conditions employed in the present study, LPT is capable of accelerating the oral mucosa wound-healing process. Moreover, faster and more organized reepithelialization and tissue healing of the oral mucosa were achieved with an energy density of 4 J/cm2 in comparison to 20 J/cm2.
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Lasers Semicondutores , Terapia com Luz de Baixa Intensidade/métodos , Úlceras Orais/terapia , Reepitelização/efeitos da radiação , Animais , Inflamação/patologia , Masculino , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Úlceras Orais/patologia , Estudos Prospectivos , Ratos , Ratos WistarRESUMO
o carcinoma epidermóide bucal é uma doença genética que faz uso de diversos mecanismos de sinalização molecular para crescer, invadir e metastatizar. Profundas alterações genéticas e protéicas podem ser observadas durante este processo que implicam não somente na sinalização intracelular, como em uma intensa comunicação entre as células neoplásicas e modulação do meio ambiente num processo conhecido como sinalização parácrina e autócrina. A presença dos altos níveis de expressão de NFKB nas linhagens de carcinomas epidermóides bucais foi demonstrada, assim como a direta correlação entre esta superexpressão e o aumento na ativação de IL6. A capacidade da via de sinalização do NFKB em estabelecer uma sinalização parácrina diretamente através da IL6 foi provada com a ativação do STAT3 em células epiteliais normais. Fazendo uso da técnica de microarray diversos genes conhecidamente associados a esta via de sinalização assim como genes totalmente desconhecidos foram apontados
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Carcinoma de Células Escamosas , Patologia BucalRESUMO
PTEN is a tumor suppressor gene that encodes a dual phosphatase protein capable of modulating membrane receptors and interaction of the cell and extracellular stimuli. PTEN regulates cell physiology such as division, differentiation/apoptosis and also migration and adhesion. The expression of PTEN was evaluated by immunohistochemistry in OSCC and compared to a well-established histological malignancy grading system. The well-differentiated OSCC were 59.1% and poorly differentiated were 40.9%. According to PTEN expression, the cases were 45.5% positive (the entire tumor showed stained), 22.7% mixed (both negative and positive cells were present) and 31.8% negative (no staining was seen in the tumor cells). PTEN expression in OSCC was related to the malignancy grade (P < 0.0005). Aggressive tumors with a high score of malignancy did not express PTEN, and clearly, the PTEN expression was present in the epithelium adjacent to the tumor. Negative cells were in the invasion border of the tumor. This result suggests that PTEN is related to histologic pattern and biological behavior of OSCC and may be a used as a prognostic marker in the future. The role of PTEN during carcinogenesis and as a biomarker should be further investigated.