RESUMEN
Skin and soft tissue reconstruction represents one of the most debated issues of plastic surgery. The advent of regenerative medicine has shown new pathways with the use of lipofilling and dermal regeneration templates. The aim of this study was to investigate the histological and clinical modifications occurring after lipofilling in the areas previously reconstructed with Integra® and an autologous thin dermal-epidermal graft. Histological and immunohistochemical analysis were performed on nine patients to compare skin before and after lipofilling. Pre- and post-operative examinations (POSAS, VAS scale) were carried out as well as taking clinical photographs. The authors detected an overall clinical and histological improvement in all cases. Data obtained from POSAS and VAS scale showed a statistically significant (p less than 0.05) improvement concerning all variables investigated before surgery. The biopsies revealed qualitative modifications with hematoxylin-eosin and Masson trichrome stain. Immunohistochemistry with CD31 antibody also demonstrated quantitative changes with an increased number of vessels. The photographs enabled to compare the clinical situation before and after lipofilling with better aesthetic outcomes. Lipofilling gave good functional and aesthetic results in the areas treated with Integra® and autologous thin dermal-epidermal grafts.
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Dermis/fisiología , Procedimientos de Cirugía Plástica , Regeneración , Trasplante de Piel , Adulto , Anciano , Autoinjertos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim of this study was to evaluate the levels of autophagy in oral leukoplakia and squamous cell carcinoma and to correlate with clinical pathological features, as well as, the evolution of these lesions. METHODOLOGY: 7 Normal oral mucosa, 51 oral leukoplakias, and 120 oral squamous cell carcinomas (OSCC) were included in the study. Histological sections of the mucosa and leukoplakias were evaluated throughout their length, while the carcinomas were evaluated using Tissue Microarray. After the immunohistochemical technique, LC3-II positive cells were quantified in the different epithelial layers of the mucosa and leukoplakias and in the microarrays of the squamous cell carcinomas. The correlation between positive cells with the different clinical-pathological variables and with the evolution of the lesions was tested using the t test, ANOVA, and Kaplan-Meier survival analysis. RESULTS: We observed increased levels of autophagy in the oral squamous cell carcinomas (p<0.001) in relation to the other groups, but without any association with poorer evolution or survival of these patients. Among the leukoplakias, we observed a higher percentage of positive cells in the intermediate layer of the dysplastic leukoplakias (p=0.0319) and in the basal layer of lesions with poorer evolution (p=0.0133). CONCLUSION: The levels of autophagy increased during the process of oral carcinogenesis and are correlated with poorer behavior of the leukoplakias.
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Autofagia , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Leucoplasia Bucal/patología , Neoplasias de la Boca/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
The osteogenic transcription factor, Runx2, is abnormally expressed in prostate cancer (PCa) and associated with metastatic disease. During bone development, Runx2 is activated by signals known to be hyperactive in PCa including the RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues including S301 and S319 (equivalent to S294 and S312 in human Runx2). This study examines the role of these phosphorylation sites in PCa. Runx2 was preferentially expressed in more invasive PCa cell lines (PC3>C4-2B>LNCaP). Furthermore, analysis using a P-S319-Runx2-specific antibody revealed that the ratio of P-S319-Runx2/total Runx2 as well as P-ERK/total ERK was highest in PC3 followed by C4-2B and LNCaP cells. These results were confirmed by immunofluorescence confocal microscopy, which showed a higher percentage of PC3 cells staining positive for P-S319-Runx2 relative to C4-2B and LNCaP cells. Phosphorylated Runx2 had an exclusively nuclear localization. When expressed in prostate cell lines, wild-type Runx2 increased metastasis-associated gene expression, in vitro migratory and invasive activity as well as in vivo growth of tumor cell xenografts. In contrast, S301A/S319A phosphorylation site mutations greatly attenuated these Runx2 responses. Analysis of tissue microarrays from 129 patients revealed strong nuclear staining with the P-S319-Runx2 antibody in primary PCas and metastases. P-S319-Runx2 staining was positively correlated with Gleason score and occurrence of lymph node metastases while little or no Runx2 phosphorylation was seen in normal prostate, benign prostate hyperplasia or prostatitis indicating that Runx2 S319 phosphorylation is closely associated with PCa induction and progression towards an aggressive phenotype. These studies establish the importance of Runx2 phosphorylation in prostate tumor growth and highlight its value as a potential diagnostic marker and therapeutic target.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Neoplasias de la Próstata/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Fosforilación/genética , Neoplasias de la Próstata/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Toll-like receptors (TLR) are essential for the innate immune response against invading pathogens and have been described in immunocompetent cells of areas affected by periapical disease. Besides initiating the inflammatory response, they also directly regulate epithelial cell proliferation and survival in a variety of settings. This study evaluates the in situ expression of TLR4 in periapical granulomas (PG) and radicular cysts, focusing on the epithelial compartment. Twenty-one periapical cysts (PC) and 10 PG were analyzed; 7 dentigerous non-inflamed follicular cyst (DC) served as control. TLR4 expression was assessed by immunohistochemistry. TLR4 immunoreaction products were detected in the epithelium of all specimens, with a higher percentage of immunostained cells in PG. Although TLR4 overexpression was detected in both PG and PC, there were differences that seemed to be related to the nature of the lesion, since in PG all epithelial cells of strands, islands and trabeculae were strongly immunoreactive for TLR4, whereas in PC only some areas of the basal and suprabasal epithelial layers were immunostained. This staining pattern is consistent with the action of TLR4: in PG it could promote formation of epithelial cell rests of Malassez and in epithelial strands and islands the enhancement of cell survival, proliferation and migration, whereas in PC TLR4 could protect the lining epithelium from extensive apoptosis. These findings go some way towards answering the intriguing question of why many epithelial strands or islands in PG and the lining epithelium of apical cysts regress after non-surgical endodontic therapy, and suggest that TLR4 plays a key role in the pathobiology of the inflammatory process related to periapical disease.
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Células Epiteliales/metabolismo , Células Epiteliales/patología , Regulación de la Expresión Génica , Quiste Radicular/metabolismo , Quiste Radicular/patología , Receptor Toll-Like 4/biosíntesis , Adulto , Supervivencia Celular , Femenino , Humanos , Inmunohistoquímica/métodos , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Toll-like receptors (TLRs) play an essential role in the activation of innate immunity and they can promote cancer cell survival and tumor progression. It has been claimed that TLRs can somehow predict the clinical behavior in oral squamous cell carcinoma (OSCCs). AIM: To elucidate the molecular basis underlying keratocystic odontogenic tumor (KOCTs) aggressive behavior and recurrence we carried out this immunohistochemical study on TLR3 and TLR4 expression in sporadic primary KCOTs (sp-KCOTs), sporadic recurrent KCOTs (sp-KCOTs), and NBCCS-associated KCOTs (NBCCS-KCOTs). METHOD: 40 cases of KOCTs removed from 23 men and 17 women were the sample. Paraffin-embedded blocks were processed for immunohistochemistry. Sections were incubated with TLR3 and TLR4 antibodies and immunoreactivity evaluated on a semi-quantitative score. RESULTS: Both TLR3 and TLR4 were expressed in KCOTs epithelium, although with a different extent. TLR3 was not expressed in sp-KCOTs and sr-KCOTs, but it showed a faint staining in NBCCS-KCOTs. On the other hand, both cytoplasmic and nuclear staining for TLR4 was detected in all the 3 types of lesions; however being significantly more expressed in sr-KCOT and NBCCS-KCOTs (p < 0.0001). Our results, demonstrated an association between TLR4, but not TLR3 expression to recurrence behavior of KCOTs. In fact, TLR4 was up-regulated in sr-KCOTs and NBCCS-KCOTs but not in sp-KCOTs. CONCLUSIONS: According these findings it seems conceivable to assume that the up-regulation of TLR4 in some KCOTs can be correlated somehow to their tendency recurrence.
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Síndrome del Nevo Basocelular/inmunología , Recurrencia Local de Neoplasia/inmunología , Tumores Odontogénicos/inmunología , Receptor Toll-Like 3/análisis , Receptor Toll-Like 4/análisis , Adolescente , Adulto , Síndrome del Nevo Basocelular/patología , Núcleo Celular/química , Núcleo Celular/inmunología , Núcleo Celular/patología , Citoplasma/química , Citoplasma/inmunología , Citoplasma/patología , Epitelio/química , Epitelio/inmunología , Epitelio/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/química , Recurrencia Local de Neoplasia/patología , Tumores Odontogénicos/química , Tumores Odontogénicos/patología , Adulto JovenRESUMEN
BACKGROUND: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. METHODS: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. RESULTS: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. CONCLUSION: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.
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Biomarcadores de Tumor/genética , Cadherinas/genética , Carcinoma de Células Escamosas/genética , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de la Boca/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Antimetabolitos Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Metilación de ADN/efectos de los fármacos , Metilasas de Modificación del ADN/antagonistas & inhibidores , Metilasas de Modificación del ADN/metabolismo , Regulación hacia Abajo , Inhibidores Enzimáticos/farmacología , Epigénesis Genética/efectos de los fármacos , Receptores ErbB/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Pronóstico , Regiones Promotoras Genéticas , Transporte de Proteínas , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de TiempoRESUMEN
Poly(ADP-ribose) polymerase (PARP) is a 116kDa enzyme catalysing the synthesis of ADP-ribose polymers from NAD+. PARP is activated in response to DNA strand breaks and plays a critical role in the maintenance of genomic integrity. However, considering its role also in transcription, proliferation as well as apoptosis in biological process, in the present study the role of PARP in bone regeneration was evaluated, in particular in bone cell proliferation and differentiation processes. Thus, formalin fixed paraffin embedded specimens of 10 human bone samples after sinus lift were collected and investigated by immunohistochemistry using a mouse monoclonal anti-human PARP antibody. PARP was expressed in cells with morphological features of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid tissue and bone. Few osteoclasts were observed and showed only focal nuclear expression of PARP, while osteocytes showed no positivity for PARP. Our data showed an overall involvement of PARP enzyme in human bone tissues, in particular during bone regeneration process.
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Regeneración Ósea , Poli(ADP-Ribosa) Polimerasas/análisis , Apoptosis , Diferenciación Celular , Proliferación Celular , Humanos , Osteoblastos/enzimología , Poli(ADP-Ribosa) Polimerasas/fisiología , Antígeno Nuclear de Célula en Proliferación/análisisRESUMEN
AIM: To determine the epithelial expression of ß-catenin and survivin in sporadic (primary, and recurrent) and nevoid basal cell carcinoma syndrome (NBCCS) keratocystic odontogenic tumour (KCOT) in order to assess activation of the ß-catenin pathway and evidence of apoptotic inhibition, processes that may contribute to the known differences in their biological behaviour. MATERIALS AND METHODS: Sections from 40 cases of KCOT (19 sporadic/primary; 9 sporadic/recurrent and 12 NBCCS-associated) were immunohistochemically stained for ß-catenin and survivin. The extent and intensity of immunoreactivity within the lining epithelium was assessed, using semi-quantitative scales, independently by two pathologists who were blinded to the clinical-pathological data. Data were analysed using Kruskal-Wallis test and, for pair-wise comparisons, Mann-Whitney test with Bonferroni correction. RESULTS: All cystic epithelial linings stained for ß-catenin and survivin but there were differences in the pattern and intensity of staining among KCOT types. Sporadic primary KCOT showed weaker staining for ß-catenin (P=0.0003) and survivin (P<0.0048) that was restricted to the basal and para-basal layers only, compared to sporadic recurrent and NBCCS-associated KCOT, which showed expression throughout all epithelial layers. There were no differences in ß-catenin expression among recurrent and NBCCS-associated KCOT, whereas the intensity of survivin staining was higher in NBCCS-KCOT (P=0.0003). Nuclear staining for ß-catenin was found exclusively in recurrent (5/9 cases) and NBCCS-associated (4/12 cases) KCOT. CONCLUSION: The data demonstrate ß-catenin delocalization and survivin over-expression in recurrent sporadic and NBCCS-associated KCOT suggesting that these pathways related to apoptotic inhibition have a role in KCOT growth and recurrence.
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Síndrome del Nevo Basocelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis/metabolismo , Tumores Odontogénicos/metabolismo , beta Catenina/metabolismo , Adolescente , Adulto , Apoptosis , Ciclo Celular , Femenino , Humanos , Inmunohistoquímica , Queratinas/química , Masculino , Persona de Mediana Edad , Recurrencia , Survivin , Adulto JovenRESUMEN
Beta-catenin is a major protein in the Wnt signalling pathway. Although it has been studied in various types of carcinoma, little is known about its expression in mesenchymal tumours. In this study 41 specimens of a variety of mesenchymal childhood tumours were compared to 24 samples of the corresponding adult tumours to assess the diagnostic value of nuclear ß-catenin expression using tissue microarray-based immunohistochemistry. Similar to adult sarcoma and fibromatosis, ß-catenin was not expressed in the majority of childhood sarcomas, and its nuclear translocation was detected in paediatric fibromatosis; non-negligible levels of nuclear staining in other tumour types demonstrate Wnt pathway activation in mesenchymal neoplasms of childhood and adolescence.
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Regulación de la Expresión Génica , Inmunohistoquímica , Mesodermo/patología , Sarcoma/patología , beta Catenina/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estándares de Referencia , Análisis de Matrices Tisulares , beta Catenina/genéticaRESUMEN
BACKGROUND: N-Cadherin (CDH2) is a calcium-dependent adhesion protein, whose de novo expression, re-expression, up-regulation and down-regulation in human tumors has been demonstrated. The aim of the present work was to define the prognostic role of N-Cadherin in a large series of oral squamous cell carcinomas (OSCCs). MATERIALS AND METHODS: A total of 94 selected OSCCs were quantitatively and qualitatively analyzed by immunohistochemistry for N-Cadherin. The association between protein expression and clinico-pathological parameters was assessed by statistical analysis. RESULTS: In neoplastic tissue, N-Cadherin levels were more evident than in normal peritumoral epithelium (p<0.05). Protein staining was mainly detected in the neoplastic cells, and only focal nuclear positivity was observed. Expression of cytoplasmic N-Cadherin correlated significantly with poor histological differentiation (p<0.05). Furthermore, we have observed significant a statistical trend for stage and a correlation with worst patient outcome, also confirmed by Kaplan-Meier estimates. CONCLUSION: Our work has underlined the key-role of N-Cadherin in oral carcinogenesis and in the prognostic stratification of patients.
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Cadherinas/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Oncología Médica/métodos , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , PronósticoRESUMEN
Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.
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Carcinoma de Células Escamosas/virología , Neoplasias de la Boca/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , ADN Viral/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Papillomaviridae/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genéticaRESUMEN
The aim of this study is to investigate the expression of the chromosomal passenger protein Aurora B and its activated (phosphorylated) form in a large series of human oral squamous cell cancers (OSCC) and to evaluate its clinical and prognostic significance. Western blotting analysis revealed overexpression of both Aurora B and Thr-232 Phopsho-Aurora B in OSCC lines as compared to normal keratinocytes and bladder cancer cells. Furthermore, protein expression was analysed by immunohistochemistry in 101 OSCC of different site, stage and histological grade and in normal peritumoural areas. The intracellular localization of Aurora B in tumour cells was mainly nuclear, especially in proliferative areas, and significant overexpression was found in tumours in comparison to normal peritumoural areas (P=0.012). Staining results were correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and tumour stage (stage II, III and IV vs stage I, P=0.030) and size (<2cm vs >2cm, P=0.010). Cox regression analysis confirmed a poorer disease-free survival in cases with high expression of Aurora B protein. Kaplan-Meier curves showed shorter time to progression in patients with high levels of Aurora B expression (p<0.05). Moreover, the tumoral group with nuclear Aurora B immunolocalization had the worst prognosis (P=0.0364 in disease free survival). Our results suggest that assessing Aurora B expression might help in patients risk stratification and serve as a novel therapeutic target in advanced OSCCs.
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Carcinoma de Células Escamosas/enzimología , Neoplasias de la Boca/enzimología , Proteínas Serina-Treonina Quinasas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Aurora Quinasa B , Aurora Quinasas , Western Blotting , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Neoplasias de la Boca/terapia , Pronóstico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidoresRESUMEN
Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2) )/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells.
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Receptores de Esteroides/metabolismo , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Familia-src Quinasas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Niño , Preescolar , Progresión de la Enfermedad , Receptores ErbB/metabolismo , Estradiol/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Masculino , Metribolona/farmacología , Persona de Mediana Edad , Proyectos Piloto , Transducción de Señal , Adulto JovenRESUMEN
Verrucous carcinoma (also known as Ackerman tumor) is an uncommon exophytic low-grade well-differentiated variant of squamous cell carcinoma. This neoplasm typically involves the oral cavity, larynx, genitalia, skin, and esophagus. It is well known for its locally aggressiveness and for its clinically slow-growing behaviour with minimal metastatic potential. Verrucous carcinoma of oral cavity is so closely aligned with the use of snuff and chewing tobacco that it has been called the "snuff dipper's cancer". Recent studies have proved the role of HPV. The typical clinical presentation of oral verrucous carcinoma has long been known, as its remarkably innocuous appearance and biological behaviour. In this work, we report a review of the scientific literature and describe a troublesome case of oral verrucous cancer.
RESUMEN
Epigenetic DNA methylations plays an important role in oral carcinogenesis. The soluble frizzled receptor protein (SFRP) family together with WIF-1 and DKK-3 encodes antagonists of the WNT pathway. Silencing of these genes leads to constitutive WNT signalling. Because aberrant expression of beta-catenin might be associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a collection of primary OSCC with matched normal oral mucosa, the methylation status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3, that are involved directly and indirectly in WNT pathway, in order to demonstrate WNT-pathway activation in the absence of beta-catenin and/or APC/Axin mutations during oral carcinogenesis. Methylation-specific PCR (MSP) was performed to study inactivation of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes in 37 cases of paraffin embedded oral cancer. This study showed that the methylation is an important epigenetic alteration in oral cancer. In particular, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 revealed methylation status of their promoter in OSCC, whereas SFRP-1 showed demethylation in cancer. Fisher's exact test revealed statistically significant results (p<0.05) for all genes. The Wald test confirmed the statistically significant association between SFRP2-4-5 gene methylation and OSCC (p<0.05). SFRP-1 was also characterized by a different statistically significant epigenetic behaviour, because of it was demethylated in cancer (p<0.05). Statistical regression test showed high levels of sensitivity, specificity and accuracy for SFRP genes, while WIF-1 and DKK-3 have reportedly high specificity, moderate accuracy but low sensitivity. This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP, WIF-1 and DKK-3 genes.
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Carcinoma de Células Escamosas/genética , Metilación de ADN/genética , Epigénesis Genética , Neoplasias de la Boca/genética , Transducción de Señal/genética , Proteínas Wnt/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/metabolismo , Quimiocinas , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Curva ROC , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Sensibilidad y Especificidad , Proteínas Wnt/metabolismoRESUMEN
Human papilloma virus infection is thought to play a role in laryngeal carcinogenesis; the variable association reported in literature may be due to wide range of HPV genotypes. We report the case of a 51-year-old man affected by laryngeal squamous cell carcinoma; analysis of DNA extracted by cancer cells by an innovative molecular virology assay (INNO-LiPA HPV Genotyping Extra) showed the presence of two high-risk HPV genotypes, HPV-73 and -82. Immunohistochemical examination confirmed positivity for both capsid protein and viral oncogenic protein E7. Such association has never been reported in literature so far, and a brief discussion on the importance of assessing HPV status in laryngeal cancer is provided.
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Carcinoma de Células Escamosas/virología , Neoplasias Laríngeas/virología , Papillomaviridae/clasificación , Infecciones por Papillomavirus/virología , Biopsia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Sondas de ADN de HPV , Genotipo , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Laringectomía , Laringe/patología , Laringe/virología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Disección del Cuello , Estadificación de Neoplasias , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/cirugía , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE OF INVESTIGATION: aberrant gene function and transcriptional silencing by CpG island hypermethylation have become a critical component in the initiation and progression of endometrial cancer. The aim of this study was to investigate the methylation status of genes associated with aberrant DNA hypermethylation in benign, premalignant and malignant endometrial lesions. METHODS: using nested methylation-specific PCR, we assessed the methylation of the promoter regions of two genes, hMLH1 and CDKN2A/p16, in tissue samples from endometrial polyps (EP), atypical hyperplasia (AH) and endometrial cancer (EC). RESULTS: the promoter region of at least one of the two genes was aberrantly methylated in EP (hMLH1 42%, CDKN2A/p16 16%), AH (hMLH1 16%, CDKN2A/p16 50%), EC (hMLH1 50%, CDKN2A/p16 75%). Interestingly, hypermethylation of both genes was found with significant increased frequence in AH and EC, but not in benign lesions. CONCLUSIONS: our preliminary findings seem to suggest that the association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions; this further supports the hypothesis that methylation of such DNA mismatch repair and tumour-suppressor genes may be associated with endometrial carcinogenesis thus representing a valuable target for selective pharmacologic therapy.
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Proteínas Adaptadoras Transductoras de Señales/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilación de ADN , Neoplasias Endometriales/genética , Proteínas Nucleares/genética , Lesiones Precancerosas/genética , Enfermedades Uterinas/genética , Adulto , Anciano , Reparación de la Incompatibilidad de ADN , Femenino , Humanos , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Pólipos/genética , Regiones Promotoras Genéticas/genéticaRESUMEN
Metastatic tumours to the oral region are rare, and those reported in the buccal soft tissues are even less frequent. We describe a case of anaplastic carcinoma of the lung in a 60-year-old man, presenting a huge oral metastasis as the first sign of his primitive lung malignancy. Clinically, the oral lesion mimicked a high-grade primitive carcinoma of the oral cavity. The biopsy established the gingival metastasis from lung cancer which was confirmed by a fine-needle aspiration cytology examination. We report an uncommon case of metastatic lung carcinoma to the gingiva emphasizing the differential diagnosis between primary and metastatic tumours; a short discussion on the pathways of metastatization to oral cavity soft tissues, as well as brief review of the literature are also presented.
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Carcinoma/prevención & control , Neoplasias Pulmonares/patología , Neoplasias de la Boca/secundario , Neoplasias de los Tejidos Blandos/secundario , Carcinoma/patología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
Discoid Lupus Erythematosus (DLE) is a chronic disease with a typical cutaneous involvement. This pathology rarely involves mucosa: oral cavity is interested in 20 percent of DLE patients. We describe a case of oral DLE in a 50-year-old woman with an anamnesis for autoimmune disorders. This study shows the helpful role of immunofluorescence in the diagnosis of autoimmune diseases. The first diagnostic step was the clinical observation of the oral mucosa: the lesion area was erythematous, atrophic and hyperkeratotic. The patient then underwent laboratory examination. We utilized human epithelial cells (Hep-2010) for Indirect Immuno-Fluorescence (IIF). Moreover, the biopsy site for Direct Immuno-Fluorescence (DIF) and histopathological analysis was the untreated oral lesion. IIF detected an increase of Anti-Nuclear Antibody (ANA) and positivity for SSA-RO. By DIF, we observed IgG/IgA/fibrinogen along basal layer. Multiple biopsies reported signs of chronic basal damage. Steroid systemic therapy induced a considerable lesion regression. We suggest the use of immunofluorescence with the integration of further data to improve diagnosis of rare diseases and to establish a suitable therapy.
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Lupus Eritematoso Discoide/diagnóstico , Mucosa Bucal , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/aislamiento & purificación , Femenino , Fibrinógeno/inmunología , Fibrinógeno/aislamiento & purificación , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulinas/inmunología , Inmunoglobulinas/aislamiento & purificación , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Discoide/patología , Persona de Mediana Edad , Mucosa Bucal/inmunología , Mucosa Bucal/patología , Ribonucleoproteínas/inmunología , Ribonucleoproteínas/aislamiento & purificaciónRESUMEN
COX-2 expression in tumour cells has been associated with carcinogenesis in many human neoplasms, including head and neck cancer, while the COX-1 isoform of the cyclooxygenase enzyme is constitutively expressed in normal tissues. We measured COX-1 and COX-2 m-RNA expression in samples of both oral cancer and matched oral mucosa from 22 patients by RealTime RT-PCR; clinic pathological data (grading, TNM staging, inflammation, follow-up) of all patients were available for statistical evaluation. Most of the tumor samples in our study expressed at least one cyclooxygenase enzyme (COX-1 or COX-2 mRNA) more than their matched normal oral mucosa (p<0.05), with no correlation with the entity of inflammation, and a significant inverse relationship was found between COX-1 and COX-2 in each sample. Higher levels of COX-2 expression were associated with poor disease-free survival (p<0.05), but not with overall survival and higher tumor stage and grade. Our results suggest that COX-1 may play a role in oral carcinogenesis, and could be regarded as a potential therapeutic target by chemo preventive drugs; moreover, COX-2 expression might be addressed as a new prognostic tool in the clinical management of OSCC.