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BACKGROUND: The purpose of this pilot study was to evaluate for the first time the effect of 75/25 w/w nano-Hydroxyapatite/Chitosan (nHAp/CS) scaffolds on Guided Bone Regeneration (GBR) in rat calvarial critical-sized defects (CSDs). MATERIAL AND METHODS: Six adult Sprague Dawley rats, 3 males and 3 females, were used. Two CSDs, full thickness and 5mm in diameter, were trephined in both sides of the parietal bone. The right CSD was filled with nHAp/CS scaffold, while the left CSD remained empty, as the control group. The wound was sutured in layers. Rats were euthanized with diethyl ether inhalation at 2, 4 and 8 weeks after surgical procedure. Histological and histomorphometric analysis was performed within distinct regions of interest (ROI): the lateral area inward of the middle sagittal seam; the lateral area outward of the middle sagittal seam and the central area. RESULTS: The mean surface of newly formed bone (in µm2) in the lateral area inward of the middle sagittal seam of all rats was significantly higher (P=0.039) in the experimental group (91733.00±38855.60) than the control group (46762.17±25507.97). The NOex-c, defined as total number of osteocytes (OST) in newly formed bone surface in experimental group [experimental OST] minus the total number of osteocytes in newly formed bone surface in control group [control OST], was significantly greater (P=0.029) at 4th week post-surgery. Within the experimental group, a statistically significant increase (P=0.042) in the surface of newly formed bone was noticed in rats euthanized in 4th week compared with rats euthanized in 2nd week after surgery in the lateral area inward of the middle sagittal seam. CONCLUSIONS: The results of this study suggest that 75/25 w/w nHAp/CS scaffolds should be considered as a suitable biomaterial for GBR.
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Materiales Biocompatibles/farmacología , Desarrollo Óseo/efectos de los fármacos , Quitosano/farmacología , Hidroxiapatitas/farmacología , Nanopartículas , Cráneo/cirugía , Andamios del Tejido , Animales , Femenino , Masculino , Proyectos Piloto , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Matrix metalloproteinases (MMPs) is a superfamily of proteins involved in angiogenesis and metastatic tissue invasion in many cancers. Overexpression of MMP- 9 has been detected in significant proportions of laryngeal squamous cell carcinomas (LSCCs), but its prognostic impact remains unclear. In this study we performed a digital image analysis for analyzing MMP-9 protein expression in a series of LSCCs correlating them with clinicopathological factors. METHODS: MMP-9 protein expression level was determined immunohistochemically in 30 tissue sections surgically derived from patients (21 male and 9 female) with LSCC. Using digital image analysis, we measured their corresponding protein expression levels (staining intensity/S.I. range values 0-255). RESULTS: Moderate and high MMP-9 protein expression levels (grouping as 2+/3+ overexpression) were detected in 19/30 (63.3%) cases. Statistical significance was observed correlating stage with SI (p=0.02), whereas a borderline association with differentiation grade of the examined tumors was also registered (p=0.05). Interestingly, high levels of MMP-9 expression were observed in cases that demonstrated a significant level of inflammatory (predominantly lymphocytic) infiltration. CONCLUSION: MMP-9 protein overactivation is a frequent and significant genetic event in LSCC, correlating with its biological behavior (increased TNM stage). MMP-9 seems to mediate an epithelial-stromal intra-reaction correlating also with induction of specific inflammation pathways.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/enzimología , Neoplasias de Cabeza y Cuello/enzimología , Neoplasias Laríngeas/enzimología , Metaloproteinasa 9 de la Matriz/análisis , Anciano , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Distribución de Chi-Cuadrado , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Regulación hacia ArribaRESUMEN
PURPOSE: To evaluate the HER-2/neu expression and its relationship with clinicopathological parameters and prognosis in colorectal cancer patients. METHODS: A total of 51 colorectal cancer patients who underwent resection with curative intent from January 2005 to March 2006 were included in this study. Patients were regularly followed up and survival data were obtained as of as April 2011. HER-2/neu protein expression was evaluated from tissue samples from the primary tumor using a semiquantitative standardized immunohistochemical staining kit. Staining intensity was scored as faint (1+), weak to moderate (2+) and moderate to strong (3+). RESULTS: Forty-nine (96.1%) patients showed 1+ staining, 2 (3.9%) 2+, while no case was strongly positive (3+) for HER-2/neu. No apparent association was noted between HER-2/neu expression and patients' age, gender, tumor location, tumor grade, stage and survival. CONCLUSION: Moderate (2+) overexpression of HER-2/neu was detected in a small proportion of colorectal cancer patients. Considering the low rate of HER-2/neu overexpression in colorectal cancer, studies with larger sample sizes using standardized tests are essential to understanding the biologic role of HER-2/neu in this disease.
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Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/enzimología , Receptor ErbB-2/análisis , Anciano , Colectomía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
PURPOSE: c-MYC oncogene is frequently deregulated by amplification in colon adenocarcinoma. c-MYC also activates telomerase by inducing expression of its catalytic subunit (h-TERT). Furthermore, telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. Our aim was to evaluate the significance of c-MYC and h-TERT co-expression in colon adenocarcinoma. METHODS: Sixty paraffin embedded primary colon adenocarcinomas were cored at 1.5 mm diameter and transferred to one microarray block. Immunohistochemistry was performed using anti-h-TERT, and c - MYC antibodies. A quantitative digitized macro was performed to evaluate their expression. RESULTS: c-MYC and h-TERT overexpression was observed in 27 (45%) and 28 (46.6%) cases, respectively. Co-over expression of those genes was observed in 17 (28.3%) cases and found to be statistically significant (p=0.001). The results also showed a strong association between c-MYC and grade of differentiation of the examined neoplasms (p=0.0217rpar;. CONCLUSION: Simultaneous c-MYC and h-TERT deregulation is a relatively frequent genetic event in colon adenocarcinoma. Because c-MYC overexpression is correlated with progressive disease - due to colon adenocarcinoma dedifferentiation - inhibition of its activity combined with h-TERT regulated expression is a new target for novel therapeutic regimens.
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Adenocarcinoma/enzimología , Biomarcadores de Tumor/análisis , Neoplasias del Colon/enzimología , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-myc/análisis , Telomerasa/análisis , Análisis de Matrices Tisulares/métodos , Adenocarcinoma/patología , Biopsia , Diferenciación Celular , Neoplasias del Colon/patología , Femenino , Humanos , Masculino , Adhesión en Parafina , Valor Predictivo de las Pruebas , Pronóstico , Regulación hacia ArribaRESUMEN
A compartmental, epidemiological, mathematical model was developed in order to analyze the transmission dynamics of Delta and Omicron variant, of SARS-CoV-2, in Greece. The model was parameterized twice during the 4th and 5th wave of the pandemic. The 4th wave refers to the period during which the Delta variant was dominant (approximately July to December of 2021) and the 5th wave to the period during which the Omicron variant was dominant (approximately January to May of 2022), in accordance with the official data from the National Public Health Organization (NPHO). Fitting methods were applied to evaluate important parameters in connection with the transmission of the variants, as well as the social behavior of population during these periods of interest. Mathematical models revealed higher numbers of contagiousness and cases of asymptomatic disease during the Omicron variant period, but a decreased rate of hospitalization compared to the Delta period. Also, parameters related to the behavior of the population in Greece were also assessed. More specifically, the use of protective masks and the abidance of social distancing measures. Simulations revealed that over 5,000 deaths could have been avoided, if mask usage and social distancing were 20% more efficient, during the short period of the Delta and Omicron outbreak. Furthermore, the spread of the variants was assessed using viral load data. The data were recorded from PCR tests at 417 Army Equity Fund Hospital (NIMTS), in Athens and the Ct values from 746 patients with COVID-19 were processed, to explain transmission phenomena and disease severity in patients. The period when the Delta variant prevailed in the country, the average Ct value was calculated as 25.19 (range: 12.32-39.29), whereas during the period when the Omicron variant prevailed, the average Ct value was calculated as 28 (range: 14.41-39.36). In conclusion, our experimental study showed that the higher viral load, which is related to the Delta variant, may interpret the severity of the disease. However, no correlation was confirmed regarding contagiousness phenomena. The results of the model, Ct analysis and official data from NPHO are consistent.
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Design and development of novel targeted therapeutic strategies is an innovation in handling patients with solid malignancies including breast, colon, lung, head & neck or even pancreatic and hepatocellular carcinoma. For a long time, immunohistocytochemistry (IHC/ICC) has been performed as a routine method in almost all labs for evaluating protein expression. Modern molecular approaches show that identification of specific structural and numerical imbalances regarding genes involved in signal transduction pathways provide important data to the oncologists. Alterations in molecules such as epidermal growth factor receptor (EGFR), HER2/neu, PTEN or Topoisomerase IIa affect the response rates to specific chemotherapeutic agents modifying also patients' prognostic rates. In situ hybridization (ISH) techniques based on fluorescence and chromogenic variants (FISH/CISH) or silver in situ hybridization (SISH) are applicable in both tissue and cell substrates. Concerning cytological specimens, FISH/CISH analysis appears to be a fast and very accurate method in estimating gene/chromosome ratios. In this paper, we sought to evaluate the usefulness of FISH/ CISH analysis in cytological specimens, describing also the advantages and disadvantages of these methods from the technical point of view.
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Aberraciones Cromosómicas , Hibridación in Situ/métodos , Neoplasias/genética , Animales , Humanos , Hibridación Fluorescente in Situ/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Transducción de Señal/fisiologíaRESUMEN
PURPOSE: HER2 depended signalling pathway is dereg-ulated in a subset of non small cell lung carcinoma (NSCLC). The tumor suppressor gene PTEN (10q21) regulates the HER2/PI3K/Akt signalling pathway. Our aim was to evaluate PTEN protein expression in NSCLC based on a quantitative analysis method correlating also the results with clinicopathological parameters. METHODS: Protein expression was determined by immunohistochemistry (IHC) in 61 paraffin-embedded cases of patients with NSCLC. Digital image analysis (staining intensity levels) was performed in the corresponding immunostained slides. RESULTS: Loss of PTEN expression was observed in 24 (39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%) cases. Multivariate analysis determined that PTEN overexpression was associated with lower risk to develop metastases (p=0.05). CONCLUSION: PTEN deregulation is a relatively frequent genetic event in NSCLC, associated with progressive metastatic process in those patients. Because of binding to the ErbB2 receptor, trastuzumab stabilizes and activates PTEN gene, and loss of its expression negatively affects the response rates in such patients.
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Carcinoma de Pulmón de Células no Pequeñas/química , Procesamiento de Imagen Asistido por Computador , Neoplasias Pulmonares/química , Fosfohidrolasa PTEN/análisis , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: p53 (gene location: 17p13.1) overexpression is a common event in pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignant neoplasm. Although specific mechanisms of p53 gene deregulation have been identified, correlation between p53 expression and chromosome 17 gross numerical imbalances (aneuploidy) are under investigation. METHODS: Using tissue microarray technology, 60 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored and re-embedded to the final recipient block. Immunohistochemistry (IHC) for p53 expression and chromogenic in situ hybridization (CISH) for chromosome 17 numerical alterations were performed. Digital image analysis was applied for p53 expression levels evaluation (Nuclear Labelling Index-NLIs). RESULTS: p53 overexpression was detected in 38/60 (63.3%), whereas chromosome 17 aneuploidy was observed in 21/60 (35%) cases, respectively. Polysomy was identified in 19 cases, whereas monosomy in 2 of them. p53 overall expression was strongly correlated to the stage of the examined tumors (p=0.02). Chromosome aneuploidy was not associated to tumors' stage and grade (p=0.42, p=0.71, respectively). Although overall chromosome 17 centromeric imbalances were not correlated with p53 overexpression (p=0.32), both cases with monosomy demonstrated high expression levels. CONCLUSION: p53 overexpression combined with chromosome 17 numerical imbalances characterizes a significant proportion of PDACs. Because commercially available antip53 antibodies detect mutant and also wild-type protein expression levels, chromosome 17 monosomy maybe is a gross genetic criterion for discriminating them due to point mutation that frequently affects the remaining allele.
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Aneuploidia , Biomarcadores de Tumor/análisis , Carcinoma Ductal Pancreático/diagnóstico , Cromosomas Humanos Par 17 , Neoplasias Pancreáticas/diagnóstico , Análisis de Matrices Tisulares , Proteína p53 Supresora de Tumor/análisis , Anciano , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Distribución de Chi-Cuadrado , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Pronóstico , Proteína p53 Supresora de Tumor/genética , Regulación hacia ArribaRESUMEN
PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in colon adenocarcinoma (CA) is a frequent event, whereas specific deregulation mechanisms in the corresponding signaling pathways remain under investigation. Our aim was to co-evaluate their expression correlated to the hypoxia inducible factor 1alpha (HIF-1a), which activates the transcription of VEGF gene. METHODS: 60 paraffin-embedded primary CAs were cored at 1.5 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-EGFR, -VEGF, and -HIF 1a monoclonal antibodies. Concerning EGFR, quantitative evaluation was based on a semi-automated analysis system. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes. RESULTS: Protein overexpression was observed in 13/60 (21.6%), 45/60 (75%) and 7/60 (11.6%) cases regarding EGFR, VEGF, and HIF 1a, respectively. CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant associations raised correlating stage to chromosome 7 (p=0.024), HIF 1a expression to tumor anatomical location (p=0.019) and also VEGF to HIF 1a expression (p=0.001), whereas EGFR expression was not associated to EGFR gene copies. CONCLUSION: According to our results, chromosome 7 instability is correlated to advanced disease, whereas a significant subset of CAs demonstrates an alternative, non- HIF 1a depended mechanism of VEGF overexpression. Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism.
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Adenocarcinoma/química , Neoplasias del Colon/química , Receptores ErbB/análisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Transducción de Señal , Análisis de Matrices Tisulares , Factor A de Crecimiento Endotelial Vascular/análisis , Adenocarcinoma/genética , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Aneuploidia , Inestabilidad Cromosómica , Cromosomas Humanos Par 7 , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Adhesión en Parafina , Transducción de Señal/genéticaRESUMEN
Paragangliomas of the larynx are rare neuroendocrine tumors with difficulties in diagnosis and management. A review of the literature was carried out, using Medline and other available databases. Electronic links and related books were also included. The most reliable diagnostic imaging procedures are MRI, CT scan, and octreotide scintigraphy. Complete surgical excision with the maximal possible preservation of the laryngeal function is the treatment of choice. Many different surgical techniques have been reported but open surgical procedures seem to provide better results with lower recurrence rates, although endoscopic approaches and laser surgery have also been used with variable results. The use of long-acting depot octreotide has been used for the relief of symptoms and stabilization of the disease, especially in inoperable lesions with positive initial octreotide scintigraphy imaging. Detailed preoperative assessment and treatment planning in individual basis are essential in the management of these tumors.
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Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirugía , Paraganglioma/diagnóstico , Paraganglioma/cirugía , Angiografía , Diagnóstico por Imagen , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Paraganglioma/tratamiento farmacológicoRESUMEN
Here is reported an extremely rare case of a large intraparotid facial nerve schwannoma in a 32-year-old female who presented with a parotid mass. There had been a long clinical course and sudden onset of facial weakness. Diagnostic evaluation and surgical management are discussed along with a brief review of the literature.
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Neoplasias de los Nervios Craneales/diagnóstico , Enfermedades del Nervio Facial/diagnóstico , Neurilemoma/diagnóstico , Glándula Parótida/inervación , Adulto , Biopsia con Aguja Fina , Parálisis Facial/diagnóstico , Femenino , Humanos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Topoisomerase II alpha (Topo IIa gene location 17q21) is a nucleic enzyme involved in the DNA replication, transcription and chromosome topological formation. Topo IIa inhibition strategies include specific chemotherapeutic agents such as anthracyclines. Our aim was to investigate potential protein alterations of the enzyme comparing them to ki 67 proliferation marker expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Using tissue microarray (TMA) technology, 50 specimens consisting of histologically confirmed PTCs (n=20), multi-nodular goiters (n=20) and also normal thyroid epithelia (n=10) were cored and re-embedded in the final paraffin block. Immunohistochemical analysis was performed using monoclonal anti-Topo IIa and anti-ki 67 (MIB-1) antibodies. Digital image analysis assay was also applied for the evaluation of the protein expression results (Nuclear Labeling Index-NLI). RESULTS: Topo IIa and ki 67 proteins were overexpressed in 4/20 (20%) and 14/20 (70%) cases, respectively. Concerning multi-nodular goiters, overexpression was observed in 2/20 and 4/20 specimens, respectively. Statistical association was assessed correlating ki 67 expression to pathology type, capsular invasion and also to vascular infiltration (p=0.001, p=0.008, and p=0.012, respectively). Topo IIa protein expression was strongly correlated only to capsular invasion (p=0.004). Overall expression of the examined markers demonstrated a medium concordance (kappa=0.27), but a strong association (p=0.001). CONCLUSION: Topo IIa and also ki 67 overexpression are correlated to an aggressive phenotype in PTC. Topo IIa overexpression maybe is a reliable marker for a rational application of targeted chemotherapeutic strategies in some subgroups of patients.
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Antígenos de Neoplasias/análisis , Carcinoma Papilar/patología , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Procesamiento de Imagen Asistido por Computador , Antígeno Ki-67/análisis , Neoplasias de la Tiroides/patología , Análisis de Matrices Tisulares/métodos , Carcinoma Papilar/química , Proliferación Celular , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Tiroides/químicaRESUMEN
PURPOSE: Deregulation of apoptotic pathways in cutaneous malignant melanoma appears to be correlated with chemoresistance and poor prognosis. Furthermore, telomerase (especially h-TERT) expression induces proliferation and also represents a potential target for vaccination regarding some types of malignancies. MATERIALS AND METHODS: Using tissue microarrays (TMA) technology, 25 paraffin-embedded tissue samples of histologically confirmed malignant melanomas were cored at a diameter of 2 mm and re-embedded into one recipient block (final TMA density 24/25-96%). Immunohistochemistry (IHC) was performed by the use of anti-bcl-2, anti-caspase 3, anti-caspase 8 and anti- h-TERT antibodies. Protein expression levels were evaluated using a computerized image analysis system (CIA). SPSS (chi square test and inter-rater kappa) was used for statistical analysis. RESULTS: Strong protein expression was observed in 1/24 (4.1%), 1/24 (4.1%), 2/24 (8.2%), and 4/24 (16.4%) cases regarding h-TERT, caspase 3, caspase 8 and bcl-2, respectively. Moderate was observed in 7/24 (29.1%), 8/24 (32.2%), 5/24 (20.2%), and 8/24(32.2%) cases, whereas reduced or absent expression demonstrated 16/24 (65%), 15/24 (60.2%), 17/24 (68.5%), and 12/24 (50 %) cases. Statistical significance was assessed correlating age to caspase 3 (p=0.05), Breslow's thickness to telomerase (p=0.013) and to bcl-2 (p=0.053), Clark's level to telomerase (p=0.008) and to bcl-2 (p=0.022), and finally ulceration to telomerase expression (p=0.007). CONCLUSION: bcl-2 and telomerase expression are correlated to critical parameters of malignant melanoma, affecting its biological behavior. Furthermore, downregulation of proteins such as caspases 3/8, which normally induce apoptosis, is perhaps associated with resistance of the applied chemotherapeutic strategies in this type of malignancy.
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Biomarcadores de Tumor/metabolismo , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Biomarcadores de Tumor/análisis , Caspasa 3/análisis , Caspasa 3/metabolismo , Caspasa 8/análisis , Caspasa 8/metabolismo , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Masculino , Melanoma/patología , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias Cutáneas/patología , Telomerasa/análisis , Telomerasa/metabolismo , Análisis de Matrices TisularesRESUMEN
PURPOSE: Deregulation of cell cycle control molecules, such as cyclins and their inhibitors, is a crucial event in the carcinogenetic process. Our aim was to identify potential correlations between p16 and cyclin D1 expression in pancreatic ductal adenocarcinoma (PDAC) that affect the biological behavior of this neoplasm. MATERIALS AND METHODS: Using tissue microarray (TMA) technology, 50 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored twice and re-embedded to the final recipient block. Immunohistochemistry (IHC) was performed using monoclonal anti-p16 and anti-cyclin D1 antibodies. Protein expression levels were determined by performing computerized image analysis (CIA; estimation of Nuclear Labeling Index-NLI). SPSS (chi square test and interrater Cohen's kappa) was used for statistical analysis. RESULTS: Cyclin D1 overexpression was observed in 24/50 (48%) of the examined carcinomas, whereas p16 loss or reduced expression was detected in 40/50 (80%) cases. Statistical significance was noted when correlating grade to cyclin D1 (p=0.038), stage to p16 (p=0.012) and also to cyclin D1 (p=0.011). Interestingly, combined protein alterations (p16 loss and cyclin D1 overexpression) were observed in 23/50 (46%) cases associated with advanced stage (p=0.019). Overall combined expression of the two molecules demonstrated a significantly low value (kappa=0.012; 95% confidence interval-CI: 0.010-0.014). CONCLUSION: A significant proportion of PDACs is characterized by simultaneous protein alterations regarding p16 and cyclin D1 genes. This mechanism of genetic deregulation in cell cycle potentially explains in part the aggressive phenotype of this neoplasm.
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Carcinoma Ductal Pancreático/genética , Ciclina D1/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Regulación Neoplásica de la Expresión Génica , Genes bcl-1 , Genes p16 , Neoplasias Pancreáticas/genética , Anciano , Ciclina D1/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis de Matrices TisularesRESUMEN
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm. Many different chromosomal alterations have been identified including structural or numerical changes. In this study we performed a molecular analysis of chromosomes 7,9, and 17 based on tissue microarrays (TMA). MATERIALS AND METHODS: Using TMA technology, 50 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored twice and re-embedded to the final recipient block. Chromogenic in situ hybridization (CISH) was performed using centromeric probes of the corresponding chromosomes. SPSS(chi square test and interrater kappa) was performed for statistical analysis. RESULTS: Chromosome 17 analysis detected aneuploidy in 19 (38%) cases. Similarly, aneuploidy regarding chromosome 9 was identified in 9 (18%) cases, whereas 14 (28%) cases were aneuploid, concerning chromosome 7. Statistical significance was assessed, correlating chromosome 7 with grade and stage (p=0.016 and p=0.027, respectively) and chromosome 9 to grade (p=0.023). Similarly, analyzing normal-appearing ductal epithelia adjacent to cancer cell populations, 2 cases were found with alterations regarding chromosome 9 and 17. CONCLUSION: Molecular analysis for chromosomes 7, 9 and 17 in PDAC confirmed that there is a variety of numerical alterations, and some of them represent very early genetic events in the progression of carcinogenetic process. Performance of CISH, also, provides an easy, accurate approach for their detection, even in a small tissue sample, such as TMA cylindrical cores.
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Carcinoma Ductal Pancreático/genética , Aberraciones Cromosómicas , Neoplasias Pancreáticas/genética , Anciano , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 7/genética , Cromosomas Humanos Par 9/genética , Femenino , Humanos , Hibridación in Situ/métodos , Masculino , Persona de Mediana Edad , Análisis de Matrices Tisulares/métodosRESUMEN
PURPOSE: Telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. It consists of two main components which include a RNA subunit (h-TERC) and a catalytic protein subunit (h-TERT). Similarly, amplification or deletion correlating with overexpression of c-myc is a common event in various neoplasias, including non-small cell lung carcinoma (NSCLC). Because c-myc activates telomerase by inducing expression of its catalytic subunit, our aim was to correlate the expression of these two proteins with the biological behavior in NSCLC. MATERIALS AND METHODS: Using tissue microarrays technology (TMA) we evaluated by computerized image analysis (CIA) the results of h-TERT and c-myc immuno-histochemistry (IHC) in 40 NSCLCs, which were cored and re-embedded into one TMA block. RESULTS: Co-overexpression (moderate or high levels of NLI: Nuclear Labeling Index) of h-TERT and c-myc was observed in the majority of cases and found to be statistically significant (p=0.001). The results showed also strong association between c-myc and h-TERT overexpression correlating with stage (p=0.001 for both of them), but not with grade (p=0.206 and p=0.313, respectively). CONCLUSION: Our combined study showed that there is a strong correlation between the activation and expression of these two genes and maybe this co-deregulation could be used as a prognostic factor for the evaluation of biological behavior in NSCLCs.
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Impetigo is a contagious superficial pyogenic infection of the skin caused by Staphylococcus aureus and/or by group A Streptococcus. Two main clinical forms are recognized: bullous impetigo and non-bullous impetigo. We present an unusual case of pustular impetigo in a 35-year-old man. The pustules were localized symmetrically in the groin and the patient was successfully treated with clarithromycin. In bullous impetigo, exfoliative toxins produced by Staphylococcus aureus are accepted as the basis for the bulla formation just below the stratum granulosum. Although clarithromycin is considered to be a second-choice therapy for bullous impetigo, it was highly effective in our case.
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Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Impétigo/tratamiento farmacológico , Adulto , Humanos , Impétigo/patología , MasculinoRESUMEN
Dermoid cyst of the spermatic cord is a very rare clinical entity with only a few cases reported in the literature so far. We herein describe an extremely rare case of a large dermoid cyst of the spermatic cord measuring 8.5 x 5 x 5 cm in a young patient who presented with clinical manifestations of an incarcerated inguinal hernia. After the cyst excision, a diffuse direct hernia became apparent and a Lichtenstein polypropylene mesh repair was performed. Direct hernia was likely the result of chronic pressure on the inguinal floor maintained by the large cyst. We conclude that although very rare, dermoid cyst of the spermatic cord should be considered as a part of the differential diagnosis in patients presenting with an irreducible inguinal mass of a long course.
Asunto(s)
Quiste Dermoide/diagnóstico , Neoplasias de los Genitales Masculinos/diagnóstico , Hernia Inguinal/diagnóstico , Cordón Espermático , Humanos , Masculino , Adulto JovenRESUMEN
Idiopathic retroperitoneal fibrosis (IRF) entirely confined to the pelvic cavity is an extremely rare clinical entity. Herein, is described the case of a 36- year old male who presented with clinical and imaging manifestations of a large pelvic tumor. Exploratory laparotomy revealed a large mass in the right pelvis originating from the retroperitoneal space, displacing the right iliac vessels, the right ureter and the urinary bladder completely to the left. A laborious resection of the mass measuring 14 x 10cm was performed. Histopathological examination and detailed immunohistochemistry analysis were suggestive of idiopathic retroperitoneal fibrosis with no evidence of malignancy. This is a very rare case regarding localization and clinical presentation of idiopathic retroperitoneal fibrosis. We conclude that IRF should be included in the differential diagnosis of patients presenting with a pelvic mass even if there is no involvement of the typical para aortic area.
Asunto(s)
Neoplasias Pélvicas/diagnóstico , Pelvis/patología , Fibrosis Retroperitoneal/diagnóstico , Adulto , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Arteria Ilíaca/patología , Vena Ilíaca/patología , Masculino , Tomografía Computarizada por Rayos X , Uréter/patología , Vejiga Urinaria/patologíaRESUMEN
AIMS: To investigate the potential role of caspase-3 and caspase-8 protein expression in the biological behaviour of tongue squamous cell carcinoma. MATERIALS AND METHODS: We conducted immunohistochemical analyses of 87 specimens of primary tongue squamous cell carcinoma, using monoclonal anti-caspase-3 and anti-caspase-8 antibodies. A digital image analysis assay was also performed in order to evaluate the results. RESULTS: Reduced expression of caspase-8 and -3 proteins was observed in 30/87 (34.5 per cent) and 79/87 (90.5 per cent) cases, respectively. Cox regression analysis showed no prognostic significance for the association between overall protein expression of either marker and survival probability (p = 0.174 for caspase-3; p = 0.608 for caspase-8). Interestingly, the size of the examined tumours was strongly correlated with survival status (p = 0.024). CONCLUSIONS: Simultaneous deregulation of caspase-8 and -3 is a frequent event in tongue squamous cell carcinoma. Activation of caspase-3, which is predominantly down-regulated, may be a crucial process for induction of apoptosis and response to therapeutic strategies.