RESUMEN
BACKGROUND: Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of glioblastoma (GBM). The poor survival of GBM was mainly associated with the presence of glioma stem cells (GSC) and the markedly inflammatory microenvironment. To further explore the involvement of COX-2 in glioma biology, the effects of NS398, a selective COX-2 inhibitor, were evaluated on GSC derived from COX-2 expressing GBM cell lines, i.e., U87MG and T98G, in terms of neurospheres' growth, autophagy, and extracellular vesicle (EV) release. METHODS: Neurospheres' growth and morphology were evaluated by optical and scanning electron microscopy. Autophagy was measured by staining acidic vesicular organelles. Extracellular vesicles (EV), released from neurospheres, were analyzed by transmission electron microscopy. The autophagic proteins Beclin-1 and LC3B, as well as the EV markers CD63 and CD81, were analyzed by western blotting. The scratch assay test was used to evaluate the NS398 influence on GBM cell migration. RESULTS: Both cell lines were strongly influenced by NS398 exposure, as showed by morphological changes, reduced growth rate, and appearance of autophagy. Furthermore, the inhibitor led to a functional change of EV released by neurospheres. Indeed, EV secreted by NS398-treated GSC, but not those from control cells, were able to significantly inhibit adherent U87MG and T98G cell migration and induced autophagy in recipient cells, thus leading to effects quite similar to those directly caused by NS398 in the same cells. CONCLUSION: Despite the intrinsic diversity and individual genetic features of U87MG and T98G, comparable effects were exerted by the COX-2 inhibitor NS398 on both GBM cell lines. Overall, our findings support the crucial role of the inflammatory-associated COX-2/PGE2 system in glioma and glioma stem cell biology.
RESUMEN
Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p < 0.001) and NRASQ61R (k = 0.87; p < 0.001). These findings demonstrate a relevant intra-patient heterogeneity between primary and metastatic lesions that is independent of clinical variables and methodological approach.
Asunto(s)
Biomarcadores de Tumor/genética , GTP Fosfohidrolasas/genética , Heterogeneidad Genética , Melanoma/genética , Proteínas de la Membrana/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Melanoma/secundario , Persona de Mediana Edad , Fenotipo , Proteínas Proto-Oncogénicas c-kit/genética , Neoplasias Cutáneas/patologíaRESUMEN
Nowadays, fat tissue transplantation is widely used in regenerative and reconstructive surgery. However, a shared method of lipoaspirate handling for ensuring a good quality fat transplant has not yet been established. The study was to identify a method to recover from the lipoaspirate samples the highest number of human viable adipose tissue-derived stem cells (hADSCs) included in stromal vascular fraction (SVF) cells and of adipocytes suitable for transplantation, avoiding an extreme handling. We compared the lipoaspirate spontaneous stratification (10-20-30 min) with the centrifugation technique at different speeds (90-400-1500 × g). After each procedure, lipoaspirate was separated into top oily lipid layer, liquid fraction, "middle layer", and bottom layer. We assessed the number of both adipocytes in the middle layer and SVF cells in all layers. The histology of middle layer and the surface phenotype of SVF cells by stemness markers (CD105+, CD90+, CD45-) was analyzed as well. The results showed a normal architecture in all conditions except for samples centrifuged at 1500 × g. In both methods, the flow cytometry analysis showed that greater number of ADSCs was in middle layer; in the fluid portion and in bottom layer was not revealed significant expression levels of stemness markers. Our findings indicate that spontaneous stratification at 20 min and centrifugation at 400 × g are efficient approaches to obtain highly viable ADSCs cells and adipocytes, ensuring a good thickness of lipoaspirate for autologous fat transfer. Since an important aspect of surgery practice consists of gain time, the 400 × g centrifugation could be the recommended method when the necessary instrumentation is available.
Asunto(s)
Adipocitos/citología , Tejido Adiposo/trasplante , Lipectomía/métodos , Manejo de Especímenes/métodos , Células Madre/citología , Adulto , Linaje de la Célula , Femenino , Citometría de Flujo , Humanos , Técnicas In Vitro , Persona de Mediana EdadRESUMEN
Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2'-deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.
Asunto(s)
Endometriosis/metabolismo , Quistes Ováricos/metabolismo , Ovario/metabolismo , Estrés Oxidativo/fisiología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Biomarcadores/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Endometriosis/patología , Femenino , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Quistes Ováricos/patología , Ovario/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To understand if repeated cycles (2-4 rounds) of gonadotropin stimulation could affect intracellular localization/content of proteins controlling cell cycle progression in mouse fallopian tubes (FT) and ovaries. METHODS: FT and ovaries of estrous mice (control) and of stimulated mice were analyzed to detect Oct-3/4, Sox-2, p53, ß-catenin, pAKT and cyclin D1 localization/content. Spindles and chromosome alignment were analyzed in ovulated oocytes. RESULTS: After round 4, FT and ovaries of control and stimulated groups showed no differences in Oct-3/4, Sox-2 and ß-catenin localization nor in Oct-3/4, Sox-2, p53, ß-catenin and pAKT contents. Cyclin D1 level increased significantly in FT of treated mice. Oocytes number decreased meanwhile frequency of abnormal meiotic spindles increased with treatments. CONCLUSIONS: Repetitive stimulations affected oocyte spindle morphology but did not induce changes in a set of proteins involved in cell cycle progression, usually altered in ovarian cancer. The significant increase of cyclin D1 in the FT requires further investigation.
Asunto(s)
Puntos de Control del Ciclo Celular/genética , Trompas Uterinas/metabolismo , Ovario/metabolismo , Inducción de la Ovulación , Animales , Trompas Uterinas/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Gonadotropinas/administración & dosificación , Ratones , Ovario/efectos de los fármacosRESUMEN
Emerging evidence indicates that interactions between chemokine receptors and their ligands may have a critical role in several steps of tumor development, including tumor growth, progression, and metastasis. In this report, we retrospectively evaluated CXCR4 expression in a consecutive series of 200 papillary thyroid carcinomas. We investigated the relationship between the clinicopathological features of the tumors and mutations in the BRAF gene to verify whether overexpression of CXCR4 is linked to more aggressive behavior in thyroid tumors. CXCR4 protein expression was evaluated by immunohistochemical staining. A final staining score was calculated by adding the score representing the percentage of positive cells to the intensity score. The CXCR4 expression of each papillary thyroid carcinoma sample was normalized by calculating the z score for each final staining score. Univariate analysis was used to correlate CXCR4 expression with the papillary thyroid carcinoma variant, the degree of neoplastic infiltration, the American Joint Commission on Cancer stage, the presence of lymphocytic thyroiditis and the mutation status of the BRAF gene. Multiple regression analysis confirmed a strong association between CXCR4, BRAF mutation and the degree of neoplastic infiltration. These data clearly indicate that the chemokine receptor expression induced by oncogenic activation could be the major determinant of the local aggressiveness of neoplastic cells. In conclusion, our data indicate that CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland.
Asunto(s)
Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Receptores CXCR4/análisis , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma , Carcinoma Papilar , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Italia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Oportunidad Relativa , Pronóstico , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores CXCR4/genética , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Adulto JovenRESUMEN
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a recently identified death factor that acts as a potent apoptosis inducer in ameloblastomas. MATERIALS AND METHODS: The expression of TRAIL and its receptors (TRAIL-R), and the location of apoptotic cells were evaluated in 15 cases of ameloblastoma using immunohistochemistry and an in situ DNA nick-end labeling method. The proliferative activity of ameloblastomas was analyzed by determining the Ki-67 labeling index. RESULTS: TRAIL and TRAIL-R were diffusely expressed in ameloblastomas, without clear correlation with the location of apoptotic cells. Apoptosis and proliferation were opposite in the peripheral and central components of the ameloblastomas. In some ameloblastoma variants, apoptosis and proliferation seemed to modify in the same direction. CONCLUSION: TRAIL and its receptors might be involved in neoplastic transformation of odontogenic epithelium and might suggest some intrinsic regulation of neoplastic cell proliferation and death in ameloblastomas, thus explaining their slow growth and inability to metastasize.
Asunto(s)
Ameloblastoma/patología , Apoptosis , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Miembro 10c de Receptores del Factor de Necrosis Tumoral/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ameloblastoma/metabolismo , Proliferación Celular , Femenino , Humanos , Técnicas para Inmunoenzimas , Etiquetado Corte-Fin in Situ , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In literature there are few reports about multiple CGCG. But this is the first report of bilateral CGCG of the mandibular angles in three females from the same family.This report describes three cases of females from the same family - a mother and two young daughters - with bilateral CGCG in their jaw angles. All the lesions were surgically removed and the histopathologic diagnosis was always identical: giant cell central granulomas, with patterns that were absolutely superimposable between them and with that of the mother.The hypothesis is that this presentation of CGCG may be defined as hereditary bilateral CGCG of the mandibular angles (or also, cherubism-like lesions).
Asunto(s)
Querubismo/genética , Predisposición Genética a la Enfermedad , Granuloma de Células Gigantes/genética , Enfermedades Mandibulares/genética , Monitoreo Fisiológico/métodos , Biopsia con Aguja , Niño , Femenino , Granuloma de Células Gigantes/diagnóstico por imagen , Granuloma de Células Gigantes/patología , Granuloma de Células Gigantes/cirugía , Humanos , Inmunohistoquímica , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/patología , Enfermedades Mandibulares/cirugía , Persona de Mediana Edad , Procedimientos Quirúrgicos Orales/métodos , Linaje , Pronóstico , Radiografía Panorámica/métodos , Enfermedades Raras , Medición de RiesgoRESUMEN
Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600E detection (κ = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test.
Asunto(s)
GTP Fosfohidrolasas/genética , Predisposición Genética a la Enfermedad , Melanoma/genética , Proteínas de la Membrana/genética , Mutación/genética , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas B-raf/genética , Receptor de Melanocortina Tipo 1/genética , Telomerasa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Heterogeneidad Genética , Mutación de Línea Germinal/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Dirofilaria repens , Dirofilariasis , Orquiectomía , Enfermedades Testiculares , Animales , Dirofilariasis/parasitología , Dirofilariasis/patología , Dirofilariasis/cirugía , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Testiculares/parasitología , Enfermedades Testiculares/patología , Enfermedades Testiculares/cirugía , Testículo/parasitología , Testículo/patología , Testículo/cirugía , Zoonosis/parasitologíaRESUMEN
BACKGROUND: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). METHODS: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. RESULTS: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7-59.4). CONCLUSIONS: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.
RESUMEN
The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is being increasingly investigated. HtrA1 overexpression inhibits cell growth and proliferation by influencing apoptosis, invasiveness and migration of tumour cells. In the present study, HtrA1 expression was analysed in 228 colon tissue samples from patients with CRC, adenoma with high-grade dysplasia (AHD), adenoma with low-grade dysplasia (ALD), ulcerative colitis of >10 year duration (UCL), ulcerative colitis of <5 year duration (UCS) and colonic diverticulitis (D), and was compared with its expression in normal colon tissues (NCTs) collected 5 cm from the CRC lesion and in healthy colon mucosa (HC), to establish whether HtrA1 can serve as a biomarker for these conditions. All tissue specimens came from Italian Caucasian subjects. The main finding of the present study was that HtrA1 expression was significantly reduced in CRC and UCL tissues compared with that observed in both NCT and HC samples and with tissues from the other patients. In particular, a similar HtrA1 expression was detected in the stromal compartment of UCL and CRC samples. In contrast, the HtrA1 level was significantly lower (p=0.0008) in UCL compared with UCS tissues, suggesting an inverse relationship between HtrA1 expression and ulcerative colitis duration. HtrA1 immunostaining in the stromal compartment of AHD and ALD tissues showed no differences compared with the HC tissues. No data are available on the immunohistochemical localization of HtrA1 in CRC or IBD. The present findings suggest that HtrA1 could serve as a marker to identify UCL patients at high risk of developing CRC.
Asunto(s)
Adenoma/patología , Colitis Ulcerosa/patología , Neoplasias Colorrectales/patología , Diverticulitis del Colon/patología , Serina Peptidasa A1 que Requiere Temperaturas Altas/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia , Colitis Ulcerosa/complicaciones , Colon/patología , Neoplasias Colorrectales/etiología , Diverticulitis del Colon/complicaciones , Femenino , Humanos , Inmunohistoquímica , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Our previous study on 75 cases of advanced oral squamous cell carcinomas (SCC) treated by neoadjuvant chemotherapy, radical surgery, and radiotherapy showed that overexpression of p53 of more than 50% indicated a strong probability of genetic mutation, and tumours that are characterised by this p53 pattern respond poorly to treatment and have a poor prognosis (p= 0.0001). We have studied the same cohort of patients retrospectively to investigate the incidence of human papillomavirus-16 (HPV16) infection, the relation to the overexpression or mutation of the p53 gene, and the association with overall survival. There were 57 men and 18 women, mean age 67 (range 57-72) years. HPV16 infectivity was found in 66 patients (88%) - 49/57 men (86%) and 17/18 women (94%). There was no significant difference between the sexes (p=0.32). The cumulative survival of the entire group after a follow-up of 38 months was 26% (SE 6.4). The log rank test indicated that the combination of HPV-16 infectivity and p53mutation was significantly related to prognosis (p=0.000). On the other hand HPV16 infectivity alone was not significantly related to prognosis (p=0.78) The incidence of HPV-16 infection decreased with increasing immune p53 expression (p=0.005), whereas that of the HPV16+p53mutation combination increased with increasing immune p53 expression (p=0.000). The results show the importance of the investigation of HPV and p53 expression to define prognosis in oral SCC.
Asunto(s)
Neoplasias de la Boca , Infecciones por Papillomavirus , Proteína p53 Supresora de Tumor/análisis , Anciano , Carcinoma de Células Escamosas , Femenino , Papillomavirus Humano 16 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Oral squamous cell carcinoma (OSCC) is often associated with a poor prognosis. The purpose of the present study was to investigate survival and the risk of mortality in OSCC with regard to stage, tumor site and p53 expression. A retrospective study was performed on 150 non-consecutive cases of OSCC that were observed between January 1992 and January 2012, and were selected from a total of 580 patients according to the criteria of the homogeneity of histopathological grading (G2). The medical records were reviewed for 48 cases with disease at stage I [37 males, age 64.7±5.7 years (mean age±standard deviation); 11 females, age 70.0±3.37 years]; 27 cases with stage II (15 males, age 64.5±5.6 years; 12 females, age 69.2±3.9 years); 58 cases with stage IVa (42 males, age 66.9±5.3 years; 16 females, age 64.2±6.5 years); and 17 cases with stage IVb (16 males, age 65.7±5.4 years; 1 female, age 69 years). Monoclonal p53 antibody (clone DO-7) was used to perform the p53 immunohistochemical study. A significant association was found between the site of the tumor and p53 overexpression (P<0.0001). Stage I-II cases showed a higher cumulative probability of a 24-month survival time than stage IVa-IVb cases (P<0.0001). Cheek, floor and soft palate tumors showed a worse prognosis (P<0.0001) and tumors with p53 overexpression >50% showed a poor survival rate (P<0.0001) compared with tumors of the attached gingiva, tongue and retromolar trigone. The findings allowed the quantification of the risk mortality from OSSC with regard to stage, tumor site and the p53 expression pattern of the tumor. Data supported the absolute indications for wide surgical margins (radical surgery) in cases of T1-T2 N0 tumors of the tongue, floor, retromolar trigone and attached gingiva when p53 overexpression is >50% in association with a higher risk of mortality compared with when p53 overexpression is <50%.
RESUMEN
Angiogenesis is a central process in the growth of solid tumors. The purpose of our study was to analyze the angiogenic pattern in squamous and basal cell carcinomas and to point out differences in microvessel density that could explain their different biological behaviour. Thirty-nine skin tumors (26 basal and 13 squamous cell carcinomas) were analyzed. In all samples, the microvessels density (MVD) and the levels of vascular endothelial growth factor mRNA (VEGFmRNA) were analyzed, together with the inter-relationship between these two variables. Using the median value of the entire series (33 vessels per 2.22 mm2), tumors with low and high MVD were identified. The majority of cancers with high vascularization belonged to the squamous histotype (12 of 39), while 19 of the 26 basal cell carcinomas showed a lower number of microvessels than the median value (p = 0.0001). The median value of VEGFcDNA quantitation allowed us to distinguish tumors with high VEGF expression (> 470 molecules cDNA) from those with low (< or = 470 molecules) VEGF expression: 20 of the 26 basal cell carcinomas showed low VEGF expression, while 11 of the 13 squamous cell carcinomas showed high VEGFcDNA levels (p = 0.0003). Moreover, a significant association between a high microvessel density and high VEGFmRNA levels (p = 0.006) was found. Furthermore, when studying VEGF expression by immunohistochemistry, we obtained similar results and noted a correlation with VEGFmRNA expression (p < 0.0001). The association between high vascularization, high VEGF levels, and squamous cell histotype suggests the possible role of neoangiogenesis in determining the more aggressive biological behaviour of this type of cancer.
Asunto(s)
Carcinoma Basocelular/irrigación sanguínea , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/metabolismo , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Microcirculación , Persona de Mediana Edad , Neovascularización Patológica , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
In the present study, the telomerase activity and the putative alterations of genes involved in cell-cycle control (p53, Fas and pRb) were investigated in a radiation-induced meningioma with multiple recurrences and pleural-pulmonary metastases (the patient, a 34-year-old male, had a history of carcinoma of the tongue of testicular lymphocytic lymphoma). Expression of VEGF and vasculature pattern were also studied. Expression of VEGF, pRb and p53 were evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded samples of the tumor. VEGFmRNA was determined by competitive PCR. Fas, FasL and hTERT were evaluated by RT-PCR. Telomerase activity was examined by the TRAP assay. An intense vascularization was observed, supported by high expression of VEGFmRNA (isoforms 121 and 165). pRb and p53 were overexpressed. Fas was undetectable with PCR, whereas FasL was positive. Furthermore, the lesion showed an elevated telomerase activity (TPG, 22), according to the high expression of hTERT. These findings emphasized that even among generally benign neoplasms, such as meningiomas, some highly malignant tumors may develop, as in our case, in which several mechanisms were activated in the cancer progression to guarantee the immortalization of cellular clones (angiogenic phenomenon, activation of telomerase and of anti-apoptotic mechanisms) and the blood spread. Thus, the data illustrate the importance of searching for genetic aberrations (which are a hallmark of malignancy) in meningiomas, as predictive and reliable factors of the possibility to recur and to metastasize.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/secundario , Neoplasias Meníngeas/química , Neoplasias Meníngeas/patología , Meningioma/química , Meningioma/secundario , Neoplasias Pleurales/secundario , Adulto , Biomarcadores de Tumor/genética , Proteínas de Unión al ADN , Proteína Ligando Fas , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Glicoproteínas de Membrana/análisis , Neoplasias Meníngeas/etiología , Meningioma/etiología , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , ARN Mensajero/análisis , Radioterapia/efectos adversos , Proteína de Retinoblastoma/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Telomerasa/análisis , Neoplasias de la Lengua/radioterapia , Proteína p53 Supresora de Tumor/análisis , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/análisis , Receptor fas/análisisRESUMEN
Standardized histopathology reporting represents the most effective approach to the diagnosis of malignant tumors. The use of checklists is considered the best single practice in ensuring the completeness of daily reporting and enables the pathologist to provide crucial information, affecting therapeutic decisions. Despite the huge amount of available protocols, a great variability is still found in prostate cancer reports, particularly on the expense of core needle biopsies. The aim of the present study is to evaluate the effectiveness of an original reporting system, based on the most recent contributions about prognostic factors of prostate carcinoma. The protocol is designed to provide guidance in formulating histopathology reports, by using three different checklists, each devoted to a single kind of specimen (needle biopsy, TURP/simple prostatectomy, radical prostatectomy). Before introducing this protocol in daily practice we tested its effectiveness on a series of cases undergone conventional, descriptive reporting. The omissions in conventional reports and the differences between the two systems enabled us to confirm the value of our method. Despite an additional workload for the pathologist, this standardized reporting system allows the urologist to easily obtain significant prognostic data, select the patients to be treated and predict the clinical outcome after surgery.
Asunto(s)
Biopsia con Aguja , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/patología , Resección Transuretral de la Próstata , Anciano , Biopsia con Aguja/métodos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugíaRESUMEN
BACKGROUND: The forkhead transcription factor FoxP3 plays an important role in regulatory T cell (Treg) functions. Tregs are critical in maintaining immunologic tolerance. It has been shown that vaccination against FoxP3-expressing cells is associated with enhancement of tumor immunity. Tregs appear to be increased in blood and in the tumor microenvironment of patients with different cancer types. Tumor cells themselves can express FoxP3. The present study investigates the possible role of FoxP3 expression in a series of human papillary thyroid cancers with a mean follow-up time of 15 years. METHODS: One hundred five cases of papillary thyroid carcinoma (PTC) were investigated, and FoxP3 expression was evaluated in both tumor cells and tumor-associated infiltrates. For all patients, clinical/pathologic features were considered and the results analyzed by statistical tests. RESULTS: Of the 105 PTC cases, 45 (43%) scored FoxP3-positive and 60 (57%) were negative. FoxP3 staining was localized predominantly in the cytoplasm of tumor cells. In some cases, both nuclear and cytoplasmic staining was seen in infiltrating cells. FoxP3 expression in tumor cells was correlated with the presence of extrathyroid invasion (p=0.04) and distant metastasis (p=0.04), but not with overall survival. Interestingly, FoxP3 expression in neoplastic cells was significantly associated with a resistance phenotype to radioiodine treatment (p=0.041). CONCLUSIONS: The data show an association of FoxP3 expression with features of PTC that seem to have a specific impact on radioiodine sensitivity.
Asunto(s)
Carcinoma Papilar/patología , Carcinoma/patología , Factores de Transcripción Forkhead/biosíntesis , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/patología , Adulto , Biomarcadores de Tumor , Carcinoma/inmunología , Carcinoma Papilar/inmunología , Resistencia a Antineoplásicos , Femenino , Factores de Transcripción Forkhead/inmunología , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Linfocitos T Reguladores/inmunología , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/inmunologíaRESUMEN
We have analysed concentrations of the p53 protein in advanced oral carcinomas immunohistochemically and genetically to detect the percentage of overexpression of this antioncogene that indicates a high probability of mutation. This would point to it being a useful prognostic factor, if we consider the importance of the relation between genetic alterations of p53 and poor overall survival. Seventy-five non-consecutive patients with oral squamous cell carcinoma and metastatic nodes were enrolled if there was homogeneity in histopathological grading (G2) of their tumours, and they were treated according to a multidisciplinary treatment plan. Monoclonal antibodies, extraction of DNA, and amplification of the polymerase chain reaction (PCR) were used for the immunohistochemical and genetic analyses. There was a significant inverse correlation between p53 overexpression and response to chemotherapy and a stronger association between high P53 overexpression (%) and a genetic mutation of p53 (p=0.0001). More than 50% overexpression indicated a strong probability of genetic mutation. There was no association between response to chemotherapy and age-groups or TNM classification (p=0.2), but there was a significant one between sex and site of tumour (p<0.001). Three prognostic factors were significantly related to prognosis: site of tumour (p=0.01), response to chemotherapy (p=0.002), and immuno p53 (p=0.0001). A tumour that is characterised by p53 overexpression of more than 50% indicates a poor prognosis.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/cirugía , Proteína p53 Supresora de Tumor/análisis , Factores de Edad , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/secundario , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Mutación/genética , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Factores Sexuales , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
The diagnosis of solitary fibrous tumor (SFT) is usually straightforward if the typical morphologic features, including a wide variety of growth patterns, are identified. We report the clinical, radiologic, and pathologic findings of a rare case of intraoral SFT which exhibited a predominant leiomyomatous-like appearance, closely reminiscent of a leiomyoma, at both incisional and excisional biopsy. Histologically, the tumor was composed predominantly of intersecting fascicles of eosinophilic spindle-shaped cells, variably set in a fibrous stroma. A focal hemangiopericytoma-like growth pattern with alternating hypercellular and hypocellular areas, as well as the deposition of dense keloid-type collagen, raising the suspicion of SFT, could be identified only after a careful examination of the whole tumor. Immunohistochemistry was helpful in confirming the diagnosis of SFT, revealing a diffuse staining of neoplastic cells for vimentin, CD34, bcl-2 protein, and, focally, CD99. Myogenic markers (alpha-smooth muscle actin, desmin, h-caldesmon) were not expressed. The pathologist should be aware of this variant of intraoral leiomyomatous-like SFT to avoid a misdiagnosis of leiomyoma. The distinction of SFT from leiomyoma in the oral cavity is important to assure both correct treatment and prognostic information.