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BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.
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Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Trasplante de Órganos , Infecciones por Polyomavirus , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Carcinoma de Células de Merkel/patología , Humanos , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Serina-Treonina Quinasas TOR , Infecciones Tumorales por Virus/complicacionesRESUMEN
INTRODUCTION & OBJECTIVES: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program. MATERIALS & METHODS: Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined. RESULTS: SelectMDx showed statistically significant differences related to PPFS (HR 1.035, 95%CI: 1.012-1.057) (pâ¯=â¯0.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805). CONCLUSIONS: In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.
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Neoplasias de la Próstata , Espera Vigilante , Antígenos de Neoplasias , Biopsia , Humanos , Masculino , Estudios Prospectivos , Neoplasias de la Próstata/diagnósticoRESUMEN
Cancers develop by sustained growth, migration and invasion properties of tumour cells, supported by complex interactions with stromal cells within the tumour micro-environment. This review is focused on the latest discoveries regarding the highlighted role of angiogenesis and tumour micro-environment in ovarian cancer. This cancer milieu encompasses non-cancerous cells present in the tumour or nearby, including vessel-forming cells, fibroblasts and immune cells amongst others that work in a cooperative way with cancer cells, impacting tumour behaviour. Angiogenesis, migration and invasion, and more recently immune evasion, are cancer hallmarks clearly dependent on these supporting cells. Moreover, these stromal cells are more genetically stable than tumour cells and thus represent an attractive therapeutic target. A better understanding of the stromal cells function, and their complex interplay with cancer cells, will open additional areas to target, as the tumour-host interface.
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The exopolymer (EPSp) produced by the strain B. licheniformis IDN-EC was isolated and characterized using different techniques (MALDI-TOF, NMR, ATR-FTIR, TGA, DSC, SEM). The results showed that the low molecular weight EPSp contained a long polyglutamic acid and an extracellular teichoic acid polysaccharide. The latter was composed of poly(glycerol phosphate) and was substituted at the 2-position of the glycerol residues with a αGal and αGlcNH2. The αGal O-6 position was also found to be substituted by a phosphate group. The antiviral capability of this EPSp was also tested on both enveloped (herpesviruses HSV, PRV and vesicular stomatitis VSV) and non-enveloped (MVM) viruses. The EPSp was efficient at inhibiting viral entry for the herpesviruses and VSV but was not effective against non-enveloped viruses. The in vivo assay of the EPSp in mice showed no signs of toxicity which could allow for its application in the healthcare sector.
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Antivirales/aislamiento & purificación , Antivirales/farmacología , Bacillus licheniformis/química , Matriz Extracelular de Sustancias Poliméricas/química , Virus/efectos de los fármacos , Animales , Antivirales/química , Línea Celular Tumoral , Chlorocebus aethiops , Glicerofosfatos/química , Células HeLa , Herpesviridae/efectos de los fármacos , Herpesviridae/fisiología , Humanos , Microscopía Electrónica de Rastreo , Peso Molecular , Ácido Poliglutámico/química , Polisacáridos/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectroscopía Infrarroja por Transformada de Fourier , Células Vero , Internalización del Virus/efectos de los fármacosRESUMEN
Herpes simplex virus type 1 (HSV-1) is a ubiquitous infectious agent that can establish latency in neurons, and in some cases, viral retrograde transport results in infection of the central nervous system (CNS). Several antivirals have been identified with the ability to inhibit HSV-1 replication in human cells to a greater or lesser degree, most of which are nucleoside analogues that unfortunately exhibit teratogenic potential, embryotoxicity, carcinogenic or antiproliferative activities and resistances in immunocompromised patients, specially. In the present study, we assessed two amidic derivatives of valproic acid (VPA) - valpromide (VPD) and valnoctamide (VCD) - which are already used in clinic treatments, as feasible HSV-1 antivirals in glial cells. Both VPD and VCD have exhibited increased efficacy in bipolar disorders and as anticonvulsant drugs compared to VPA, while being less teratogenic and hepatotoxic. Cytotoxicity assays carried out in our laboratory showed that VPD and VCD were not toxic in a human oligodendroglioma cell line (HOG), at least at the concentrations established for human treatments. Infectivity assays showed a significant inhibition of HSV-1 infection in HOG cells after VPD and VCD treatment, being more pronounced in VPD-treated cells, comparable to the effects obtained with acyclovir. Furthermore, the same antiherpetic effects of VPD were observed in other oligodendrocytic cell lines and rat primary oligodendrocytes (OPCs), confirming the results obtained in HOG cells. Altogether, our results allow us to propose VPD as a potential antiherpetic drug that is able to act directly on oligodendrocytes of the CNS.
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Amidas/farmacología , Antivirales/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Oligodendroglía/virología , Ácido Valproico/análogos & derivados , Amidas/química , Animales , Antivirales/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Estructura Molecular , Oligodendroglía/efectos de los fármacos , Ratas , Ácido Valproico/química , Ácido Valproico/farmacología , Proteínas Virales/genética , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVES: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). MATERIAL AND METHODS: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. All men with PCA3 ≥35 underwent an initial biopsy (IBx) -12 cores-. Men with PCA3 <35 were randomized 1:1 to either IBx or observation. We compared them to those obtained with ERSPC RC-3. RESULTS: PCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(-) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P<.001). In the PCA3(+) arm (n=301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (P<.001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89 to 56 patients). Moreover, if we had applied PCA3-35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. CONCLUSIONS: When PCA3-35 is used as a second-line biomarker when PSA ≥3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 <35.
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Antígenos de Neoplasias/orina , Biomarcadores de Tumor/orina , Detección Precoz del Cáncer , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/orina , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.
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Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Biomarcadores de Tumor/genética , HumanosRESUMEN
Valproic acid (VPA) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. VPA modulates different processes of cell metabolism that can lead to alterations in susceptibility of several cell types to the infection of Human Immunodeficiency Virus (HIV), Epstein-Barr virus (EBV), as well as to exert an inhibitory effect on the replication of different enveloped viruses in cultured cells. Taken these data into account and the fact that HSV-1 has been involved in some neuropathies, we have characterized the effect of VPA on this herpesvirus infection of the differentiation/maturation-inducible human oligodendrocyte cell line HOG, which resulted more susceptible to VPA inhibition of virus growth after cell differentiation. In these cells, the role of VPA in virus entry was tackled. Incubation with VPA induced a slight but reproducible inhibition in the virus particles uptake mainly observed when the drug was added in the adsorption or early upon infection. In addition, transcription and expression of viral proteins were significantly downregulated in the presence of VPA. Remarkably, when the infective viral production was assessed, VPA dramatically blocked the detection of infectious HSV-1 particles. Herein, our results indicate that VPA treatment of HOG cells significantly reduces the effect of HSV-1 infection, virus entry and productivity without affecting cellular viability.
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Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/fisiología , Oligodendroglía/virología , Ácido Valproico/farmacología , Replicación Viral/efectos de los fármacos , Línea Celular , Células Cultivadas , Regulación Viral de la Expresión Génica/efectos de los fármacos , Humanos , Internalización del Virus/efectos de los fármacosRESUMEN
Prostate cancer (PCa) is still a main health issue, in fact it is responsible for 10% of cancer deaths across Europe. The morphology of the prostate gland makes urine an ideal sample, non invasive, for determination both diagnostic and prognostic biomarkers. We use urinary PCA3 levels to indicate a prostate biopsy, and it is the only urinary biomarkers in PCa with FDA approval for clinical use. Many other biomarkers based on the expression of specific genes of PCa are being studied and validated, for instance the fusion gene TMPRSS2-ERG with a commercial kit available, while another approach is to test the expression of a panel of genes. An emerging focus of research, which deserves attention, is miRNAs. Other newer approaches such as epigenetics, proteomics and metabolomics also would be very useful in the future for the development and validation of new biomarkers. In this paper we review the state of the art in the field of urinary biomarkers in PCa.
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Biomarcadores de Tumor/orina , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/orina , Humanos , MasculinoRESUMEN
INTRODUCTION: Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. OBJECTIVE: To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. MATERIAL AND METHOD: The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y=0.1400+0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P<.05. RESULTS: Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P=.05) and KRT20 (P=.009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. CONCLUSIONS: According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE.
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Biomarcadores de Tumor/análisis , Proteínas de la Membrana/análisis , Micrometástasis de Neoplasia , Proteínas de Neoplasias/análisis , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/patología , Anciano , Biomarcadores de Tumor/genética , Femenino , Humanos , Queratina-20/análisis , Queratina-20/genética , Metástasis Linfática , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Valor Predictivo de las Pruebas , ARN Mensajero/análisis , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
OBJECTIVES: To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. MATERIALS AND METHODS: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. RESULTS: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume>0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). CONCLUSIONS: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.
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Educación del Paciente como Asunto , Neoplasias de la Próstata/terapia , Espera Vigilante , Adulto , Anciano , Protocolos Clínicos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. MATERIAL AND METHODS: We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with >10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA >3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12cores-. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. Re-biopsy(16-18 cores) criteria were PSA increase >.5 ng/ml at 4-6 months or PSAv > .75 ng/ml/year. RESULTS: With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P<.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P<.001). Area under the curve for PSA and PCA3 were .601 and .74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment. CONCLUSIONS: PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa.
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Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Biopsia , Humanos , Masculino , Estudios ProspectivosRESUMEN
INTRODUCTION: Patients with cutaneous melanoma who are carriers of polymorphisms in the melanocortin 1 receptor gene (MC1R) have distinctive clinical characteristics. The objective of this study was to determine the clinical characteristics associated with differing degrees of functional impairment of the melanocortin 1 receptor, as determined by the number and type (R and r) of MC1R polymorphisms. MATERIAL AND METHODS: In total, 1044 consecutive patients with melanoma diagnosed in our hospital after January 2000 were selected from the melanoma database. These patients were divided into 3 groups according to a score based on nonsynonymous MC1R polymorphisms. The frequencies of epidemiologic, phenotypic, and histologic variables and personal and family history of cancer were compared. RESULTS: Patients with a score of 3 or more were more likely to develop melanoma before the age of 50 years (odds ratio [OR]=1.47), have a tumor on the head or neck (OR=3.04), have a history of basal cell carcinoma or cutaneous squamous cell carcinoma (OR=1.70), have atypical nevi (OR=1.74), and have nevi associated with the melanoma (OR=1.87). CONCLUSIONS: The use of a scoring system for MC1R polymorphisms allowed us to identify associations between the degree of functional impairment of the melanogenesis pathway and the clinical characteristics of the patients and melanoma presentation.
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Melanoma/diagnóstico , Melanoma/genética , Polimorfismo Genético , Receptor de Melanocortina Tipo 1/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Adulto , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS) member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup. We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% (P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.
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Reordenamiento Génico/genética , Hibridación Fluorescente in Situ , Proteínas de Fusión Oncogénica/genética , Neoplasias de la Próstata/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Demografía , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/patologíaRESUMEN
The great number of biomarkers basic research is presenting in different clinical scenarios of prostate cancer demands the scientific community rigor in their molecular and clinical development for the selection of those which could supply diagnostic and prognostic information for the established nomograms of clinical-pathological factors. Prostate cancer, due to its prevalence and heterogeneity, needs a more directed diagnosis, characterization of malignant potential and monitoring of its multiple therapies. In this review article we try to go over the recent incorporation of new serum and urine markers in the clinical management of this tumor, emphasizing those with greater clinical development.
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Biomarcadores/sangre , Biomarcadores/orina , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Animales , Antígenos de Neoplasias/genética , Antineoplásicos/uso terapéutico , Biopsia , Hormonas/uso terapéutico , Humanos , Masculino , Biología Molecular , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Antígeno Prostático Específico/análisis , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/orinaRESUMEN
In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GEICO), the first "Treatment Guidelines in Ovarian Cancer" were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308-316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750-755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript.
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Neoplasias Ováricas/terapia , Conferencias de Consenso como Asunto , Femenino , Guías como Asunto , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , EspañaRESUMEN
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The present review evaluates the most important parameters in GIST: epidemiology, principal clinical presentations, histopathological patterns of GIST with differential diagnosis and Fletcher's and Miettinen's risk classification, immunohistochemistry, prognostic factors, c-KIT and PDGFRalpha mutations and treatment of this tumor. The most frequent site for GISTs is the stomach, followed by the duodenum and small intestine; spindle cell morphology is described in 70% with CD17 positivity in around 95% of the cases; exon 11 of c-KIT is the most mutated, with Gleevec being the principal treatment. In GISTs, high mitotic rate, large tumor size, incomplete resection, extragastrointestinal site, duplication 502-503 in exon 9 of c-KIT, and secondary mutations are negative prognostic factors.
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Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Diagnóstico Diferencial , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Tasa de SupervivenciaRESUMEN
OBJECTIVES: DD3(PCA3) (PCA3) gene expression is prostate cancer-specific. Routine use of this biomarker has resulted in a 35-67% reduction in the number of required biopsies. The aim of this study is to evaluate our outcomes in its routine use and to establish in which group of patients this is the most efficient, depending on the number of previous PCA3 biopsies. MATERIAL AND METHODS: A total of 474 consecutive patients who had previously undergone a biopsy (group A, n=337) or not (group B, n=134) for whom a PCA3 was requested were analyzed. We subdivided group A into A(1) (a previous biopsy, n=182) and A(2) (<1 previous biopsy, n=155). The recommendation of whether to perform a biopsy or not was made independently by each of the 11 clinicians and guided by prostatic specific antigen (PSA) levels and digital rectal examination. RESULTS: Median age was 65 years (range 38 to 84). PCA3 score had an informative ratio of 99.6%, with a median of 29 (range 1-3245). The percentage of biopsy sparing was 49% of the cases. ROC analysis demonstrated an AUC for PSA and PCA3 of 0.532 (P=.417) and 0.672 (P<.0001), respectively. Sensitivities of PSA≥ 4 and PCA3≥ 35 were 87% vs. 85%, with specificities of 12% vs. 33%, PPV 34% vs. 39% and NPV 63% vs. 81%, respectively. The PCA3 score showed direct correlation with the percentage of positive biopsies (P<.0001). CONCLUSIONS: Routine use of PCA3, due to its high NPV, results in a significant reduction in the number of biopsies. PCA3 appears to be more efficient in biopsy-naive patients. Among patients already biopsied, the results are superior in those biopsied only once.
Asunto(s)
Adenocarcinoma/orina , Antígenos de Neoplasias/orina , Biomarcadores de Tumor/orina , Neoplasias de la Próstata/orina , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Biopsia con Aguja/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , ARN Mensajero/análisis , Curva ROC , Juego de Reactivos para Diagnóstico/estadística & datos numéricos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , España/epidemiologíaRESUMEN
BACKGROUND: TMPRSS2-ETS fusion gene rearrangements constitute a very common and specific alteration in prostate cancer cells. These genetic alterations lead the overexpression of ETS genes which encode the E26 family of transcription factors involved in cell proliferation. Of this family, the ERG oncogene is overexpressed in almost 50% of prostate cancer cases. EVIDENCE SYNTHESIS: TMPRSS2-ERG overexpresses ERG through an androgen-mediated response. Structurally, the rearrangement is due to interstitial deletion and to a lesser extent to reciprocal translocation and plays a key role in cellular metabolism. Almost all fusion gene transcripts produce a truncated ERG protein and the presence of a specific isoform of this gene suggests the clonality of the tumor; hence, metastasis shares the fusion gene status of their primary lesion. Although the prognostic implications of TMPRSS2-ERG have not been fully elucidated, they constitutes a field of great diagnostic potential and, therefore, the development of techniques to identify and to analyze the presence and characteristics of this gene in a non-invasive fashion deserves great interest in this area. Currently, there is evidence supporting the hypothesis that the presence of fusion gene differentiates two molecular groups within prostate cancer with a differential behaviour making the fusion gene a potential therapeutic target. In this regard, the use of anti-HDAC (trichostatin), antagonists of estrogen receptor alpha and abiraterone acetate have shown promising results. CONCLUSIONS: This review describes the great potential offered by the investigation of fusion genes in PC and the need for further studies.