Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

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.

The hallmarks of ovarian cancer: Focus on angiogenesis and micro-environment and new models for their characterisation.

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.

LEACHING AND DEGRADATION OF 2,4-DICHLOROPHENOXIACETIC ACID, IN COLOMBIA RICE FLOODED SOIL.

Rice is mostly cultivated on soil held under flooded conditions. Under these conditions pesticides undergo reductive transformations which are characteristic to rice fields and other anaerobic systems. The present study was undertaken to evaluate the mobility and persistence of 2,4-dichlorophenoxy acetic acid (2,4-D) under laboratory conditions for the rice crop in Espinal, Colombia. A displacement study was performed on a hand packed soil column 30 cm length. After leaching experiment, the soil from column was sliced into six successive sections (5 cm). Methanol acidified (H3PO4 0.25%) extraction was used to determine the herbicide residues in each section. 2,4-D experimental breakthrough curve was analyzed using Stanmod program (inverse problem) to obtain transport parameters. The non-equilibrium physical model fitted well the experimental breakthrough curve. The recovery percent of 2,4-D in leachates was 36.44% after 3.4 pore volumes, and retardation factor was 2.1, indicating low adsorption in that conditions. 2,4-D was rapidly degraded, with DT50 = 11.4 days. The results suggest that 2,4-D under flooded conditions have a high potential for leaching through the soil profile, although the elevated rate of degradation reduced the ground water contamination risk.

Clinical characteristics of patients with cutaneous melanoma according to variants in the melanocortin 1 receptor gene.

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.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

First Report of Shoot Blight and Canker Caused by Diplodia coryli in Hazelnut Trees in Chile.

Shoot blight, twig and branch cankers with grayish discoloration, roughened tissue, and dieback were observed in 5-year-old European hazelnut trees (Corylus avellana L.) cv. Barcelona at two commercial plantations in the Allipén locality, Region de La Araucanía (38° 59' 24.76″ S, 72° 29' 35.58″ W), Chile, during the 2011 to 2012 growing season. In addition, discoloration of the wood was observed in cross-sections. In order to isolate the causal agent, entire twigs and shoot fragments with cankers were sterilized in 0.5% sodium hypochlorite for 2 minutes, followed by two rinses with sterile distilled water. The tissues were then stored in a humid chamber. Sub-epidermal black pycnidia with sporulation were detected on the symptomatic tissue. Conidia were transferred to potato dextrose agar (PDA) (Difco, Lawrence, KS) and incubated at 25°C in the dark. The mycelia were black, creeping, and compact in appearance. The mature conidia were dark brown with a single septum, slightly constricted at the septum, and ovoid with a broadly rounded apex; some had a truncated base. Conidia had the following measurements: (20.0-) 23.1 ± 1.9 (-28.0) × (10-) 11.9 ± 1.2 (-15) µm with an average length/width ratio of 1.95 ± 0.17 (n = 50). These morphometric characteristics correspond to those of Diplodia coryli Fuckel (1870), teleomorph: Botryosphaeria sensu lato. The identity of the fungus was confirmed using internal transcribed spacer (ITS) rDNA sequencing completed at CABI, United Kingdom. The sequencing report indicated that the isolate (IMI-501235a) had 100% homology with a reference strain (CBS 242.51) in the CBS collection. The obtained sequence was deposited in GenBank (Accession No. JX163116). The anamorphs of Botryosphaeria have been divided into up to 18 genera (1), many of which are not clearly defined. Diplodia (3), including D. coryli (CBS 242.51) and D. juglandis (CBS 188.87), have been included within the genus Dothiorella (2), but the taxon names have not been formally changed. A pathogenicity test was conducted with one isolate (IMI-501235a) and four 1-year-old plants of hazelnut cultivar Barcelona. Plants were maintained in individual bags in greenhouse conditions (14/10 hours dark/light, 20°C; 70% RH). Prior to inoculation, plant tissues were externally disinfected with sodium hypochlorite (2%) and rinsed with sterile distilled water. Each plant was inoculated at fresh wound sites on two shoots and three twigs around each vegetative bud. The inoculum consisted of an agar plug with mycelia (5 mm) from the margin of an actively growing colony cultured on PDA media for 7 days. Each wound was covered with moistened cotton and sealed with Parafilm; a control plant was inoculated in the same way with agar only. After 3 months, fragments of necrotic and discolored vascular system tissues from inoculated shoots were removed and incubated on PDA. D. coryli was consistently recovered from these tissues, satisfying Koch's postulates. The control plant showed no symptoms of the disease. D. coryli has been reported to cause symptoms of dieback (dead branches) in Italy and Spain. To our knowledge, this is the first report of D. coryli on C. avellana cv. Barcelona in Chile. European hazelnut is an emerging crop in Chile, grown mainly for export, and management strategies for this disease will need to be developed. References: (1) S. Denman et al. Stud. Mycol. 45:129, 2000. (2) A. J. L. Phillips et al. Persoonia 21:29, 2008. (3) A. J. L. Phillips et al. Mycologia 97:513, 2005.

[Non-invasive diagnosis of prostate cancer: serum and urine markers]. / Diagnóstico no invasivo del cáncer de próstata; marcadores séricos y en orina.

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.

Influence of plasma kinetic energy during the pulsed laser deposition of borophene films on silicon (100).

Developing borophene films with good structural stability on non-metallic substrates to maximize their potential in photosensitivity, gas detection, photothermia, energy storage, and deformation detection, among others has been challenging in recent years. Herein, we succeeded in the pulsed laser deposition of multilayered borophene films on Si (100) with ß12 or χ3 bonding by tuning the mean kinetic energy in the plasma during the deposition process. Raman and X-ray photoelectron spectroscopies confirm ß12 and χ3 bonding in the films. Borophene films with ß12 bonding were obtained by tuning a high mean kinetic energy in the plasma, while borophene with χ3 bonding required a relatively low mean kinetic energy. Atomic force microscopy (AFM) micrographs revealed a granular and directional growth of the multilayered borophene films following the linear atomic terraces from the (100) silicon substrate. AFM nanofriction was used to access the borophene surfaces and to reveal the pull-off force and friction coefficient of the films where the surface oxide showed a significant contribution. To summarize, we show that it is possible to deposit multilayered borophene thin films with different bondings by tuning the mean kinetic energy during pulsed laser deposition. The characterization of the plasma during borophene deposition accompanies our findings, providing support for the changes in kinetic energy.

An efficient nonstandard computer method to solve a compartmental epidemiological model for COVID-19 with vaccination and population migration.

BACKGROUND AND OBJECTIVE: In this manuscript, we consider a compartmental model to describe the dynamics of propagation of an infectious disease in a human population. The population considers the presence of susceptible, exposed, asymptomatic and symptomatic infected, quarantined, recovered and vaccinated individuals. In turn, the mathematical model considers various mechanisms of interaction between the sub-populations in addition to population migration. METHODS: The steady-state solutions for the disease-free and endemic scenarios are calculated, and the local stability of the equilibium solutions is determined using linear analysis, Descartes' rule of signs and the Routh-Hurwitz criterion. We demonstrate rigorously the existence and uniqueness of non-negative solutions for the mathematical model, and we prove that the system has no periodic solutions using Dulac's criterion. To solve this system, a nonstandard finite-difference method is proposed. RESULTS: As the main results, we show that the computer method presented in this work is uniquely solvable, and that it preserves the non-negativity of initial approximations. Moreover, the steady-state solutions of the continuous model are also constant solutions of the numerical scheme, and the stability properties of those solutions are likewise preserved in the discrete scenario. Furthermore, we establish the consistency of the scheme and, using a discrete form of Gronwall's inequality, we prove theoretically the stability and the convergence properties of the scheme. For convenience, a Matlab program of our method is provided in the appendix. CONCLUSIONS: The computer method presented in this work is a nonstandard scheme with multiple dynamical and numerical properties. Most of those properties are thoroughly confirmed using computer simulations. Its easy implementation make this numerical approach a useful tool in the investigation on the propagation of infectious diseases. From the theoretical point of view, the present work is one of the few papers in which a nonstandard scheme is fully and rigorously analyzed not only for the dynamical properties, but also for consistently, stability and convergence.

The GIST paradigm: how to establish diagnostic and prognostic criteria.

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.

Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer.

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) (p = 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.

Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.

BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.

14C tebuconazole degradation in Colombian soils.

Tebuconazole is a fungicide used on onion crops (Allium Fistulosum L) in Colombia. Persistence of pesticides in soils is characterized by the half-life (DT50), which is influenced by their chemical structure, the physical and chemical properties of the soil and the previous soil history. Based on its structural and chemical properties, tebuconazole should be expected to be relatively persistent in soils. Laboratory incubation studies were conducted to evaluate persistence and bond residues of 14C tebuconazole in three soils, two inceptisol (I) and one histosol (H). Textural classifications were: loam (101), loamy sand (102) and loam (H03), respectively. Data obtained followed a first-order degradation kinetics (R2 > or = 0.899) with DT50 values between 158 and 198 days. The production of 14CO2 from the 14C-ring-labelled test chemicals was very low and increased slightly during 63 days in all cases. The methanol extractable 14C-residues were higher than aqueous ones and both decreased over incubation time for the three soils. The formation of bound 14C-residues increased with time and final values were 11.3; 5.55 and 7.87% for 101, 102 and H03 respectively. Soil 101 showed the lowest mineralization rate and the highest bound residues formation, which might be explained by the clay fraction content. In contrast, an inverse behavior was found for soils 102 and H03, these results might be explained by the higher soil organic carbon content.

Isolation and characterization of an exopolymer produced by Bacillus licheniformis: In vitro antiviral activity against enveloped viruses.

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.

An optimal Bayesian threshold method for onset detection in electric biosignals.

In this work, we consider the problem of identifying activity phases in electromyography signals, and various other potential types of electrical and non-electrical biological signals such as electroneurograms, electroencephalograms, voice and ultrasounds. The solution to this problem has been provided under relatively limited scenarios. The purpose of the present work is to propose an optimal Bayesian classifier to solve the problem of detecting bursts on biological signals. To that end, a parametrization of the distribution of samples in signals is presented. We propose a model based on a linear combination of normal distributions with mean equal to zero and different variances. The threshold criterion is expressed in a closed-form, and the use of morphology operators in the post-processing treatment leads to accurate results. Various comparisons are provided against other techniques available in the literature. In all of our experiments, we show that our present approach yields superior results.

Amidic derivatives of valproic acid, valpromide and valnoctamide, inhibit HSV-1 infection in oligodendrocytes.

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.

Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours.

AIMS: To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms. METHODS AND RESULTS: One hundred and one patients with primary bladder tumours were retrospectively analysed. Immunohistochemically, a polyclonal antibody was utilized and the level of WWOX protein expression was analysed by using a combined score system based on intensity of the reaction and percentage of immunoreactive tumour cells. WWOX protein expression was consistently expressed in non-neoplastic urothelium, whereas a progressive loss of immunoreactivity was observed as tumour grade and stage increased (P < 0.05). Principal component analysis showed that reduced WWOX immunoexpression was significantly associated with high histological grades (P = 0.001), advanced stage (P = 0.002), tumour size (P = 0.04) and cancer progression (P = 0.028). Invasive urothelial carcinomas of the bladder with squamous metaplasia presented the lowest levels of WWOX protein. Kaplan-Meier analyses demonstrated a significant correlation between loss of WWOX expression and a shorter progression-free survival (P = 0.042), whereas the prediction of overall survival achieved borderline significance (P = 0.053). CONCLUSION: Loss of WWOX immunoexpression strongly correlates with classical clinicopathological factors and appears to be a potential predictive marker of progressive disease.

Concurrent EGFR amplification and TP-53 mutation in glioblastomas.

Glioblastoma multiforme is the most common and most aggressive of the primary brain tumors. The mean survival of patients is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Cytogenetically, karyotypes of glioblastomas are very complex with trisomy 7 and monosomy 10 as the most frequent abnormalities. A genetic alteration that is significantly more frequent in primary than in secondary glioblastomas, the latter arising from preceding low-grade gliomas, is epidermal growth factor receptor gene (EGFR) amplification, whereas TP-53 mutations are significantly more frequent in low-grade gliomas and secondary glioblastomas derived there- from. We report the histological and genetic study of two glioblastomas, one case arising de novo and the other case arising 3 years after a previously diagnosed anaplastic astrocytoma, with concurrent EGFR amplification and TP-53 mutation. These anomalies were initially deemed as mutually exclusive. However, a small percentage of cases have been found with both anomalies although at a significantly lower level than could be expected. We have analyzed these two cases cytogenetically and by molecular studies in order to detect additional alterations associated with this phenotype. Cytogenetically, both cases showed in common the monosomy of chromosomes 10 and 17. At the molecular level, a rare mutation of TP-53 was found in the secondary glioblastoma and hypermethylation of the promoter region of p16(INK4a) and p14(ARF) genes were observed in the primary and secondary glioblastoma, respectively.

Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis.

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.