Neoplasia papilar de polaridad inversa: un nuevo subtipo de tumor renal de buen pronóstico / Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis

Introducción: La neoplasia papilar renal de polaridad inversa (NPRPI) ha sido recientemente reconocida como una entidad separada de la clasificación tradicional de los carcinomas papilares de células renales por sus peculiares características histopatológicas, inmunofenotípicas y moleculares, y un comportamiento indolente. Material y métodos: En este trabajo aportamos 6 nuevos casos y realizamos una revisión de la literatura publicada al respecto hasta el momento actual, recopilándose un total de 104 casos. Resultados: Nuestros casos de NPRPI corresponden a 5 hombres y una mujer, con edades comprendidas entre los 47 y los 91 años. En 5 casos la NPRPI resultó un hallazgo incidental en piezas de nefrectomía indicada por la presencia de otro tumor renal y en uno la NPRPI fue el motivo de la intervención quirúrgica. Nuestros casos presentan tamaños entre los 2 y los 13mm, y una histología papilar con revestimiento en monocapa de células eosinófilas con núcleos de bajo grado en localización apical. Inmunohistoquímicamente muestran una constante positividad para GATA3 y negatividad para vimentina. Se identificaron mutaciones en KRAS en el 50% de ellos. Tras un seguimiento comprendido entre uno y 60 meses, 5 de los pacientes seguían vivos sin recurrencia o metástasis y uno falleció a causa de un carcinoma urotelial. Conclusiones: Nuestros casos concuerdan con las características clínicas y patológicas descritas en los publicados hasta el momento. Aportamos la primera serie nacional y corroboramos la existencia de unos criterios diagnósticos definidos y constantes que permiten considerar la NPRPI como una entidad propia distintiva. (AU)

Introduction: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior . Material and methods: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. Results: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. Conclusions: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity. (AU)

Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis.

INTRODUCTION: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. MATERIAL AND METHODS: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. RESULTS: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. CONCLUSIONS: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.

Fotoféresis extracorpórea en enfermedad injerto contra huésped en una población pediátrica / Extracorporeal Photopheresis in Pediatric Graft-vs-Host Disease

Antecedentes La fotoféresis extracorpórea (FEC) es una terapia inmunomoduladora indicada para la enfermedad injerto contra huésped (EICH) en adultos y niños, no obstante, existen pocos estudios en esta última población. Objetivo Describir las características demográficas, la respuesta clínica, los efectos adversos y la evolución de los pacientes pediátricos con EICH aguda (EICH-a) y EICH crónica (EICH-c) tratados con FEC. Materiales y métodos Se incluyeron todos los pacientes con EICH-a y EICH-c sometidos a tratamiento con FEC entre enero de 2012 y diciembre de 2018 en el Servicio de Dermatología del Hospital Italiano de Buenos Aires. Se utilizó el sistema UVAR-XTS™ en 2 pacientes y el CELLEX™ en el resto, con 2 sesiones por semana y reevaluación al mes en EICH-a, 2 sesiones cada 2 semanas con reevaluación a los 3 meses en EICH-c, y en ambos finalización según respuesta. Resultados Evaluamos 9 pacientes pediátricos con EICH refractaria, dependiente y/o resistente a corticoides sistémicos tratados con FEC. Siete pacientes fueron respondedores y 2 no respondedores. La piel presentó respuesta completa (RC) en 1/9 y respuesta parcial en 7/9 pacientes, el hígado, el sistema gastrointestinal y las mucosas presentaron RC en 3/5, 1/2 y 4/5 pacientes, respectivamente. Dos pacientes fallecieron durante el periodo estudiado. Conclusión La FEC es una buena opción terapéutica para los pacientes pediátricos con EICH aguda y crónica (AU)

Background Extracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children. Objective To describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP. Material and methods We included all pediatric patients with acute or chronic GVHD treated with ECP by the Dermatology Department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response. Results We evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period. Conclusion ECP is a good treatment option for pediatric patients with acute or chronic GVHD (AU)

Extracorporeal Photopheresis in Pediatric Graft-vs-Host Disease.

BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children. OBJECTIVE: To describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP. MATERIAL AND METHODS: We included all pediatric patients with acute or chronic GVHD treated with ECP by the dermatology department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response. RESULTS: We evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period. CONCLUSION: ECP is a good treatment option for pediatric patients with acute or chronic GVHD.

Extracorporeal Photopheresis in Pediatric Graft-vs-Host Disease. / Fotoféresis extracorpórea en enfermedad injerto contra huésped en una población pediátrica.

BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children. OBJECTIVE: To describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP. MATERIAL AND METHODS: We included all pediatric patients with acute or chronic GVHD treated with ECP by the Dermatology Department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response. RESULTS: We evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period. CONCLUSION: ECP is a good treatment option for pediatric patients with acute or chronic GVHD.

Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies. / Utilidad de GATA-3 como marcador de epitelio seminal en las biopsias de próstata.

OBJECTIVES: The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. MATERIAL AND METHODS: Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. RESULTS: Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. CONCLUSIONS: The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas.

Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil.

Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil.

Approximately 200 million people suffer from type 2 diabetes (T2D) worldwide, and the rapid increase in the prevalence of this disease is likely a result of multiple environmental factors, such as increased food intake and decreased physical activity in genetically predisposed individuals. Different population studies have demonstrated a strong association of two polymorphic variations in the TCF7L2 gene, the noncoding single nucleotide polymorphisms (SNPs) rs7903146 (C/T) and rs12255372 (G/T), with T2D. Herein, we analyzed the association of these SNPs with T2D in a population from northeastern Brazil. Our results showed that the genotype and allele frequencies in TCF7L2 rs7903146 and rs12255372 were similar in the patient and control groups (P > 0.05). In addition, the allele frequencies were not significantly associated with T2D risk [rs7903146: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.52-1.76, P = 1.00, and rs12255372: OR = 1.38, 95%CI = 0.72-2.62, P = 0.41]. These data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population. However, our results may reflect the small number of subjects. Alternatively, these results may be attributable to specific ethnic effects, as most of the previously reported associations were demonstrated with predominantly European populations. To reach a definitive conclusion on the role of such gene variants for T2D in mixed populations, additional efforts are necessary to replicate this study with larger populations from areas with more ethnic heterogeneity.

Prevalence of variants that confer risk for venous thromboembolism in an elderly population of northeastern Brazil.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality stemming from cardiovascular disease. It is a multifactorial disease caused by a combination of acquired risk factors, of which advanced age is the most significant, and genetic factors, including the variants FV G1691A, FII G20210A, and MTHFR C677T. We estimated the prevalence of these genomic variants in an elderly population of northeastern Brazil. The study included 188 elderly persons (65-93 years), of which 68 (36.2%) were men and 120 (63.8%) were women. Variants were detected by polymerase chain reaction-restriction fragment length polymorphism analysis, and subsequent electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. The study population was in Hardy-Weinberg equilibrium for the 3 loci. Of the individuals analyzed, none carried variants of FV or FII (0%), and 24.7% had the MTHFR C677T polymorphism: 59 subjects (31.4%) were heterozygous (CT) and 17 subjects (9%) were homozygous (TT). Based on the analysis of these particular genes, we conclude that the study population does not present an increased risk for the development of VTE. Faced with a growing aging population worldwide, similar studies in other countries will help in the prevention of VTE in older individuals.

Interobserver reproducibility of a grading system for chromophobe renal cell carcinoma.

OBJECTIVES: To evaluate interobserver reproducibility of a grading system proposed by Paner et al. for chromophobe renal cell carcinoma. MATERIAL AND METHODS: After selecting 23 cases of chromophobe renal cell carcinoma from the Xeral-Cíes Hospital, Meixoeiro Hospital and POVISA Hospital from the last 15 years, an informative meeting on the Paner et al. grading system criteria was held. After, the participating pathologists applied the system to each case, evaluating one slide selected. Kappa index for interobserver reproducibility was calculated, and it was classified according to the Landis and Koch scale. RESULTS: The grading distribution was similar for most of the 6 participating observers, with grade 1 predominance. The remaining 2 observers considered a relatively higher proportion of grade 2. Kappa index values ranged from 0.136 to 0.674, with a discrete-moderate reproducibility index predominance (0.21-0.60). Highest Kappa value (0.674) was obtained between the most novel and the most expert interobservers. The lowest Kappa value was obtained among the most veteran pathologists (0.136). CONCLUSIONS: Interobserver reproducibility for chromophobe renal cell carcinoma is discrete-moderate in our institutions when the novel grade proposed by Paner et al. is used. Labeling of grades 1 and 2 is not homogeneous among 6 participating observers. While awaiting a grading consensus on a new classification by the scientific societies, we consider that the routine use of a grading system for chromophobe renal cell carcinoma should not be used.

Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas.

The gene XRCC3 (X-ray cross complementing group 3) has the task of repairing damage that occurs when there is recombination between homologous chromosomes. Repair of recombination between homologous chromosomes plays an important role in maintaining genome integrity, although it is known that double-strand breaks are the main inducers of chromosomal aberrations. Changes in the XRCC3 protein lead to an increase in errors in chromosome segregation due to defects in centrosomes, resulting in aneuploidy and other chromosomal aberrations, such as small increases in telomeres. We examined XRCC3 Thr241Met polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. The individuals of the control group (N = 100) were selected from the general population of the São Paulo State. Odds ratio and 95%CI were calculated using a logistic regression model. Patients who had the allele Met of the XRCC3 Thr241Met polymorphism had a significantly increased risk of tumor development (odds ratio = 3.13; 95% confidence interval = 1.50-6.50). There were no significant differences in overall survival of patients. We suggest that XRCC3 Thr241Met polymorphism is involved in susceptibility for developing astrocytomas and glioblastomas.

Analysis of the polymorphisms XRCC1Arg194Trp and XRCC1Arg399Gln in gliomas.

XRCC genes (X-ray cross-complementing group) were discovered mainly for their roles in protecting mammalian cells against damage caused by ionizing radiation. Studies determined that these genes are important in the genetic stability of DNA. Although the loss of some of these genes does not necessarily confer high levels of sensitivity to radiation, they have been found to represent important components of various pathways of DNA repair. To ensure the integrity of the genome, a complex system of DNA repair was developed. Base excision repair is the first defense mechanism of cells against DNA damage and a major event in preventing mutagenesis. Repair genes may play an important role in maintaining genomic stability through different pathways that are mediated by base excision. In the present study, we examined XRCC1Arg194Trp and XRCC1Arg399Gln polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. Patients who had the allele Trp of the XRCC1Arg194Trp polymorphism had an increased risk of tumor development (OR = 8.80; confidence interval at 95% (95%CI) = 4.37-17.70; P < 0.001), as did the allele Gln of XRCC1Arg399Gln (OR = 1.01; 95%CI = 0.53-1.93; P = 0.971). Comparison of overall survival of patients did not show significant differences. We suggest that XRCC1Arg194Trp and XRCC1Arg399Gln polymorphisms are involved in susceptibility for developing astrocytomas and glioblastomas.

GSTP1 Ile105Val polymorphism in astrocytomas and glioblastomas.

Glutathione S-transferases (GSTs) constitute a superfamily of ubiquitous multifunctional enzymes that are involved in the cellular detoxification of a large number of endogenous and exogenous chemical agents that have electrophilic functional groups. People who have deficiencies in this family of genes are at increased risk of developing some types of tumors. We examined GSTP1 Ile105Val polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. Patients who had the Val allele of the GSTP1 Ile105Val polymorphism had an increased risk of tumor development (odds ratio = 8.60; 95% confidence interval = 4.74-17.87; P < 0.001). Overall survival of patients did not differ significantly. We suggest that GSTP1 Ile105Val polymorphisms are involved in susceptibility to developing astrocytomas and glioblastomas.

Livedoid vasculopathy and recurrent thrombosis in a patient with lupus: seronegative antiphospholipid syndrome?

Livedoid vasculopathy is a rare condition which predominantly affects young women. It is characterized by intense painful purpuric maculae in the legs, ankles and feet, due to thrombosis of the small and medium-sized dermal vessels, in the absence of vasculitis. Livedoid vasculopathy has been frequently associated with hypercoagulable states and antiphospholipid syndrome. We describe a 34-year-old White woman suffering from systemic lupus erythematosus, livedo reticularis, haemolytic anaemia, severe thrombocytopenia and recurrent venous thrombosis who was admitted to the hospital for extremely painful purpuric lesions in her lower limbs. The clinical and histological findings were diagnostic of livedoid vasculopathy. Once the initial sub-therapeutic international normalized ratio levels were corrected, livedoid vasculopathy did not recur. Tests for antiphospholipid antibodies were repeatedly negative. This case, the first reported of livedoid vasculopathy in a patient with seronegative antiphospholipid syndrome and systemic lupus erythematosus, draws attention to livedoid vasculopathy, a thrombotic dermopathy that may be under-diagnosed in patients with antiphospholipid syndrome.

[Squamous cell carcinoma arising on an epidermal inclusion cyst: a case presentation and review of the literature]. / Carcinoma epidermoide desarrollado sobre quiste de inclusión epidérmica cutáneo. Presentación de un nuevo caso y revisión de la literatura.

Epidermal inclusion cysts are very common lesions that very rarely undergo malignant transformation-in the English-language literature we have only found 18 adequately documented cases. We present the case of a man with a 2-month history of a retroauricular skin lesion in which histological study revealed squamous cell carcinoma arising on an epidermal inclusion cyst. Cysts that grow rapidly, reach a large size, ulcerate, develop a fistula, or that do not respond to medical treatment, and those that recur should be excised completely and histological study performed of the whole lesion.

Concurrent sequence variation of TP53 and TP73 genes in anaplastic astrocytoma.

Disruption or loss of tumor suppressor gene TP53 is implicated in the development or progression of almost all different types of human malignancies. Other members of the p53 family have been identified. One member, p73, not only shares a high degree of similarity with p53 in its primary sequence, but also has similar functions. Like p53, p73 can bind to DNA and activate transcription. Using PCR-SSCP and gene sequencing, we analyzed the TP53 and TP73 genes in a case of a grade III anaplastic astrocytoma that progressed to glioblastoma. We found a deletion of AAG at position 595-597 of TP53 (exon 6), resulting in the deletion of Glu 199 in the protein and a genomic polymorphism of TP73, identified as an A-to-G change, at position E8/+15 at intron 8 (IVS8-15A>G). The mutation found at exon 6 of the gene TP53 could be associated with the rapid tumoral progression found in this case, since the mutated p53 may inactivate the wild-type p53 and the p73alpha protein, which was conserved here, leading to an increase in cellular instability.

Identificación de alteraciones genéticas en oligodendrogliomas mediante amplificacióndependiente de ligasa de múltiples sondas (MLPA) (multiple ligationdependentprobe amplification) / Identification of genetic alterations by multiple ligation- dependent probe amplification (MLPA) analysis in oligodendrogliomas

La alteración genética más frecuente en oligodendrogliomases la pérdida conjunta de lp/19q. Este eventoya acontece en etapas primarias del desarrollo deestos tumores. Es de gran valor clínico conocersi dichos tumores poseen esta deleción ya que seha correlacionado con un mejor pronóstico de lospacientes. Además de esta alteración. también se haobservado la deleción de CDKN2A y PTEN y la amplificaciónde EGFR; estos cambios parecen asociarse auna mayor agresividad tumoral. Mediante la técnicade MLPA en una misma reacción podemos determinarsi existe pérdida de lp/19q y deleciones/amplificacionesde los genes anteriormente mencionados en el ADNprocedente de muestras tumorales. En este trabajohemos analizado 40 oligodendrogliomas y el kit MLPAP088 para determinar el estado alélico de lp/19q, asícomo el kit MLPA P105 para observar la amplificación/deleción de los genes CDKN2A, PTEN, ERBB2, TP53 yEGFR. Mostraron pérdida de 1p el 45% de los tumores(18/40) y el 65% (26/40) de los oligodendrogliomaspresentaron deleción de las sondas que hibridan en lasregiones de 19q. Para el kit MLPA P105, mostraronduplicación/deleción de EGFR en el 7,5% (3/41) y 35%(14/40) de las muestras, respectivamente. El 60% de loscasos (24/40) mostraron deleción de CDKN2 y ningunamuestra presentó duplicación de las sondas para estegen. El gen ERBB2 se presentó duplicado en el 12,5%de los tumores (5/40) y un único tumor mostró pérdidasde dicho gen. El 30% (12/40) de las muestras presentódeleción para PTEN y el 12,5% (5/40) mostró duplicaciónde dicho gen y, por último, 12,5% de los casos(5/40) presentaron duplicaciones de TP53. Estos resultadosindican que la técnica de MLPA es idónea para laidentificación de las alteraciones moleculares característicasde oligodendrogliomas. Estas alteraciones estaríancontribuyendo a la formación del tumor, siendola anomalía más significativa en oligodendrogliomas la (...) (AU)

Concurrent deletion at 1p/19q is a common signatureof oligodendrogliomas, and it may be identified inlow-grade tumours (grade II) suggesting it representsan early event in the development of these brain neoplasms.Additional non-random changes primarilyinvolve CDKN2A, PTEN and EGFR. Identification ofall of these genetic changes has become an additionalparameter in the evaluation of the clinical patients' prognosis, including good response to conventional chemotherapy.Multiple ligation-dependent probe amplification(MLPA) analysis is a new methodology thatallows an easy identification of the oligodendrogliomas'abnormalities in a single step. No need of the respectiveconstitutional DNA from each patient is anotheradvantage of this method. We used MLPA kits P088and P105 to determine the molecular characteristics ofa series of 40 oligodendrogliomas. Deletions at l p and19q were identified in 45% and 65% of cases, respectively.Alterations of EGFR, CDKN2A, ERBB2, PTENand TP53 were also identified in variable frequenciesamong 7% to 35% of tumours. These findings demonstratethat MLPA is a reliable technique to the detectionof molecular genetic changes in oligodendrogliomas (AU)

Polymorphisms and DNA methylation of gene TP53 associated with extra-axial brain tumors.

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer; this gene is mutated in up to 50% of human tumors. It has a critical role in the cell cycle, apoptosis and cell senescence, and it participates in many crucial physiological and pathological processes. Polymorphisms of p53 have been suggested to be associated with genetically determined susceptibility in various types of cancer. Another process involved with the development and progression of tumors is DNA hypermethylation. Aberrant methylation of the promoter is an alternative epigenetic change in genetic mechanisms, leading to tumor suppressor gene inactivation. In the present study, we examined the TP53 Arg72Pro and Pro47Ser polymorphisms using PCR-RFLP and the pattern of methylation of the p53 gene by methylation-specific PCR in 90 extra-axial brain tumor samples. Patients who had the allele Pro of the TP53 Arg72Pro polymorphism had an increased risk of tumor development (odds ratio, OR = 3.23; confidence interval at 95%, 95%CI = 1.71-6.08; P = 0.003), as did the allele Ser of TP53 Pro47Ser polymorphism (OR = 1.28; 95%CI = 0.03-2.10; P = 0.01). Comparison of overall survival of patients did not show significant differences. In the analysis of DNA methylation, we observed that 37.5% of meningiomas, 30% of schwannomas and 52.6% of metastases were hypermethylated, suggesting that methylation is important for tumor progression. We suggest that TP53 Pro47Ser and Arg72Pro polymorphisms and DNA hypermethylation are involved in susceptibility for developing extra-axial brain tumors.

[Effect of double anaesthetic Colicursi (tetracaine 0.1% and oxybuprocaine 0.4%) on central and paracentral corneal thickness]. / Efecto de la instilación del colicursi anestésico doble (tetracaína 0,1% y oxibuprocaína 0,4%) sobre el espesor corneal central y paracentral.

OBJECTIVE: To study the effect of 1 drop of combined topical anaesthesia (tetracaine 0.1% and oxybuprocaine 0.4%) on central corneal thickness (CCT) values and at 2.5 mm from the corneal centre in nasal, temporal, superior and inferior hemi meridians, monitored by Orbscan over a period of 16 minutes. MATERIALS AND METHODS: The corneal thickness of 12 right eyes of 12 young healthy men was determined using the Orbscan Topography System. Values were determined at the centre and paracentral regions 2.5 mm from the centre every 2 minutes for 16 minutes before and after the administration of 1 drop of double anaesthetic Colircusi which contains tetracaine 0.1% and oxybuprocaine 0.4%. RESULTS: There was no obvious trend of central and paracentral corneal thickness value change before and after administration of Colircusi (paired ANOVA, p>0.05). Although corneal thickness variation was not statistically significant, higher differences were observed at the 6 minute time-point for CCT and at 8 minutes for nasal paracentral corneal thickness. CONCLUSIONS: One drop of double anaesthetic Colircusi with tetracaine 0.1% and oxibuprocaine 0.4% does not produce any significant change in central corneal thickness or in paracentral regions 2.5 mm from the centre (nasal, temporal, superior and inferior hemi meridians).

DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.(AU)