Are both distinct epithelial and stromal cells molecular analysis from phyllodes tumors versus fibroadenoma components affected in breast fibroepithelial progression?

Purpose: To determine molecular events involved in the tumorigenesis of phyllodes tumors (PT) and the role of each stromal (SC) and epithelial (EC) cell. Methods: Frozen breast samples enriched with epithelial and stromal cells from three fibroadenomas and 14 PT were retrieved and laser microdissected. Sanger and polymerase chain reaction-based sequencing of exon 2 MED12 and TERT promoter hotspot mutations were performed; 44K microarray platform was used to analyze gene expression. Results: All three fibroadenomas (FAs) presented mutations in MED12, but not in TERT, whose mutation was observed in five of the 14 PTs. EC and SC of each affected tumor displayed identical alterations. Of the total differentially expressed genes (DEG) (EC = 1,543 and SC = 850), 984 were EC-eDEGs and 291 were SC-eDEGs. We found a high similarity of diseases and functions enriched by both cell types, but dissimilarity in the number of enriched canonical pathways. Three signaling canonical pathways overlapping with EC and SC were predicted to be activated in one cell type and inactivated in the other, while no overlap in eDEGs was assigned to them. We also identified 13 EC-eDEGs and five SC-eDEGs enriched networks, in which the SC-eDEGs were able to segregate FA from PT samples. Conclusions: Identical TERT mutations from both SC and ES origins might affect the PTs tumorigenesis. Gene expression differences suggest coordinated molecular processes between these components with determinant differences acquired by SC, able to fully distinguish PTs from FAs lesions.

Avaliação dos dados contidos nas requisições do exame anatomopatológico da mama na cirurgia de troca ou explante de implantes mamários de silicone: análise de 251 casos / Evaluation of the data contained in the requests for the anatomopathological examination of the breast in the surgery of exchange or explantation of silicone breast implants: analysis of 251 cases

Introdução: A descrição do linfoma anaplásico de células T e o recente aumento das cirurgias de explante resultou na elevação do número de exames anatomopatológicos nas cirurgias de retirada de implantes mamários de silicone. O objetivo desta pesquisa é analisar a qualidade e quantidade de dados contidos na requisição do exame histopatológico. Métodos: Foram estudados 251 casos. Os seguintes dados foram analisados: sexo, idade, localização anatômica e espacial, lateralidade, história clínica, sinais e sintomas, quimioterapia e radioterapia prévia, hipótese diagnóstica, cirurgias prévias, tipo e marca do implante, exames de imagem prévios e número e características dos espécimes enviados. Resultados: A idade média foi de 43 anos. A lateralidade não foi mencionada em 16 (0,84%). A localização anatômica foi citada em 15 casos. O tipo de cirurgia foi mencionado por 40 (15,94%). O número de contêineres variou de 1 a 5, com mediana de 2. A cápsula foi enviada em 242 casos, em 161 de forma isolada, tecido mamário em conjunto com cápsula em 27, tecido mamário e cápsula em contêineres diferentes em 54 casos. A história clínica foi incluída em 19,12%, sinais e sintomas em 13,94%, em que a contratura foi o único termo inserido em 64. Em 27 requisições foi citado linfoma. Em 15 pacientes a presença de seroma foi referida e destes nove foram enviados. O tipo e marca do implante não foi citado. Conclusão: Os dados são escassos. Recomenda-se a criação de protocolos na retirada da cápsula e tecido adjacente, incluindo a orientação anatômica e espacial.

Introduction: The description of the Anaplastic Large Cell Lymphoma and the explantation surgery resulted in an increase of histopathological exams in breast implant removing surgery. Methods: 251 pathology requests were studied. The following data from the medical requests were analyzed: gender, age, type of surgery, number of specimens containers sent, laterality, anatomical and spatial location, clinical history, signs and symptoms, previous radiotherapy, previous chemotherapy, diagnostic hypothesis, previous surgeries, and reference to previous breast exams. Results: The mean age was 43 years old. Laterality was not mentioned in 16 requests. The surgery performed was mentioned in 15.94% requests. The number of containers varies from 1 to 5, with a median of 2. The containers include capsules in 242 cases, 161 as isolated capsule, 27 mammary tissue, and capsule in the same specimen, 54 mammary tissues sent in a separate container, anatomical and spatial location was mentioned in 6.33% cases. The detailed clinical data was included in 19.12%, signs and symptoms 13.94%, contracture as the only item mention in 64 of them. In 27 requests, lymphoma evaluation was requested. 15 included seroma and from nine of those, liquid was sent with a request for immunohistochemical and cytology analysis. None of the requests had any data on implant type or brand. Conclusion: The amount of information contained in the medical request forms is minimal. The authors recommend the need for a protocol to standardize the surgical removal of the capsule and the adjacent mammary tissue. Surgical specimens should be spatially oriented.

Physical exercise is effective for neuropsychiatric symptoms in Alzheimer's disease: a systematic review / Exercício físico é efetivo para sintomas neuropsiquiátricos na doença de Alzheimer: uma revisão sistemática

ABSTRACT Background: Neuropsychiatric symptoms are disorders frequently seen in Alzheimer's disease. These symptoms contribute to reduction of brain reserve capacity and, in addition, they present unfavorable implications, such as: poor prognosis for the disease, increased functional decline, increased burden on the caregiver and institutionalization. This scenario makes neuropsychiatric symptoms one of the biggest problems in Alzheimer's disease, and gives rise to a need for treatments focused on improving these symptoms. Sow progress in drug trials has led to interest in exploring non-pharmacological measures for improving the neuropsychiatric symptoms of Alzheimer's disease, such as physical exercise. Objective: To ascertain the effect of exercise on the neuropsychiatric symptoms of Alzheimer's disease and its implications. Methods: This was a systematic review of effective longitudinal research, conducted by searching for articles in the PubMed, Web of Science, CINAHL and Scopus electronic databases, from 2009 to 2019. Studies in which the sample consisted of elderly people aged 65 years old or over with a diagnosis of Alzheimer's disease were included. Initially 334 articles were identified. After exclusions, 21 articles remained to be read in full. From these, five articles fitted the eligibility criteria, and a further two articles were added through manual searches in the references of the articles found. Results: Out of the seven articles analyzed in this review, five studies revealed that physical exercise had a positive effect on the neuropsychiatric symptoms of Alzheimer's disease. Conclusion: This systematic review indicated that physical exercise is a favorable non-pharmacological means for attenuating the neuropsychiatric symptoms of elderly people with Alzheimer's disease, with special attention to aerobic exercises.

RESUMO Introdução: Sintomas neuropsiquiátricos são desordens frequentemente observadas na Doença de Alzheimer, os quais contribuem para a diminuição da capacidade de reserva cerebral e ocasiona implicações ruins, como mau prognóstico da doença, aumento do declínio funcional, aumento da sobrecarga do cuidador e institucionalização. Esse cenário faz com que os sintomas neuropsiquiátricos se tornem um dos maiores problemas da Doença de Alzheimer, incitando, assim, o interesse em explorar medidas não-farmacológicas nos sintomas neuropsiquiátricos na Doença de Alzheimer, como o exercício físico. Objetivo: Verificar o efeito do exercício físico em sintomas neuropsiquiátricos da Doença de Alzheimer e suas implicações. Métodos: Trata-se de uma revisão sistemática com pesquisas longitudinais efetivadas por meio da busca de artigos nas bases de dados eletrônicas: PubMed, Web of Science, CINAHL e Scopus, de 2009 a 2019. Foram incluídos estudos cuja amostra foi constituída por idosos com diagnóstico de Doença de Alzheimer com idade igual ou acima de 65 anos. Inicialmente, foram identificados 334 artigos; após as exclusões, restaram 21 artigos para leitura na íntegra. Destes, cinco artigos se enquadraram nos critérios de elegibilidade, assim como dois artigos adicionados por meio de busca manual nas referências dos artigos encontrados. Resultados: Dos sete artigos analisados na presente revisão, cinco estudos revelaram um efeito positivo do exercício físico em sintomas neuropsiquiátricos na Doença de Alzheimer. Conclusão: Esta revisão sistemática indica que o exercício físico é um meio não-farmacológico favorável à atenuação dos sintomas neuropsiquiátricos de idosos com Doença de Alzheimer, com especial atenção na modalidade aeróbia.

Inpatient flow for Covid-19 in the Brazilian health regions / Fluxo de internação por Covid-19 nas regiões de saúde do Brasil

ABSTRACT The study aims to investigate the flows of Covid-19 hospitalizations in the 450 Brazilian health regions and 117 health macro-regions between March and October 2020. This descriptive study includes all Covid-19 hospitalizations registered in the Influenza Epidemiological Surveillance Information System between the eighth and forty-fourth epidemiological weeks of 2020. In Brazil, 397,830 admissions were identified for Covid-19. Emigration was 11.9% for residents in health regions and 6.8% in macro-regions; this pattern was also maintained during the peak period of Covid-19 hospitalizations. The average evasion for residents of health regions was 17.6% in the Northeast and 8.8% in the South. Evasion was more accentuated in health regions with up to 100 thousand inhabitants(36.9%), which was 7 times greater than that observed in health regions with more than 2 million inhabitants (5.2%). The negative migratory efficacy indicator (-0.39) revealed a predominance of evasion. Of the 450 Brazilian health regions, 117 (39.3%) had a coefficient of migratory efficacy between-1 and-0.75, and 113 (25.1%) between-0.75 and-0.25. Results indicate that the regionalization of the health system exhibited adequate organization of healthcare in the territory; however, the long distances traveled are still worrisome.

RESUMO Objetivou-se investigar os fluxos de internações por Covid-19 nas 450 regiões e 117 macrorregiões de saúde brasileiras, de março a outubro de 2020. Realizou-se estudo descritivo, compreendendo todas as internações por Covid-19 registradas no Sistema de Informação de Vigilância Epidemiológica da Gripe entre a 8ª e a 44ª semanas epidemiológicas de 2020. Identificaram-se 397.830 internações por Covid-19 no Brasil. A evasão foi de 11,9% dos residentes nas regiões de saúde e de 6,8% nas macrorregiões; padrão que se manteve no período de pico das internações por Covid-19. Houve, em média, 17,6% de evasão dos residentes das regiões de saúde do Nordeste e de 8,8% das do Sul. A evasão foi mais acentuada nas regiões de saúde com até 100 mil/hab. (36,9%), a qual foi 7 vezes maior que a verificada naquelas com mais de 2 milhões/habitantes (5,2%). O indicador de eficácia migratória negativo (-0,39) indicou predomínio da evasão. Das 450 regiões de saúde brasileiras, 117 (39,3%) apresentaram coeficiente de eficácia migratória entre-1 e-0,75; e 113 (25,1%), entre-0,75 e-0,25. Os resultados indicam que a regionalização do sistema de saúde mostrou-se adequada na organização do atendimento no território, porém, as longas distâncias percorridas ainda são preocupantes.

Forecast UTI: aplicativo para previsão de leitos de unidades de terapia intensiva no contexto da pandemia de COVID-19 / Forecast UTI: aplicación para prever camas en Unidades de Cuidados Intensivos en el contexto de la pandemia de COVID-19 / Forecast UTI: application for predicting intensive care unit beds in the context of the COVID-19 pandemic

Frente à necessidade de gerenciamento e previsão do número de leitos de unidades de terapia intensiva (UTIs) para pacientes graves de COVID-19, foi desenvolvido o Forecast UTI, um aplicativo de livre acesso, que permite o monitoramento de indicadores hospitalares com base em dados históricos do serviço de saúde e na dinâmica temporal da epidemia por coronavírus. O Forecast UTI também possibilita realizar previsões de curto prazo do número de leitos ocupados pela doença diariamente, e estabelecer possíveis cenários de atendimento. Este artigo apresenta as funções, modo de acesso e exemplos de uso do Forecast UTI, uma ferramenta computacional destinada a auxiliar gestores de hospitais da rede pública e privada do Sistema Único de Saúde (SUS) no subsídio à tomada de decisão, de forma rápida, estratégica e eficiente.

En vista de la necesidad de administrar y prever el número de camas en la Unidad de Cuidados Intensivos para pacientes graves de COVID-19, se desarrolló Forecast UTI: una aplicación de acceso abierto que permite el monitoreo de indicadores hospitalarios basados en datos históricos del servicio salud y la dinámica temporal de esta epidemia por coronavirus También es posible hacer pronósticos a corto plazo del número de camas ocupadas diariamente por la enfermedad y establecer posibles escenarios de atención. Este artículo presenta las funciones, el modo de acceso y ejemplos de uso de Forecast UTI, una herramienta computacional capaz de ayudar a los gestores de hospitales públicos y privados en el Sistema Único de Salud, ya que apoyan la toma de decisiones de manera rápida, estratégica y eficiente.

In view of the need to manage and forecast the number of Intensive Care Unit (ICU) beds for critically ill COVID-19 patients, the Forecast UTI open access application was developed to enable hospital indicator monitoring based on past health data and the temporal dynamics of the Coronavirus epidemic. Forecast UTI also enables short-term forecasts of the number of beds occupied daily by COVID-19 patients and possible care scenarios to be established. This article presents the functions, mode of access and examples of uses of Forecast UTI, a computational tool intended to assist managers of public and private hospitals within the Brazilian National Health System by supporting quick, strategic and efficient decision-making.

Fatores associados ao comportamento da população durante o isolamento social na pandemia de COVID-19 / Factors associated with people's behavior in social isolation during the COVID-19 pandemic

Resumo O artigo apresenta resultados da pesquisa de opinião realizada no Brasil sobre a percepção do isolamento social durante a pandemia de COVID-19. O questionário foi elaborado no Google Forms, disseminado por redes sociais, com questões sobre o perfil socioeconômico e fatores associados ao isolamento. Obteve-se uma amostra com 16.440 respondentes. Os dados foram analisados no software Stata 13. O convívio social foi o aspecto mais afetado entre pessoas com maior escolaridade e renda 45,8%, para pessoas de baixas renda e escolaridade, problemas financeiros provocam maior impacto 35%. Os que praticam atividade física revelaram menores níveis de estresse 13%, bem como uma maior normalidade no sono 50,3%. Pessoas que referiram residir em piores condições de habitabilidade, informaram disposição a permanecer menos tempo isoladas 73,9%. Dentre as pessoas que não estão isoladas (10,7% do total), 75,8% acredita que o isolamento social reduzirá o número de vítimas da COVID-19. Concluímos, que a percepção das pessoas quanto ao isolamento social como medida de mitigação da pandemia, varia conforme a renda, escolaridade, idade e sexo, porém a maior parte acredita que se trata da medida de controle mais indicada e estão dispostas a esperar o tempo que for necessário para contribuir com o enfrentamento à COVID-19.

Abstract This paper presents the results of an opinion poll conducted in Brazil on the perception of social isolation during the COVID-19 pandemic. The questionnaire was prepared on Google Forms, disseminated through social networks, with questions about the socioeconomic profile and factors associated with isolation. A non-probabilistic sample was obtained with 16,440 respondents. Data were analyzed using the Stata 13 software. Social interaction was the most affected aspect among people with higher education and income (45.8%), and financial problems caused a more significant impact (35%) among people with low income and education. Those who practice some physical activity showed lower levels of stress 13%, as well as greater normality in sleep 50.3%. People who reported living in worse habitability conditions reported willingness to remain isolated for less time, 73.9%. Among non-isolated people (10.7% of the total sample), 75.8% believe that social isolation will reduce the number of victims of COVID-19. We conclude, based on this sample, that the perception about social isolation as a pandemic mitigation action varies by income, education, age, and gender. However, most believe that it is the most appropriate control measure and are willing to wait as long as necessary to contribute to the fight against COVID-19.

É o carcinoma colônico localmente avançado não metastático uma variante biológica distinta? Estudo baseado na avaliação histológica, painel imuno-histoquímico e sobrevida / Is the non-metastatic, locally advanced colon adenocarinoma a distinct biological tumor variant? A study based on pathological evaluation, immunohistochemical panel and survival

RESUMO Objetivo: avaliar diferenças clínicas e patológicas entre os adenocarcinomas colônicos localmente avançados com aderências entre órgãos ou estruturas adjacentes (LACA) e adenocarcinomas colônicos com outras apresentações clínicas. Métodos: estudo retrospectivo a partir de amostra de conveniência de pacientes com adenocarcinoma colônico, estádio patológico pT3, distribuídos de acordo com características clínicas e patológicas em três grupos: tumores localmente avançados (LACA), tumores pT3 sem aderências ou metástases à distância (SF), e tumores com doença metastática (M1). Foram avaliadas as características clínicas e patológicas, e a expressão de sete marcadores imuno-histoquímicos relacionados à proliferação/apoptose, invasão celular/migração e metástase. Resultados: foram avaliados 101 pacientes: 30 LACA, 44 SF e 27 M1. Tumores localmente avançados apresentaram dimensões maiores e estiveram associados a aumento das taxas de infiltração linfocitária, menores níveis de expressão de bax e de CD 44v6 quando comparados aos grupos SF e M1. Diferenças significantes foram observadas em relação aos LACA e M1 em relação à localização colônica, histologia, estado linfonodal e expressão bax e CD44v6. Diferenças foram observadas em relação aos três grupos frente ao tamanho do tumor e infiltrado linfocítico. A sobrevida foi similar entre os grupos LACA e SF (p=0,66) e foi inferior no grupo M1 (p<0,001). Conclusão: os dados sugerem que os adenocarcinomas colônicos localmente avançados com aderências entre órgãos ou estruturas adjacentes representam uma entidade distinta.

ABSTRACT Objective: to evaluate the clinical and pathological differences between locally advanced colonic adenocarcinomas (LACA) with adhesions between adjacent organs or structures, and colonic adenocarcinomas with other clinical presentations. Methods: we conducted a retrospective study from a convenience sample of patients with colonic adenocarcinoma, pathological stage pT3, distributed according to clinical and pathological characteristics in three groups: locally advanced tumors (LACA), pT3 tumors without adhesions or distant metastases (SF) and tumors with metastatic disease (M1). We evaluated clinical and pathological characteristics and the expression of seven immunohistochemical markers related to proliferation/apoptosis, cell invasion/migration and metastasis. Results: we studied 101 patients: 30 LACA, 44 SF and 27 M1. Locally advanced tumors presented larger dimensions and were associated with increased lymphocyte infiltration rates, lower levels of bax expression, and CD 44v6 when compared with SF and M1 groups. We observed significant differences between LACA and M1 in relation to colonic location, histology, lymph node status and bax and CD44v6 expression. We found differences were observed between the three groups for tumor size and lymphocytic infiltrate. Survival was similar in the LACA and SF groups (p=0.66) and was lower in the M1 group (p<0.001). Conclusion: the data suggest that locally advanced colonic adenocarcinomas with adhesions between adjacent organs or structures represent a distinct entity.

Characteristics of follicular and mantle cell lymphoma in Brazil: prognostic impact of clinical parameters and treatment conditions in two hospitals

ABSTRACT Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. Conclusion: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.

Diagnostic utility of DREAM gene mRNA levels in thyroid tumours

ABSTRACT Objective The transcriptional repressor DREAM is involved in thyroid-specific gene expression, thyroid enlargement and nodular development, but its clinical utility is still uncertain. In this study we aimed to investigate whether DREAM mRNA levels differ in different thyroid tumors and how this possible difference would allow the use of DREAM gene expression as molecular marker for diagnostic and/or prognosis purpose. Materials and methods We quantified DREAM gene mRNA levels and investigated its mutational status, relating its expression and genetic changes to diagnostic and prognostic features of 200 thyroid tumors, being 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesions [49 goiter and 50 follicular adenomas (FA)]. Results Levels of mRNA of DREAM gene were higher in benign (0.7909 ± 0.6274 AU) than in malignant (0.3373 ± 0.6274 AU) thyroid lesions (p < 0.0001). DREAM gene expression was able to identify malignancy with 66.7% sensitivity, 85.4% specificity, 84.2% positive predictive value (PPV), 68.7% negative predictive value (NPV), and 75.3% accuracy. DREAM mRNA levels were also useful distinguishing the follicular lesions FA and FVPTC with 70.2% sensitivity, 73.5% specificity, 78.5% PPV, 64.1% NPV, and 71.6% accuracy. However, DREAM gene expression was neither associated with clinical features of tumor aggressiveness, nor with recurrence or survival. Six different genetic changes in non-coding regions of DREAM gene were also found, not related to DREAM gene expression or tumor features. Conclusion We suggest that DREAM gene expression may help diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions; however, it is not useful as a prognostic marker.

Assessment of HER-2 status in invasive breast cancer in Brazil / Avaliação de HER-2 no câncer de mama invasivo no Brasil

Summary Objective: To characterize the frequency of HER-2-positive breast cancer in Brazil. Method: In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH). Results: From February, 2011 to December, 2012, 1,495 breast specimens were registered, and 1,310 samples collected at 24 centers were analyzed. Median patient age was 54 years, and the majority of samples were obtained from segmental (46.9%) or radical mastectomy (34.4%). The predominant histological type was invasive breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3), and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0 or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2- -positive by either method). We found no association between HER-2 scores and menopausal status or histological type. Tumors classified as 3+ came from younger patients, and had higher histological grade and less frequent expression of ER/PR. In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in the other four regions of the country. Conclusion: Our findings provide estimates for the frequency of HER-2 positivity in Brazil and raise the hypothesis that biological differences may underlie the different distribution of breast-cancer phenotypes among different Brazilian regions.

Resumo Objetivo: Estimar a frequência de câncer de mama positivo para HER-2 no Brasil. Método: Neste estudo observacional e prospectivo, verificamos o escore de HER-2 de espécimes de câncer de mama invasivo por imuno-histoquímica automatizada (IHQ). Para amostras classificadas como 2+ por IHQ, fizemos hibridização in situ (HIS). Resultados: De fevereiro de 2011 a dezembro de 2012, 1.495 espécimes de mama foram registrados, e 1.310 amostras coletadas por 24 centros foram analisadas. A idade mediana das pacientes foi 54 anos, e a maioria das amostras foram obtidas a partir de mastectomia segmentar (46,9%) ou radical (34,4%). O tipo histológico predominante foi o carcinoma invasivo da mama, sem tipo especial (85%); 64,3% tinham formação de túbulos (grau 3); e os receptores de estrógeno (RE)/progesterona (RP) foram positivos em 77,4%/67,8% das amostras analisadas. Por IHQ, encontramos HER-2 negativo (0 ou 1+) em 72,2% das amostras, e 3+ em 18,5%; os 9,3% de casos classificados como 2+ foram analisados por HIS, e 15,7% deles foram positivos (assim, 20,0% das amostras foram positivas para HER-2 por qualquer método). Não encontramos associação entre escores de HER-2 e estado menopausal ou tipo histológico. Tumores classificados como 3+ vieram de pacientes mais jovens, tinham maior grau histológico e foi menos frequente a expressão de RE/RP. Na região Norte do Brasil, 34,7% das amostras foram 3+, com frequências mais baixas nas outras quatro regiões do país. Conclusão: Nossos resultados permitem estimar a frequência de positividade do HER-2 no Brasil, gerando a hipótese de que pode haver diferenças biológicas subjacentes à distribuição dos fenótipos de câncer de mama entre as diferentes regiões brasileiras.

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed. Methods: We evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors. Results: The Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB. Conclusion: NCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined (AU)

Tumor banking for health research in Brazil and Latin America: time to leave the cradle

Cancer is rapidly growing to be one of the major health burdens in Brazil and Latin America. Access to tumor samples is one of the many barriers that need to be removed in order to promote clinical and translational research aimed at developing and improving cancer prevention and treatment in this region. Although there is a growing interest in establishing tumor collections in many hospitals and institutions, success is limited by the lack of knowledge of the complexities of this activity. This article reviews the regulatory, pathology, and molecular aspects that are relevant to the establishment of tumor banks in Brazil and Latin America. It also provides an overview of key players in the region (AU)

Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases

Oral squamous cell carcinoma (OSCC) is the eighth most prevalent cancer worldwide. In recent large-scale studies, by immunohistochemistry and cluster analysis, several markers were associated with patient survival in various tumors. The aim of this study was to analyze the expression profiles of 23 proteins that have been linked to the inhibition (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1, and survivin) and promotion (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA, Apaf-1, caspase-2, caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, Smac/DIABLO, and cytochrome c) of apoptosis in OSCC. METHODS: Two-hundred and twenty nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analyzed, and the results were quantified on an automated imaging system. The data were analyzed using a random forest clustering method. RESULTS: Overall protein expression patterns defined two chief clusters: an anti-apoptotic cluster (142 cases) and a pro-apoptotic cluster (29 cases). These groups could not be explained by any clinical or pathological characteristic, and overall and disease-free survival did not differ between them. CONCLUSIONS: Although there was no association with survival, the cluster analysis demonstrated specific protein profiles that could be of interest for using targeted therapies: in one of the clusters, the expression of pro-apoptotic proteins was more prominent, demonstrating a pro-apoptotic profile and highlighting the importance of apoptosis during OSCC development.

Inflammatory pseudotumor-like follicular dendritic cell tumor: an underdiagnosed neoplasia

Follicular dendritic cell (FDC) tumor is an uncommon neoplasm. It generally presents as a slow-growing, painless mass, without systemic symptoms. Histological features usually include low grade spindle cell proliferation. This tumor occurs primarily in lymph nodes, especially cervical and axillary, however, involvement of extranodal sites such as the tonsils, spleen, liver, and gastrointestinal tract has been reported. Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) is a rare, distinctive histological subtype of this low-grade malignant neoplasm, with consistent Epstein-Barr virus (EBV) association. The differential diagnosis with other fibro-inflammatory tumor proliferations, as inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT), may be challenging. In the present article, two cases of IPT-like FDCT of the spleen are presented, with a broad overview of the literature: one 77-year-old male and one 70-year-old female. A large immunohistochemical panel should be used for diagnosis, as no single specific and totally sensitive markers are available, including markers for CD21, CD23, CD35, CNA42, and clusterin. Individual cases may express one or more of these markers, so that all of them should be investigated. In situ hybridization for EBV is constantly positive. Immunostaining for ALK should be negative, as it is present in roughly half of the cases of IMT. This panel should be used in combination of clinical, laboratory, and topographic evidences. Importantly, inclusion of this lesion as a possible option in clinical and pathological investigation represents the basis for a correct diagnosis (AU)

Tumor histologic grade is the most important prognostic factor in patients with penile cancer and clinically negative lymph nodes not submitted to regional lymphadenectomy

ABSTRACT Introduction: The presence and extension of inguinal lymph node metastasis are the main prognostic factors in patients with penile cancer. Physical exam and image exams are not adequate to evaluate inguinal lymph nodes and many patients are submitted to non-therapeutic lymphadenectomies. However, it is known that not all patients with clinically or histologically negative inguinal lymph nodes evolve favorably. Casuistic and Methods: the authors evaluated the clinical and pathologic characteristics of 163 patients with penile carcinoma and clinically negative inguinal lymph nodes followed for three or more years and their impact on global survival (GS) and cancer-specific survival (CSS) in the 10-year follow-up. Primary pathologic tumor stage (p=0.025) and the presence of high grade of tumor differentiation (p=0.018) were predictive of CSS. The presence of high grade tumor was an independent specific prognostic factor of death risk (RR 14.08; p=0.019). Conclusion: high histologic grade was an independent predictive factor of specific death risk in patients with penile carcinoma and clinically negative lymph nodes followed for three or more years.

Cytokeratin immunoprofile of primary and metastatic adenoid cystic carcinoma of salivary glands: a report of two cases

Distant metastases from salivary gland tumors are considered infrequent: the incidence of distant metastases ranges from 24% to 61% according to different histotypes and to the site of the primary mass. The most common site of distant metastases due to salivary gland malignancies is the lung. From the pathology point of view, cytokeratins (CK) are important differentiation markers in salivary gland tumors, which are often used for the diagnostic process. Their employment also may be useful to identify and confirm the diagnosis of their distant metastases. We report the expression of CK in two cases of primary and metastatic adenoid cystic carcinoma (ACC) and their CK profiles of the primary and metastatic masses. Both patients-one male and one female-were diagnosed with an ACC cribriform and tubular, respectively, with lung metastases. In case 1, the metastatic mass presented the same histotype and CK profile of the primary tumor. For case 2, the metastatic lung mass was distinct from the primary mass (a solid ACC) and presented a different CK profile. Although salivary gland metastatic disease presents a poor prognosis, both patients reported herein are alive despite the presence of the disease in long-term follow-up. Therefore, the modifications seen in the CK profiles do not appear to be predictive of tumor behavior and outcome. The use of a CK profile seems to be useful to identify the nature of a distant mass and its possible correlations with a primary salivary gland tumor.

Perfil nutricional de pacientes adultos e idosos hospitalizados / Nutritional profile of hospitalized adults and elderly people

O objetivo do estudo foi avaliar os hábitos alimentares em adultos e idosos hospitalizados em um hospital público de Montes Claros (MG). Trata-se de uma pesquisa descritiva, quantitativa e transversal. Foram utilizados, para avaliação nutricional, o Índice de Massa Corporal (IMC) e a Avaliação Subjetiva Global (ASG). A amostra foi composta por 39 pacientes, de ambos os sexos, maiores de 18 anos, selecionados aleatoriamente, internados em um hospital público da cidade de Montes Claros (MG). Verificou-se que 32,35% dos pacientes eram eutróficos, com IMC > 20,5 kg/m², e 61,76% dos pacientes adultos eram obesos, com IMC > 25 kg/m². A desnutrição esteve presente em 5,88% dos pacientes adultos, com IMC < 20,5 kg/m². Com relação aos idosos, foram diagnosticados que 40% destes eram obesos e 20%, desnutridos. Em relação à ASG, adultos e idosos foram classificados na categoria C, gravemente desnutridos. O estado nutricional dos pacientes foi evidenciado pela alta prevalência de risco nutricional e sobrepeso/obesidade. Os resultados presentes evidenciam a importância da utilização de mais de um método de triagem nutricional em pacientes hospitalizados, para obter-se maior precisão na avaliação.

The feeding habits of hospitalized adults and elderly people in a government-run hospital in Montes Claros MG Brazil are evaluated. Current descriptive, quantitative and transversal research comprised nutritional evaluation, Body Mass Index (BMI) and Total Subjective Evaluation (TSE) of 39 patients, males and females, over 18 years old, randomly selected and hospitalized in a government-run hospital in Montes Claros MG Brazil. Further, 32.35% of patients were eutrophic, with BMI > 20.5 kg/m²; 61.76% were obese, with BMI > 25 kg/m². Undernourishment occurred in 5.88% of adult patients, with BMI < 20.5 kg/m². In the case of the elderly, 40% were obese and 20% were undernourished. In the case of TSE, adults and elderly were classified under category C, seriously undernourished. The patients´ nutritional state was proved by high prevalence of nutritional risks and overweight/obesity. Results revealed the importance of the employment of more than one method for nutritional selection in hospitalized patients for better evaluation.

Análise do gene PTEN por hibridização in situ fluorescente no carcinoma de células renais / Analysis of PTEN gene by fluorescent in situ hybridization in renal cell carcinoma

OBJETIVO: avaliar a frequência de deleção do gene PTEN no carcinoma de células renais e o impacto da deleção nas taxas de sobrevida global e livre de doença. MÉTODOS: foram analisados 110 pacientes portadores de carcinoma de células renais submetidos à nefrectomia radical ou parcial entre os anos de 1980 e 2007. Em 53 casos foi possível a análise do gene PTEN pelo método de hibridização in situ fluorescente através da técnica de "tissue microarray". Para a análise estatística, os pacientes foram classificados em dois grupos, de acordo com a presença ou ausência de deleção. RESULTADOS: o tempo médio de seguimento foi de 41,9 meses. Deleção hemizigótica foi identificada em 18 pacientes (33,9%), ao passo que deleção homozigótica esteve presente em três (5,6%). Em aproximadamente 40% dos casos analisados havia deleção. Monossomia e trissomia foram detectadas, respectivamente, em nove (17%) e dois pacientes (3,8%). Em 21 pacientes (39,6%), a análise por hibridização in situ do gene PTEN foi normal. Não houve diferenças estatisticamente significativas nas taxas de sobrevida global (p=0,468) e livre de doença (p=0,344) entre os pacientes portadores ou não de deleção. Foram fatores independentes para a sobrevida global: estádio clínico TNM, sintomatologia ao diagnóstico, alto grau de Fuhrmann performance status (Ecog) e recorrência tumoral. A livre de doença foi influenciada unicamente pelo estádio clínico TNM. CONCLUSÃO: deleção do gene PTEN no CCR foi detectada com frequência de aproximadamente 40% e sua presença não foi determinante de menores taxas de sobrevida, permanecendo os fatores prognósticos tradicionais como determinantes da evolução dos pacientes.

OBJECTIVE: To evaluate the frequency of deletion of the PTEN gene in renal cell carcinoma (RCC) and its impact on the rates of overall and disease-free survival. METHODS: We analyzed 110 patients with renal cell carcinoma who underwent radical or partial nephrectomy between 1980 and 2007. In 53 cases it was possible to analyse the PTEN gene by the method of fluorescent in situ hybridization using the technique of tissue microarray. For statistical analysis, patients were classified in two groups according to the presence or absence of the deletion. RESULTS: The mean follow-up time was 41.9 months. Hemizygous deletion was detected in 18 patients (33.9%), while the homozygous one was present in three (5.6%). Deletion was present in approximately 40% of the analyzed cases. Monosomy and trisomy were detected in nine (17%) and two patients (3.8%), respectively. In 21 patients (39.6%) the analysis of the PTEN gene by in situ hybridization was normal. There were no statistically significant differences in overall (p = 0.468) and disease-free (p = 0.344) survival rates between patients with or without deletion. Factors which were independent for overall survival: TNM clinical stage, symptoms at diagnosis, high Fuhrmann grade, performance status (ECoG) and tumor recurrence. Disease-free survival was influenced only by the clinical TNM stage. CONCLUSION: Deletion of the PTEN gene in RCC was detected with a frequency of approximately 40% and its presence was not determinant of lower survival rates, the traditional prognostic factors remaining as determinants of outcome.

Human Papilloma Virus: Prevalence, distribution and predictive value to lymphatic metastasis in penile carcinoma

Objectives To evaluate the prevalence, distribution and association of HPV with histological pattern of worse prognosis of penile cancer, in order to evaluate its predictive value of inguinal metastasis, as well as evaluation of other previous reported prognostic factors. Material and Methods Tumor samples of 82 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR. HPV status was correlated to histopathological factors and the presence of inguinal mestastasis. The influence of several histological characteristics was also correlated to inguinal disease-free survival. Results Follow-up varied from 1 to 71 months (median 22 months). HPV DNA was identified in 60.9% of sample, with higher prevalence of types 11 and 6 (64% and 32%, respectively). There was no significant correlation of the histological characteristics of worse prognosis of penile cancer with HPV status. Inguinal disease-free survival in 5 years did also not show HPV status influence (p = 0.45). The only independent pathologic factors of inguinal metastasis were: stage T ≥ T1b-T4 (p = 0.02), lymphovascular invasion (p = 0.04) and infiltrative invasion (p = 0.03). conclusions HPV status and distribution had shown no correlation with worse prognosis of histological aspects, or predictive value for lymphatic metastasis in penile carcinoma. .

Survival in patients with oral and maxillofacial diffuse large B-cell lymphoma

The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A) overall survival (OS) at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables), and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor); (B) prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox), and multivariate analysis with Cox's regression model (all the variables together). The data were considered significant at p ≤ 0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3%) occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p = 0.042), clinical stage (p = 0.007) and performance status (p = 0.031). These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status.