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INTRODUCTION: According to the cancer stem-cell theory, tumors originate from a small population of cancer stem cells, which lose the mechanism of self-regulation and begin to differentiate and proliferate indefinitely. The CD44+/CD24- phenotype may be considered a stem-cell marker in breast cancer. OBJECTIVE: To evaluate the correlation between CD44+/CD24- phenotype and different molecular subtypes of breast cancer in invasive ductal carcinoma samples. METHODS: The expression of CD44, CD44v6, and CD24 markers was investigated in 133 cases of invasive mammary carcinoma with immunohistochemistry. CD44+/CD24- phenotype was identified and correlated with the molecular subtypes and classical prognostic factors such as age, histological grade, tumor size, and lymph node status. RESULTS: Eighteen (14%) cases were positive for CD44+/CD24- (CD44+/CD24- or CD44v6+/CD24-) phenotype; among these, 11.1%, 27.8%, 38.9%, and 22.2% were luminal, luminal B-human epidermal growth factor receptor 2 (HER2), HER2, and triple-negative subtype, respectively. CD44+/ CD24- phenotype was more common in HER2 subgroup (p = 0.0197). CONCLUSION: CD44+/CD24- phenotype was correlated with molecular subtypes of breast cancer. The highest expression of CD44+/CD24- phenotype was reported in patients with HER2+ disease, a molecular subtype associated with more aggressive behavior and worse prognosis. RESUMO INTRODUÇÃO: De acordo com a teoria das células-tronco tumorais, os tumores são originários de uma pequena população de células-tronco que perdem o mecanismo de autorregulação e começam a se diferenciar e proliferar indefinidamente. O fenótipo CD44+/CD24- pode ser considerado um marcador de células-tronco tumorais no câncer de mama. OBJETIVO: Avaliar a correlação entre o fenótipo CD44+/CD24- e os diferentes subtipos moleculares do câncer de mama em amostras de carcinoma ductal invasor. MÉTODOS: A expressão dos marcadores CD44, CD44v6 e CD24 foi investigada em 133 casos de carcinoma mamário invasor por meio de imuno-histoquímica. O fenótipo CD44+/CD24- foi identificado e correlacionado com os subtipos moleculares e os fatores prognósticos clássicos, como idade, grau histológico, tamanho do tumor e status do linfonodo. RESULTADOS: Dezoito (14%) casos foram positivos para o fenótipo CD44+/CD24- (CD44+/CD24- ou CD44v6+/CD24-), sendo 11, 1%, 27, 8%, 38, 9% e 22, 2% dos subtipos luminal, luminal B-human epidermal growth factor receptor 2 (HER2), HER2 e triplo negativo, respectivamente. O fenótipo CD44+/CD24- foi mais comum no subgrupo HER2 (p = 0, 0197). CONCLUSÃO: O fenótipo CD44+/CD24- foi correlacionado com os subtipos moleculares do câncer de mama. A maior expressão do fenótipo CD44+/CD24- foi encontrada em pacientes com doença HER2+, subtipo molecular associado a um comportamento mais agressivo e a um pior prognóstico.

This study aimed to evaluate the new immunohistochemical markers related to neuroendocrine differentiation induction and stem cells with prognostic factors and biochemical recurrence in patients submitted to radical prostatectomy. Therefore, patients operated at the Hospital Walter Cantídio, Federal University of Ceará, in the period of 2008-2013, underwent clinical and outpatient follow-up, between the years 2008-2016. Biochemical recurrence was evaluated and was correlated with pathological characteristics and immunohistochemical reactions. Chromogranin (neuroendocrine differentiation), Aurora Kinase A (AURKA), N-MYC, C-MYC and CD44s were performad in paraffined material. From 74 patients underwent surgery was obtained the followup of 69, in a median period of 41 (2-89) months. Neoplastic neuroendocrine differentiation was associated with seminal vesicles infiltration (p = 0.032) and stage (p = 0.030). C-MYC was associated with Gleason score (p = 0.001) and seminal vesicles infiltration (p = 0.014). AURKA was expressed in rare cases. N-MYC protein was negative in all patients. CD44s was associated with lower preoperative PSA levels and lower Gleason scores. Biochemical recurrence was observed in 27.0% of patients. Recurrence was associated with serum preoperative PSA, Gleason score, seminal vesicle invasion and staging at least in one form of analysis. There was no significant association between recurrence and neuroendocrine differentiation, C-MYC and CD44s expression. Therefore, immunohistochemical detection of neuroendocrine differentiation, expression of C-MYC and loss of CD44s were related to more aggressive carcinomas (PSA, Gleason, seminal vesical invasion and/or stage), but no association with biochemical recurrence. Classic prognostic factors were affirmed like biochemical recurrence predictores. Este estudo objetivou avaliar novos marcadores imuno-histoquímicos relacionados à indução da diferenciação neuroendócrina e células-tronco com fatores de prognóstico e recorrência bioquímica, em pacientes submetidos à prostatectomia radical. Para tanto, pacientes operados no Hospital Walter Cantídio, Universidade Federal do Ceará, no período de 2008 a 2013, foram submetidos a acompanhamento clínico-ambulatorial, entre os anos de 2008 a 2016. Avaliou-se a proporção daqueles que apresentaram recorrência bioquímica, bem como as características clínico-patológicas e a marcação em reações de imuno-histoquímica para cromogranina (diferenciação neuroendócrina), Aurora quinase A (AURKA), N-MYC, C-MYC e CD44s, em material parafinado. De 74 pacientes submetidos à cirurgia, obteve-se acompanhamento de 69, com tempo de seguimento de 41 (2-89) meses; diferenciação neuroendócrina na neoplasia se associou com infiltração de vesículas seminais (p=0,032) e estadiamento (p=0,030). C-MYC associou-se com escore de Gleason (p=0,001) e infiltração de vesículas seminais (p=0,014). AURKA expressou-se em raros casos. N-MYC foi negativo em todos os pacientes. CD44s se associou com menores níveis de PSA pré-operatório e menores escores de Gleason. Observou-se recorrência bioquímica em 27,0% dos pacientes. Recorrência se associou, em pelo menos uma das formas de análise, com níveis séricos de PSA pré-operatório, escore de Gleason, invasão de vesículas seminais e estadiamento. Não houve associação significativa entre recorrência e diferenciação neuroendócrina, C-MYC e CD44s. Dessa forma, nesse estudo, a detecção imuno-histoquímica da diferenciação neuroendócrina; a expressão de C-MYC e a perda da expressão de CD44s relacionaram-se com carcinomas mais agressivos (PSA, Gleason, infiltração de vesícula seminal e/ou estadiamento), porém sem associação com a recorrência bioquímica; bem como confirma a importância de fatores prognósticos considerados como clássicos em série regional de pacientes com câncer de próstata.

OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and CD44 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA) and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3%) and 60 (67%) of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60%) cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50%) and 82 (74.50%) cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50%) and 48 (42.60%) of the cases, respectively; all of them were highly correlated (pOBJETIVO: O objetivo desse estudo é verificar as expressões e correlações da aromatase, metalloproteinase 2 da matriz (MMP2), metalloproteinase 9 da matriz (MMP-9) e CD44 no carcinoma ductal in situ (CDIS) e carcinoma ductal infiltrativo (CDI) quando ambos estão presentes simultaneamente na mesma mama. MÉTODOS: Foram avaliados 110 casos pelo método de tissue microarray (TMA) e através da utilização de anticorpos policlonais antiaromatase, anticorpos monoclonais anti-MMP-2, anticorpos policlonais anti-MMP-9 e anticorpos monoclonais anti-CD44. RESULTADOS: A aromatase estava expressa de forma positiva no CDI e CDIS em 63 (57,3%) e 60 (67%) casos, respectivamente. A expressão de MMP-2 estava expressa de forma positiva em 15 (13,6%) casos tanto no CDI, quanto no CDIS. A expressão da MMP-9 estava expressa de forma positiva em 83 (75,5%) e 82 (74,5%) casos de CDI e CDIS, respectivamente. A expressão de CD44 estava expressa de forma positiva em 49 (44,5%) e 48 (42,6%) casos de CDI e CDIS, respectivamente. Todos eles apresentando alta correlação (p

Gastric cancer is the fourth most common cancer worldwide, accounting for the second leading cause of cancer mortality. Despite treatment with surgery and chemotherapy, the overall five-year survival of patients with gastric cancer remains low. One possible explanation for the ineffectiveness of therapy is the presence of cancer stem cells, a subpopulation of tumor cells that have stem cell characteristics. It has been reported that these, as well as embryonic stem cells, are immortal, can self-renew and to differentiate to be transformed in any cell type in the body. Several markers, including CD44 and CD133, have been reported as stem cell markers in both normal and cancerous cells and have been used to isolate cancer cells from solid tumors. The aim of this study was to evaluate the expression of CD44 and CD133 in primary gastric cancer and lymph node metastases by immunohistochemical and to relate it to clinicopathologic variables as histological type, gender, age, anatomical site, tumor size, angiolymphatic invasion, infiltration perineural, TNM classification (TN) and lymph node involvement. This study was developed from a set of 72 cases of gastric adenocarcinoma, from the Archives of Pathology and Forensic Medicine of the Federal University of Ceará Service (DPML-UFC). Tissue microarray and immunohistochemistry were utilized, with anti-CD44 monoclonal antibody and polyclonal anti-CD133. The cases with one or more cells with cytoplasmic and / or membrane immunostaining were considered positives. It was observed that 30% of the samples were positive for CD44. No statistically significant differences were found between the clinical and pathological variables studied and the immunoreactivity of CD44. Regarding the immunoreactivity of CD133, the present study showed that 24% of samples were positive. The degree of tumor invasion presented data showing a statistically significant trend (p = 0.0505), in reverse. The other variables, we found no statistically significant difference. The immunoreactivity of CD133 in histologically normal mucosa was higher than in the primary tumor and intestinal metaplasia, with statistically significant difference (p = 0.0159 and p = 0.0058, respectively). The CD133 immunostaining in intestinal type gastric carcinoma was significantly higher than in the histologically normal mucosal metaplasia (p = 0.0260). The frequency of expression of these markers is highly variable, and even in the samples considered positive, the stained cells percentage is also variable, and very low overall. O câncer gástrico é a quarta neoplasia mais comum em todo o mundo, representando a segunda causa de mortalidade por câncer. Apesar do tratamento com cirurgia e quimioterapia, a sobrevida global em cinco anos de pacientes com câncer gástrico permanece baixa. Uma possível explicação para ineficácia da terapia é a presença de células-tronco cancerosas, uma subpopulação de células tumorais que apresentam características de células-tronco. Estas células, assim como as células tronco embrionárias, são consideradas imortais, podem se auto-renovar e se transformar em qualquer célula do corpo. Vários marcadores, incluindo CD44 e CD133, têm sido relatados como marcadores de células-tronco, normais e cancerosas, e utilizados para isolar células cancerosas de tumores sólidos. O objetivo desse trabalho foi avaliar a expressão de CD44 e de CD133, no câncer gástrico primário e metástases linfonodais, através de imunohistoquímica, e relacioná-la com as variáveis clínico-patológicas de tipo histológico, sexo, idade, localização anatômica, dimensão do tumor, invasão angiolinfática, infiltração perineural, classificação TNM (TN) e acometimento linfonodal. Este estudo foi desenvolvido a partir de um conjunto de 72 casos de adenocarcinoma gástrico, dos Arquivos do Serviço de Patologia e Medicina Legal da Universidade Federal do Ceará (DPML-UFC). Utilizou-se a técnica de tissue microarray asociada à imunohistoquímica com anticorpo monoclonal anti-CD44 e policlonal anti-CD133. Foram considerados positivos os casos que apresentaram uma ou mais células com imunomarcação citoplasmática e/ou membranar. Foi observado que 30% das amostras foram positivas para o CD44. Não foram encontradas diferenças estatisticamente significantes entre as variáveis clínico-patológicas estudadas e a imunoexpressão de CD44. A imunoexpressão do CD133 foi positiva em 24% das amostras. O grau de invasão do tumor apresentou dados com tendência estatisticamente significante (p=0,0505), de forma inversa. Nas demais variáveis, não foi encontrada nenhuma diferença estatisticamente significante. A imunoexpressão de CD133 na mucosa histologicamente normal foi maior do que no tumor primário e na metaplasia intestinal, com diferença estatística significante (p=0,0159 e p=0,0058, respectivamente). A imunoexpressão de CD133 no adenocarcinoma gástrico tipo intestinal foi significativamente maior na mucosa histologicamente normal do que na metaplasia (p=0,0260). A frequência da expressão desses marcadores é muito variável, e mesmo nas amostras consideradas positivas, o percentual de células coradas também é variável, e em geral muito baixo.

Made available in DSpace on 2014-06-11T19:23:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-23Bitstream added on 2014-06-13T19:29:09Z : No. of bitstreams: 1 gouveia_gm_me_araca.pdf: 550439 bytes, checksum: 076629ee6a296748de89f110784f058d (MD5) Os tumores mamários são as mais freqüentes neoplasias em cadelas, representando cerca de 50% dos tumores diagnosticadas nesta espécie e tem maior incidência em fêmeas de meia idade a idosas. Têm sido utilizadas como modelo de estudo para neoplasias mamárias de mulher devido às várias características comuns como as similaridades histológicas e imuno- histoquímicas. Na última década, estudos baseados nos perfis moleculares das neoplasias mamárias, tornaram possível a identificação de algumas células neoplásicas com características de células tronco – as células tronco tumorais (CTT). Uma das moléculas putativas para marcação das CTTs é o CD44. A telomerase, que vem sendo relatada como marcador tumoral, é potencialmente expressa também em CTTs. Estudos recentes estabeleceram um elo crucial entre a transição epitelial-mesenquimal (EMT) e a aquisição de propriedades moleculares e funcionais de células-tronco. Por este motivo analisamos a expressão das proteínas CD44, Citoqueratinas AE1/AE3 e Vimentina, e da enzima telomerase, em tumores mamários de cadelas a fim de investigar o potencial de marcação de CTTs e sua relação com a EMT. Para tal foram utilizados métodos de imuno-histoquímica em tecidos parafinizados tanto in vivo quanto in vitro, fazendo-se uso de técnicas como Tissue MicroArrays (TMA), citoinclusão de tecidos tumorais e cultivos celulares. A expressão da telomerase nas células de tumores mamários cultivadas foi analizada por PCR em tempo real. Nas amostras de tecido parafinizado in vivo, a imunomarcação da citoqueratina demonstrou diferença significativa entre tumores benignos e malignos (p˂0,05), mostrando-se mais intensa em tumores malignos. Já a vimentina apresentou maior intensidade de marcação em tumores benignos, porém não apresentando diferença significativa (p˂0,05)... Mammary tumors are the most frequent cancers in dogs, representing about 50% of tumors, and have a higher incidence in females of middle aged and elderly. These tumors have been used as a model for breast cancer in women due to several common characteristics such as histological and immunohistochemical similarities. In the last decade, studies based on molecular profiles of breast cancer, made possible the identification of some neoplastic cells with characteristics of stem cells – cancer stem cells (CSC). One of the putative molecules of CSCs is CD44. Telomerase, which has been reported as a tumor marker, is potentially also expressed in CSCs. Recent studies have established a crucial link between the epithelial- mesenchymal transition (EMT) and the acquisition of molecular and functional properties of stem cells. For that reason we analyzed the expression of proteins CD44, Cytokeratins AE1/AE3 and Vimentin, and the telomerase enzyme, in dogs mammary tumors, to investigate the potencial for CSC markers, and its relation with the EMT using immunohistochemistry in paraffin embedded tissues in both in vivo and in vitro, making use of techniques such as Tissue MicroArrays (TMA), cell blocks from tumors and cell cultures. Besides that, we analyzed the telomerase expression in mammary tumor cultivated cells by quantitative real time PCR. Immunostaining of cytokeratin had no significant difference between benign and malignant tumors (p ˂ 0,05), being more intense in malignant tumors. However vimentina showed higher staining intensity in benign tumors, but with no significant difference (p ˂ 0,05). The expression of CD44 was higher in malignant tumors that have greater proliferative and metastatic potencial, however its relation with EMT was not detected in the analyzed tumors. Telomerase expression was positive in the neoplastic cultivated cells, however without significant difference... (Complete abstract click electronic access below)

OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and CD44 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA) and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3%) and 60 (67%) of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60%) cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50%) and 82 (74.50%) cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50%) and 48 (42.60%) of the cases, respectively; all of them were highly correlated (p

Introduction – Altered expression or function of adhesion molecules on leukemic blasts may contribute to the evolution of acute leukemia and its biological behavior. The elevated expression of adhesion molecules in ALL might be correlated with the extramedullary dissemination of blast cells, CNS involvement and leukemia tumor burden. Purpose – To analyze the expression of L-selectin and CD44 in ALL in children and adolescents. As well as to evaluate the prognostic factors (age, gender, initial leukocyte count, immunophenotype, FAB and EGIL classification, DNA index and early response to treatment) and the extramedullary presentation of ALL, to finally correlate the prognostic factors with these adhesion molecules. Patients and Methods – From November 2007 to November 2008, 76 patients with newly diagnosed ALL started on Brazilian GBTLI-ALL Protocol. The diagnosis was based on cytological, immunophenotypic, and cytogenetic methods. The mean fluorescence intensity (MFI) and the percentage of the adhesion molecules blasts cells was measured by flow cytometry using triple staining with McAb directly conjugated. CD45-PerCP positive cells were gated for blasts analysis. Anti-CD44-PE (Clone HP2/9 - Immunostep®) and CD62L-FITC (Clone HI62L - Immunostep®) were used to mark the adhesion molecules. The Cell Quest program was used for data acquisition and analysis. Statistical analysis was done by SPSS 16.0 Software. The association of features, prognosis and response to treatment was assessed by Chi-square, Fisher exact and Mann-Whitney tests. Overall survival curves were constructed by the Kaplan-Meier method and the log-rank test. Multivariate Cox regression analysis showed independent prognostic factors. Results – The mean age at diagnosis was 6.3±0.5 years (range 9mo to 17yr) and 65% of them were boys. Clinical findings were hepatomegaly (63%), splenomegaly (58%), lymphadenopathy (44%). CNS involvement was detected in 6.6% of cases and mediastinal mass appeared in 11.8% of them. Patients were classified into low risk (54%) and high risk (46%). FAB classification identified 83% as L1 and 17% as L2. Immunophenotypically, 89.5% of patients were classified as B-lineage ALL and 10.5% as T-lineage ALL. The most frequent EGIL subtype was B common and pre-B-ALL (51.5% and 45.5%, respectively). DNA index greater than 1.16 was found in 19% of the patients and was associated with favorable prognosis. On the D8 evaluation, 95% of the patients had blast count lower than 1.000/mm3 and leukocyte count lower than 5.000/mm3. The remission induction rate was 95% and there was a rate of 2.6% of death during induction therapy. CD44 had greater expression to the rate of 87.5% in T-cell ALL (MFI=150.44±20.29) with no statistical correlation. A significant positive correlation was demonstrated between 84% of CD44 expression and Leukemia burden tumor cases (p=0.01; OR=4.8). There was statistical correlation between L-selectin expression (87.5%/MFI=272.33±52.72) and T-cell ALL (p=0,004). No significant correlation was detected between L-selectin and CD44 expression and other prognostic factors. Multivariate statistical analysis (adjusted for overall survival) indicated that initial leukocyte count, gender, T immunophenotype and L-selectin were independent factors. Conclusion – L-selectin and CD44 expressions were elevated in ALL studied, mainly in T-cell ALL. The research demonstrated that there is an association between CD44 expression and leukemia tumor burden, which might be involved in the dissemination of leukemic cells and the progression of the disease. Introdução – Alterações na expressão ou função das moléculas de adesão (MA) nas células leucêmicas podem contribuir para a evolução e no comportamento biológico das leucemias agudas. A expressão aumentada nas LLAs parece relacionar-se aos mecanismos de disseminação extramedular dos linfoblastos, infiltração do SNC e formação de massas tumorais. Objetivos – Analisar a expressão da L-selectina e do CD44 nas LLAs em crianças e adolescentes. Avaliar os fatores prognósticos (idade, sexo, leucometria ao diagnóstico, imunofenótipo, classificação FAB, EGIL, índice de DNA e resposta ao tratamento de indução) e as apresentações extramedulares das LLAs e correlacioná-los com essas MA. Pacientes e Métodos – Foram avaliados 76 pacientes com LLA, tratados com o Protocolo GBTLI-LLA. O diagnóstico foi baseado em critérios FAB, imunofenotípicos (EGIL) e citogenéticos. A expressão das MA foi avaliada por citometria de fluxo, utilizando tripla marcação. O anticorpo monoclonal CD45-PerCP (Immunotech®) foi utlizado como marcador dos linfoblastos. O CD44-PE (Clone HP2/9 - Immunostep®) e o CD62L-FITC (Clone HI62L - Immunostep®) foram utilizados para a marcação das MA. Para a análise das amostras e o cálculo da intensidade média de fluorescência foi utilizado o programa Cell Quest. Na análise estatística utilizou-se o software SPSS 16.0. A associação entre as variáveis, os fatores prognósticos e resposta foi realizada com os testes de Qui-quadrado, exato de Fisher e Mann-Whitney. Sobrevida global foi determinada por curvas Kaplan-Meier e teste log-rank. Análise multivariada por modelo proporcional de Cox foi utilizada para assegurar a independência dos fatores prognósticos. Resultados – A média de idade foi 6,3±0,5 anos (5m -17a) e predominou o sexo masculino (65%). Ao diagnóstico os achados clínicos foram: hepatomegalia (63%), esplenomegalia (58%) e linfadenomegalia (44%). A infiltração SNC ocorreu em 6,6% dos casos e o alargamento de mediastino em 11,8%. Quanto ao risco, 54% eram baixo risco e 46% alto risco. A classificação FAB determinou 83% como L1 e 17% L2. Diagnóstico de LLA-B foi mais frequente (89,5%) e o da LLA-T em 10,5% dos pacientes. O subtipo EGIL mais prevalente foi B II e B III, 51,5% e 45% respectivamente. O IDNA ≥ 1.16 foi encontrado em 19% dos pacientes e associou-se a bom prognóstico. Na avaliação do D8, 95% dos pacientes apresentaram contagem de blastos