The canonical wnt pathway in gastric carcinoma / Via canônica do wnt no carcinoma gástrico

ABSTRACT Background : It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. Aim : To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. Method : The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. Results : There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. Conclusion: The canonical WNT pathway is involved in gastric carcinoma.

RESUMO Racional : Acredita-se que a via Wnt é uma das mais importantes da sinalização envolvidas na carcinogênese gástrica. Objetivos : Analisar a expressão das proteínas das vias Wnt canônicas e não-canônicas no carcinoma gástrico e relacionar sua expressão com as variáveisclinicopatológicas. Método : Foram coletadas 72 amostras de carcinoma gástrico, e áreas representativas do tumor foram selecionadas para o Tissue Microarray. Imunoistoquímica foi realizada para avaliar a expressão de Wnt-5a, FZD5, GSK3β, axina, CK1, ubiquitina, ciclina D1 e c-myc. Resultados : Houve diferenças significativas para a expressão de ubiquitina no citoplasma e núcleo para tumores moderadamente e bem diferenciados (p=0,03) e para aqueles do tipo intestinal da classificação de Lauren (p=0,03). A expressão negativa da proteína c-myc no citoplasma foi relacionada aos tumores intestinais de Lauren (p=0,028). A expressão positiva de CK1 no citoplasma das células neoplásicas foi relacionada a tumores com margens cirúrgicas livre de envolvimento neoplásico (p=0,03). A expressão positiva da proteína ciclina D1 foi maior nos tumores dos homens (p=0,03). Não houve relação da expressão positiva ou negativa das proteínas Wnt-5a e FZD5 no citoplasma ou núcleo com quaisquer variáveis clinicopatológicas. O mesmo foi observado para GSK3β e Axin. Conclusões : A relação da expressão das proteínas da via canônica com as variáveis epidemiológicas e tumorais sugere sua participação na carcinogênese gástrica. Por outro lado, a ausência da relação das expressões das proteínas da via não-canônica sugere sua não participação na carcinogênese gástrica.

Análise comparativa entre a coloração do azul de toluidina e a imunoexpressão da ciclina D1 em leucoplasias da mucosa bucal com diferentes graus de atipia / Comparative analysis between the coloring of toluidine blue and the immunoexpression of cyclin D1 in leucoplakias of the bucal mucosa with different degrees of atipia

O câncer de boca ocupa uma posição de destaque em relação ao número total de casos registrados no Brasil. A displasia epitelial (DE) oral é um achado histopatológico associado a um risco aumentado de transformação maligna do epitélio oral. A falha nos mecanismos de sinalização celular, no controle do ciclo celular ou nos mecanismos para reparar danos celulares pode favorecer a processos que culminam com a progressão para o câncer. Objetivo: avaliar comparativamente a resposta clínica da marcação do azul de toluidina (AT) e a imunoexpressão da proteína ciclina D1, uma proteína nuclear de grande importância como regulador da transição da fase G1 para fase S do ciclo celular, em leucoplasias oral (LO). Metodologia: avaliamos 12 pacientes que apresentavam, na cavidade bucal, lesões com diagnóstico clínico de LO. O estudo se desenvolveu em duas etapas: clínica e laboratorial. Foi feita marcação com AT e avaliação Imuno-histoquímica, respectivamente. Após análise quantitativa das lâminas, os dados obtidos foram analisados pelo programa BIOESTAT 2.0, por meio dos testes de Spearman e pelo teste de correlações múltiplas de Pearson. Resultados: não foi observada relação entre a marcação clínica do AT, o grau de displasia da lesão e a imunoexpressão da Ciclina D1 em LO. Conclusão: 82% das lesões apresentaram DE em graus variados, confirmando a necessidade de se realizar o diagnóstico histopatológico das LO e o acompanhamento clínico posterior dos pacientes.

Mouth cancer occupies a prominent position in relation to the total number of cases registered in Brazil. Oral epithelial dysplasia (ED) is a histopathological finding associated with an increased risk of malignant transformation of oral epithelium. The failure in the mechanisms of cell signaling, cell cycle control mechanisms or to repair cell damage can favor processes that culminate with the progression to cancer. Objective: evaluate comparatively the clinical response of the toluidine blue marking (TB) and immuno-expression of cyclin D1 protein, a nuclear protein of great importance as a factor regulating the transition from G1 phase to S phase of the cell cycle, in oral leukoplakia (OL). Methodology: we evaluated 12 patients who presented lesions in the oral cavity with clinical diagnosis of OL. The study was developed in two stages: Clinical and Laboratorial. Marking was made with TB and immunohistochemical evaluation, respectively. After quantitative analysis of blades, the data obtained were analyzed by BIOESTAT program 2.0 through Spearman tests and by Pearson multiple correlation test. Results: no relation was observed between clinical marking of TB, the degree of dysplasia of the lesion and the immuno-expression of Cyclin D1 in OL. Conclusion: 82% of the lesions presented DE in varying degrees, confirming the need to perform histopathological diagnosis of the OL and the subsequent clinical monitoring of the patients.

Shenhua Tablet inhibits mesangial cell proliferation in rats with chronic anti-Thy-1 nephritis

BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.

Avaliação da expressão de ß-catenina e ciclina D1 como biomarcadores preditivos para o câncer de lábio / Evaluation of ß-catenin and cyclin D1 expression as predictive biomarkers for lip cancer

Um dos objetivos da pesquisa científica, atualmente, é encontrar biomarcadores que possam auxiliar na definição da probabilidade de progressão das lesões orais displásicas, e ainda sejam capazes de identificar os principais agentes moleculares envolvidos na carcinogênese de um determinado tipo de tumor. Assim, o objetivo deste estudo foi investigar a expressão de ß-catenina, ciclina D1 e Ki-67 em 15 espécimes de epitélio oral normal, 45 queilites actínicas displásicas e em 30 carcinomas espinocelulares de lábio. Essa amostra foi constituída por pacientes tratados na Faculdade de Medicina de Botucatu (Brasil) e no Hospital Clínico San Cecílio de Granada (Espanha). O grau de displasia epitelial e de diferenciação tumoral foi classificado com base nos critérios definidos pela Organização Mundial da Saúde. A avaliação dos biomarcadores foi realizada por meio da técnica imunohistoquímica, dividindo a espessura do epitélio em quatro compartimentos (basal, suprabasal, terço médio e terço superior) para o grupo controle e para as queilites actínicas e em três compartimentos (basal, suprabasal e região interna) para o grupo dos carcinomas espinocelulares de lábio. Para a comparação da média de expressão de cada marcador, nas diferentes localizações do epitélio foi utilizado o teste estatístico de Kruskal-Wallis. Para a correlação da expressão dos três marcadores entre os grupos foi utilizada a correlação de Spearman, com nível de significância de 5%. Os resultados demonstraram uma perda discreta da expressão membranosa de ß-catenina na camada basal das queilites actínicas com displasia epitelial intensa (Cis) e nos carcinomas espinocelulares de lábio, assim como uma expressão citoplasmática e nuclear, discreta e diretamente proporcional à desorganização epitelial nas camadas basal e suprabasal das queilites actínicas e carcinomas espinocelulares de lábio. Notou-se também um aumento da expressão de ciclina D1 e Ki-67 na camada basal à medida que aumentava a desorganização epitelial. Houve uma associação estatisticamente significativa da expressão de ciclina D1 e Ki-67 na camada suprabasal do grupo controle (p=0,030) e das queilites actínicas (p=0,001) e ainda na região interna dos carcinomas espinocelulares de lábio (p=0,000). Não houve correlação significativa entre as expressões nucleares de ß-catenina e de ciclina D1. Nossos resultados reforçam que a ß-catenina, a ciclina D1 e o Ki-67, podem ser utilizados como biomarcadores preditivos para o câncer de lábio. Além disso, sugerem que a ß-catenina e a ciclina D1 participam da carcinogênese labial, em eventos independentes da via de sinalização/Wnt.(AU)

One of the goals of scientific research today is to find predictive biomarkers that can help define the probability of progression of dysplastic oral lesions, and are still able to identify key molecular agents involved in the carcinogenesis of a particular type of tumor. The objective of this study was to investigate ß-catenin, cyclin D1 and Ki-67 expression in 15 specimens of normal oral epithelium, 45 dysplastic actinic cheilitis and 30 squamous cell carcinoma of the lip. This sample consisted of patients treated at the Botucatu Medicine School (Brazil) and the Clinical Hospital San Cecilio of Granada (Spain). The degree of epithelial dysplasia and tumor differentiation was classified based on the criteria defined by the World Health Organization. The evaluation of biomarkers was performed by immunohistochemical technique, dividing the thickness of the epithelium into four compartments (basal, suprabasal, middle third and upper third) for the control group and actinic cheilitis and three compartments (basal, suprabasal and inner region) to the group of squamous cell carcinoma of the lip. For comparing the average expression of each marker in different locations of the epithelium we used the statistical test of Kruskal-Wallis. For the correlation of the three markers expression between the groups was used Spearman, with 5% significance level. The results showed a slight loss of membranous expression of ß-catenin in the basal layer of actinic cheilitis with severe epithelial dysplasia (Cis) and squamous cell carcinoma of the lip, and a cytoplasmic and nuclear expression, slight and directly proportional to the epithelial disorganization in layers basal and suprabasal of actinic cheilitis and squamous cell carcinoma of the lip. It was also noted an increase in expression of cyclin D1 and Ki-67 in the basal layer as increased epithelial disorganization. There was a statistically significant association of cyclin expression D1 and Ki-67 in the suprabasal layer of the control group (p=0.030) and actinic cheilitis (p=0.001) and also in the inner region of squamous cell carcinoma of the lip (p=0.000). There was no significant correlation between the nuclear expression of ß-catenin and cyclin D1. Our results emphasize that ß-catenin, cyclin D1 and Ki-67 can be used as predictive biomarkers for lip cancer. Moreover, they suggest that ß-catenin and cyclin D1 acts on the lip carcinogenesis, in independent events signaling pathway/Wnt.(AU)

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores / Expression of RAGE in Helicobacter pylori infested gastric biopsies

Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

Análise imuno-histoquímica da Bcl-2, Bcl-6, c-Myc e ciclina D1 em linfomas de células B da região oral / Immunohistochemical analysis of Bcl-2, Bcl-6, c-Myc and Cyclin D in B cell lymphomas of the oral region

Neste trabalho foram analisados 30 casos de linfomas de células B da região oral, fixados em solução de formaldeído e incluídos em parafina, através da técnica de imuno-histoquímica para as proteínas c-Myc, Bcl-2, Bcl-6 e ciclina D1. Dos casos analisados 40% foram positivos para a marcação para c-Myc, 33,3% para a marcação para ciclina D1, 83,3% para a marcação para Bcl-2 e 53,3% para a marcação para Bcl-6. Todos os casos foram diagnosticados como linfomas difusos de grandes células B, o subtipo de linfoma com a maior casuística. A análise destas proteínas é de fundamental importância para o diagnóstico e direcionamento do tratamento de doenças hematopoiéticas, pois estão envolvidas em vários processos de controle da transcrição gênica, do ciclo celular e dos processos apoptóticos e o aumento do conhecimento sobre sua ação em diferentes subtipos de linfomas pode corroborar outros estudos

In this study, 30 cases of formalin-fixed and paraffin-embedded B-cell lymphomas of the oral region were submitted to immunohistochemistry for the detection of proteins c-Myc, Bcl-2, Bcl-6 and cyclin D1. Fourty percent (40%) of the studied cases were positive for c-Myc, 10% for cyclin D1, 83.3% for Bcl-2 and 53.3% for Bcl-6. The analysis of these proteins has fundamental importance for the diagnosis and treatment course of hematopoietic diseases, because they are involved in various processes controlling gene transcription and cell cycle. All cases were diffuse large B-cell lymphomas, the subtype with the highest incidence. The analysis of these proteins is very important for the diagnosis and treatment course of hematopoietic diseases, because they are involved in various processes controlling gene transcription, cell cycle and apoptotic processes and an increase in the knowledge of their action in different subtypes of lymphomas can corroborate to other studies

Correlation of cyclin D1 expression with aggressive DNA pattern in patients with tobacco-related intraoral squamous cell carcinoma.

Background & objectives: Cyclin D1 has been strongly implicated in cell proliferation particularly in the G1/S checkpoint of the cell cycle, and prognoses in human malignancies. We investigated the correlation between cyclin D1 overexpression and clinicopathological features as well as cell cycle parameters to understand its clinical significance in patients with tobacco-related oral squamous cell carcinoma (OSCC). Methods: Immunohistochemistry for cyclin D1 and DNA flowcytometry for cell cycle parameters was done on paraffin embedded tumour samples from 45 patients with OSCC Results: Higher expression of cyclin D1 was observed only in 30 (66.6%) of 45 cases that correlated with advanced age (P <0.02), higher tumour stage ((P<0.01), histological differentiation and lymph node metastasis (P <0.01). Analysis of nuclear DNA pattern revealed cyclin D1 immunoreactivity in tumours with aggressive DNA pattern such as aneuploidy ((P<0.05) and higher S phase fraction ((P<0.04). Interpretation & conclusions: Higher expression of cyclin D1 in oral cancer appears to be closely linked to cell proliferation, differentiation and lymph node invasion. Pre-operative evaluation of cyclin D1 in biopsy specimen may be useful in planning the most appropriate treatment strategies in patients with tobacco-related OSCC.

Adenocarcinoma of the esophagogastric junction: relationship between clinicopathological data and p53, cyclin D1 and Bcl-2 immunoexpressions / Adenocarcinoma da junção esôfago-gástrica: relação entre os dados cllnipatológicos e a imunoexpressão de p53, ciclina D1 e Bcl-2

Context: Esophagogastric junction adenocarcinoma has an aggressive behavior, and TNM (UICC) staging is not always accurate enough to categorize patient's outcome. Objectives: To evaluated p53, cyclin D1 and Bcl-2 immunoexpressions in esophagogastric junction adenocarcinoma patients, without Barrett's esophagus, and to compared to clinicopathological characteristics and survival rate. Methods: Tissue sections from 75 esophagogastric junction adenocarcinomas resected from 1991 to 2003 were analyzed by immunohistochemistry for p53, cyclin D1 and Bcl-2 using streptavidin-biotin-peroxidase method. The mean follow-up time was 60 months SD = 61.5 (varying from 4 to 273 months). Results: Fifty (66.7 percent) of the tumors were intestinal type and 25 (33.3 percent) were diffuse. Vascular, lymph node and perineural infiltration were verified in 16 percent, 80 percent and 68 percent of the patients, respectively. The patients were distributed according to the TNM staging in IA in 4 (5.3 percent), IB in 10 (13.3 percent), II in 15 (20 percent), IIA in 15 (20 percent), IIIB in 15 (20 percent) and IV in 16 (21.3 percent). Immunohistochemical analysis was positive for p53, cyclin D1 and bcl-2 in 68 percent, 18.7 percent and 100 percent, respectively. There was no association between immunoexpression and vascular and/or perineural invasions, clinicopathological characteristics and patients' survival rate. Conclusion: In this selected population, there was no association between the immunomarkers, p53, cyclin D1 and bcl-2 and clinicopathological data and/or overall survival.

Contexto: O adenocarcinoma da junção esôfago-gástrica tem um comportamento agressivo e o estádio TNM não é sempre suficiente para categorizar o paciente de acordo com a evolução do mesmo. Objetivo: Avaliar a imunoexpressão do p53, ciclina D1 e Bcl-2 em pacientes com adenocarcinoma da junção esôfago-gástrica sem esôfago de Barrett e comparar com as características clínicas e sobrevida. Métodos: Cortes histológicos de 75 adenocarcinomas da esôfago-gástrica ressecados de 1991 a 2003 foram analisados por imunoistoquímica para o p53, ciclina D1 e Bcl-2, usando-se o método da estreptavidina-biotina-peroxidase. O tempo médio de seguimento foi de 60 meses, DP=61,5 (variando de 4 a 273 meses). Resultados: Cinquenta (66,7 por cento) dos tumores eram do tipo intestinal e 25 (33,3 por cento) eram difusos. Verificou-se infiltração vascular, linfonodal e perineural em 16 por cento, 80 por cento e 68 por cento dos pacientes, respectivamente. O estádio TNM foi IA em 4 (5,3 por cento), II em 15 (20 por cento), IIIA em 15 (20 por cento), IIIB em 15 (20 por cento) e IV em 16 (21,3 por cento). A análise imunoistoquímica foi positiva para p53, ciclina D1 e Bcl-2 em 68 por cento, 18,7 por cento e 100, respectivamente. Não houve associação entre a imunoexpressão e invasão vascular ou perineural, características clinicopatológicas e sobrevida geral. Conclusão: Nesta população selecionada, não houve associação entre os imunomarcadores, p53, ciclina D1 e Bcl-2 e os dados clinicopatológicos e a sobrevida geral dos pacientes.

Signaling pathways in early onset sporadic breast cancer of patients in Indonesia.

AIM: to determine signaling pathways in breast cancers from patients aged 35 years old or younger and patients aged more than 35 years old. METHODS: this was a cross-sectional, comparative study of female breast cancer patients who were recruited and divided into two age groups, i.e. 35 years or younger and more than 35 years old. Specimens were obtained by biopsy or surgical removal of the tumors and were confirmed by histopathological examination. The expression of ER, IGF-1R, Her-2, MAPK, and cyclin D1 were measured using immunohistochemistry. RESULTS: ninety-three patients were recruited from September 2004 to December 2005. Forty-three patients were 35 years or younger. More than 90% of the patients within the two groups showed invasive ductal carcinomas and more than half of these tumors were grade 2. Immunohistochemical staining was successfully done in 90 patients. ER-alpha expression was negative in 33 breast cancers (78.6%) from patients less than 35 years old and 32 cancers (66.7%) of older patients. The expressions of IGF-1R, Her-2, MAPK, and cyclin D1 were positive, respectively in 17 (40.5%), 11 (26.2%), 28 (66.7%), and 7 (16.7%) cancers within the group of patients 35 years old or younger, and, respectively in 18 (37.5%), 11 (22.9%), 37 (77.1%), and 9 (18.8%) of cancers from patients more than 35 years old. CONCLUSION: there were no statistically significant differences in the expression of any of the biomarkers between the two groups. In all patients, ER was negative in 72.2% cases and MAPK was positive in 76.7% cases. Patients aged 35 years or younger showed similar ER, IGF-1R, Her-2, MAPK, and cyclin D1 expressions compared to cancers from patients more than 35 years old. These were predominantly ER-negative, suggesting that estrogen does not play a dominant role in their growth. The frequent expression of MAPK in these cancers raises the possibility that growth factors play a dominant role in their growth.

Comparison of Her-2, EGFR and Cyclin D1 in Primary Breast Cancer and Paired Metastatic Lymph Nodes: An Immunohistochemical and Chromogenic In Situ Hybridization Study

The significant advance in the development of molecular-targeting drugs has made an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of primary tumors as well as their matching lymph node metastases using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73 breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance between the primary lesion and the metastatic regional lymph nodes in 82%, 90%, and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable agreement between primary tumors and metastatic regional lymph nodes. Although a statistically significant agreement was found in Her-2 expression, a relatively high discordance rate (18%) raises a little concern. Our findings suggest that the Her-2 status can be reliably assessed on primary tumor but a possible difference can be found in Her-2, EGFR, and cyclin D1 status between the primary and the metastatic sites and this possibility should be concerned in patients considering molecular targeted therapy or patients with progress of disease.

Expression of cyclin D1 in endometrial hyperplasia and endometrial carcinoma.

This study investigates the role of cyclin D1 in 30 uterine surgical resection and endometrial biopsy specimens from 30 patients with simple hyperplasia (10 cases), complex hyperplasia (6 cases) and endometrial carcinoma (14 cases). Cyclin D1 immunohistochemistry was performed on 2-4 mm thick paraffin sections using labelled streptavidin biotin kit. Cyclin D1 expression was present in 2/6 (33%) cases of complex hyperplasia, 7/14 (50%) cases of endometrial carcinoma and none in simple hyperplasia. Difference in cyclin D1 immunopositivity in simple hyperplasia and endometrial carcinoma was statistically significant (p = 0.018) but the difference in cyclin D1 immunopositivity between complex hyperplasia and endometrial carcinoma was not statistically significant. Our study suggests that cyclin D1 over-expression may be an early event in endometrial carcinogensis. Since there was no difference in extent and intensity of cyclin D1 expression between complex hyperplasia and endometrial carcinoma, it appears that deregulation is maximal in complex hyperplasia.

Expressão de ciclina D1 e presença de metástase cervical de carcinoma epidermóide de boca / Cyclin D1 expression and cervical metastases in squamous cell carcinoma of the mouth

A metástase cervical é o fator de prognóstico mais relevante do carcinoma epidermóide de boca. Fatores clínicos e histológicos estão associados com o desenvolvimento da metástase cervical, porém a pesquisa de fatores moleculares está sendo amplamente realizada nos últimos anos. OBJETIVO: Observar a associação da expressão da ciclina D1 como fator de risco para a presença de metástase cervical. MATERIAL E MÉTODO: A expressão da ciclina D1 foi estudada e verificada sua associação com a metástase em 45 pacientes com câncer de boca. A leitura da expressão da ciclina D1 foi realizada pelo método estereológico. Características clínicas e histológicas foram pesquisadas e associadas com a presença de metástase. RESULTADOS: A expressão da ciclina D1 foi encontrada em 15 pacientes (33,4 por cento) e não esteve associada a fatores clínicos, histológicos e com a presença de metástase cervical, sendo sua expressão independente. O estadiamento clínico e as embolizações vasculares foram os fatores preditivos de maior relevância para o desenvolvimento de metástase. CONCLUSÕES: A expressão da ciclina D1, embora seja independente, não está associada com a presença de metástase cervical, enquanto que o estadiamento clínico e as embolizações vasculares estão.

Cervical metastasis represent the most relevant prognostic factor in carcinomas of the mouth. Clinical and histological factors are associated with the development of cervical metastasis; however, research on molecular factors has been broadly carried out in recent years. AIM: The aim of this study is to analyze the association of the Cyclin D1 as a risk factor for the presence of cervical metastasis. MATERIALS AND METHODS: Cyclin D1 expression was measured and the association between such substance and metastasis was found in 45 patients with mouth cancer treated by the author of this paper. Cyclin D1 presence was checked through the stereological method. Clinical and histological characteristics have been analyzed and associated with metastasis. RESULTS: Cyclin D1 expression was found in 15 patients but it was not associated with clinical and histological factors related to the presence of metastasis. Such conclusion indicates that Cyclin D1 is an independent protein. The most important predictive aspects related to metastasis development have been clinical staging and vascular embolization. CONCLUSIONS: Cyclin D1, although independent, is not associated with cervical metastasis, while staging and vascular embolization are.

Diagnostic Value of Galectin-3, HBME-1, Cytokeratin 19, High Molecular Weight Cytokeratin, Cyclin D1 and p27(kip1) in the Differential Diagnosis of Thyroid Nodules

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.

Synchronous Adenocarcinoma and Mantle Cell Lymphoma of the Stomach

Synchronous occurrence of mantle cell lymphoma (MCL) and gastric cancer in the same patient has not yet been reported in the English literature. MCL comprises 2.5-7% of non-Hodgkin's lymphomas and is characterized by a poor prognosis with a median survival probability of 3-4 years in most series. A 62-year-old man was referred to our hospital for evaluation of an abnormal gastric lesion. The endoscopic finding was compatible with type IIc early gastric cancer (EGC) in the middle third of the stomach, and a biopsy of the lesion proved to be carcinoma. Radical total gastrectomy with splenectomy and Roux-en-Y esophagojejunostomy were performed. The resected specimen revealed two grossly separated lesions. Postoperative histological examination reported both adenocarcinoma and MCL. Immunohistochemical staining showed positivity for CD5, CD20, and cyclin D1 in the infiltrated lymphoid cells. MCL is an aggressive non-Hodgkin's lymphoma, and the current treatment approach is still unsatisfactory. Further advancements in the understanding of the synchronous occurrence of both diseases, and more efforts on investigations of treatment are needed.

Expression of cyclin-D1 and apoptosis regulating protein BCL-2 in infiltrating ductal breast carcinoma [NOS]

Breast carcinoma is the most frequently diagnosed carcinoma affecting females contributing for about 30% of all female cancers in Egypt Estrogen and progesterone receptors [ER and PR] have been used as tools to identify patients eligible for adjuvant treatments, yet they present some limits, as the existence of dysfunctional receptors made some ER positive tumours non-responsive to antiestrogen therapy. In breast cancer, Bcl-2 expression has been reported to be associated with better outcomes in patients treated with either hormone- or chemo-therapy. Also, the expression of the protein cyclin D1 is detected in up to 50% of primary breast cancers. Cyclin D1 over expression has been strongly associated with well-differentiated, estrogen receptor-positive ductal tumors The present work aimed at determining the expression of cyclin D1 and bcl-2 proteins in some cases of infiltrating breast ductal carcinoma not otherwise specified [NOS,] and to assess any possible relationship between each marker and estrogen receptor status of the tumour tissue. Thirty cases of infiltrating ductal carcinoma [IDC], not otherwise specified [NOS], 17 cases of which were associated with axillary lymph node metastases, in addition to 5 cases of florid epithelial hyperplasia were included in the study. For all studied cases routine histopathological examination and immunohistochemical staining by ER, bcl-2 and cyclin D1 antibodies were done. ER status showed positive ER immunoreactivity in 21 cases [70%] out of 30 [2 cases/2 were grade I, 14 cases /18 were grade II and 5 cases/10 were grade III]. Positive Bcl-2 immunoreactivity was observed in 23 cases of the 30 IDC cases [76.66%]: 2 cases/2 were of grade I, 16 cases/18 of grade II and 5 cases/10 were of grade III. o A statistically significant relation was found between bcl-2 immunoreactivity and ER expression in the malignant cases [p<0.0001]. Cyclin D1 expression was detected in 20 cases of IDC [66.66%], staining was nuclear and diffuse: 2 cases out of 2 of WD carcinoma and 4 cases of MD carcinoma out of 18 showed strong staining [score 1], 10 cases of MD carcinoma out of 18 showed moderate staining [score 2], and 4 cases out of 10 of PD carcinoma showed weak staining [score 3].All the cyclin D1 positive 20 cases were also ER positive [100%]. A statistically significant relation was found between cyclin D1 immunoreactivity and ER expression [p<0.0004]. Bcl-2 was strongly associated with ER positivity in the majority of breast carcinomas but over expression of cyclin D1 protein correlated with poor prognosis and it was demonstrated that its over expression distinguished malignant breast carcinomas from premalignant breast lesions as the less differentiated high grade tumors exhibited a more intense nuclear stain and the non-neoplastic epithelial components were not stained

Expression of the G1-S Modulators in Hepatitis B Virus-Related Hepatocellular Carcinoma and Dysplastic Nodule: Association of Cyclin D1 and p53 Proteins with the Progression of Hepatocellular Carcinoma

Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.

Cell cycle regulators during human atrial development

OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.