Multiple SNPs Downregulate Gene Expression of Matrix Metallopeptidase 2 in MCF7 Breast Cancer Cells

@#Introduction: On a global scale, breast cancer contributes the highest cancer-related deaths in women due to metastasis which renders the treatments ineffective and non-targeted. The members of Matrix Metallopeptidases, particularly Matrix Metallopeptidase 2 (MMP2), are among the key players in breast cancer metastasis. In most cases, MMP2 was markedly upregulated and linked to poor prognosis. In a previous study, in silico analyses revealed that several coding single nucleotide polymorphisms (SNPs) of MMP2 were shown to reduce gene expression and mRNA stability of MMP2 in Malaysian breast cancer patients. Therefore, to validate the in silico predictions, the objective of this study was to determine the effects of multiple coding SNPs of MMP2 on the gene expression and mRNA stability of MMP2 in breast cancer cells. Methods: In the current study, breast adenocarcinoma MCF7 cells were transfected with MMP2 wild type and variant containing the coding SNPs. After confirmation of transfection by DNA sequencing, the gene expression level of MMP2 was evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) whereas mRNA stability of MMP2 was determined following treatment with actinomycin D. Results: MMP2 wild type and variant were successfully transfected in MCF7 cells based on sequencing and PCR analysis. It was found that the presence of coding SNPs lowered the gene expression level of MMP2, but not the stability of MMP2 mRNA. Conclusion: This study supports the in silico effects of MMP2 coding SNPs on its gene expression in an in vitro model.

Tumor-associated macrophage is correlated with survival and SOCS protein expression in canine mammary carcinoma / Correlação do infiltrado macrofágico com a sobrevida e a expressão da proteína SOCS no carcinoma mamário canino

The inflammatory infiltrate in the tumor microenvironment, particularly in mammary tumors, has aroused great interest in oncology, to play different roles in the progression or tumor regression dependent on the types and cell subsets involved. The present study aimed to evaluate (1) the occurrence and intensity of macrophage infiltration in the mammary carcinoma microenvironment, (2) the expression of SOCS1 and SOCS3 proteins in tumor associated macrophages, (3) any association between these parameters and tumor development, as well as survival rates in female dogs. Twenty-two female dogs diagnosed as carcinoma arising in a mixed tumor (CMT) by histopathology were divided into two groups following mastectomy: dogs without metastasis (CMT(-)=11) and those with metastasis (CMT(+)=11). The following parameters were analyzed: tumor size, lymph node metastasis, clinical stage, histological grade, distribution and intensity of inflammatory infiltrate, tumor macrophage quantification by immunohistochemical analysis of SOCS1 and SOCS3 expression, and immunophenotyping of peripheral blood leukocytes by flow cytometry. Dogs with the higher proportions of macrophages in the inflammatory infiltrate (≥400/tumor) also had higher survival rates in comparison with dogs with less macrophages. Immunostaining revealed higher proportions of SOCS3-positive macrophages in dogs without lymph node metastasis, while SOCS1-positive macrophages were predominant in dogs with metastasis (p<0.05). Multivariate analysis found associations between survival rate and clinical staging (p=0.025), histological grade (p=0.007), and the expression of MHC-CI in circulating monocytes (p=0.018). Higher SOCS3 expression in activated macrophages within the inflammatory infiltrate were considered indicative of an antitumor immune response, improved clinicopathological parameters and longer survival, whereas SOCS1-related activation was associated with tumor progression, metastasis development and reduced survival in female dogs with mammary carcinomas.(AU)

O infiltrado inflamatório no microambiente tumoral, particularmente nos tumores mamários, tem despertado grande interesse na oncologia, por desempenhar diferentes funções na progressão ou regressão tumoral, dependendo dos tipos e subtipos celulares envolvidos. O presente estudo teve como objetivo avaliar: (1) a ocorrência e a intensidade do infiltrado macrofágico no microambiente do carcinoma mamário; (2) a expressão das proteínas SOCS1 e SOCS3 nos macrófagos associados ao tumor; (3) qualquer associação relacionada ao prognóstico entre estes parâmetros e o desenvolvimento tumoral, assim como a taxa de sobrevida. Vinte e duas cadelas diagnosticadas com carcinoma em tumor misto (CTM) por exame histopatológico foram divididas em dois grupos após a mastectomia: cadelas sem metástase (CTM(-)=11) e cadelas com metástase (CTM(+)=11). Foram analisados os seguintes parâmetros: tamanho do tumor, metástase para linfonodo, estadiamento clínico, grau histológico, distribuição e intensidade do infiltrado inflamatório, quantificação dos macrófagos tumorais por análise imuno-histoquímica da expressão de SOCS1 e SOCS3, e imunofenotipagem dos leucócitos (monócitos e linfócitos) do sangue periférico por citometria de fluxo. Cadelas que apresentavam maiores proporções de macrófagos no infiltrado inflamatório (≥400/tumor) também tiveram maior taxa de sobrevida em comparação àquelas com menos macrófagos. A imunomarcação revelou maiores proporções de macrófagos SOCS3-positivos em cães sem metástase para linfonodo, enquanto que macrófagos SOCS1-positivos foram predominantes naqueles com metástase (p<0,05). A análise multivariada identificou associações entre a taxa de sobrevida e o estadiamento clínico (p=0,025), grau histológico (p=0,007) e a expressão de MHC-CI em monócitos circulantes (p=0,018). A maior expressão de SOCS3 nos macrófagos ativados foi considerada indicativa de uma resposta imune antitumoral, melhores parâmetros clínicos e maior taxa de sobrevida, ao passo que a ativação relacionada com SOCS1 foi associada à progressão tumoral, desenvolvimento de metástase e redução na taxa de sobrevida em cadelas com carcinoma mamário.(AU)

Pathological features of 78 metastatic or multicentric neoplasms involving the central nervous system in dogs / Aspectos patológicos e distribuição de 78 neoplasias metastáticas ou multicêntricas envolvendo o sistema nervoso central de caninos

Secondary neoplasms affecting the central nervous system (CNS) may occur through blood flow or direct extension. This condition occurrence has increased both due to a longer life expectancy of dogs, as well as with the employment of chemotherapeutics, which may increase the survival period and, thus, the odds of the occurrence of metastasis. The aim of this study was to analyze the epidemiological features, such as the age, breed and sex of the animals affected, as well as the gross and microscopic findings of the metastasis from neoplasms involving the CNS of 78 dogs, and, based on the data, estimate the occurrence and frequency of the metastatic or multicentric neoplasms. Females (71.79%) were most affected than males, with an average age of 9.5-years-old and a median of 10-years-old. Most of the cases had a multifocal distribution (73.07%), and epithelial neoplasms (50%) were the most common. Telencephalon was the most affected neuroanatomical region (61.1%). Mammary neoplasms were the most frequent (47.44%), followed by hemangiosarcoma (19.23%), lymphoma (10.26%) and melanoma (6.41%). Less common neoplasms included osteosarcoma, histiocytic sarcoma and lung carcinoma (2.56%). Mammary neoplasms were mainly composed of anaplastic and micropapillary carcinomas, of which only multifocal microscopic lesions were observed.(AU)

Neoplasias secundárias envolvendo o sistema nervoso central (SNC) podem ocorrer por via hematógena ou por extensão direta. A ocorrência desta condição vem aumentando devido à expectativa de vida mais longa dos cães, bem como através do uso de quimioterápicos, os quais podem ampliar a sobrevida e, portanto, as chances para a ocorrência de metástases. O objetivo deste estudo foi analisar os aspectos epidemiológicos, como idade, raça e sexo dos animais afetados, bem como caracterizar os achados macroscópicos e microscópicos de neoplasmas com metástases envolvendo o SNC de 78 caninos e, baseado nestes dados, estimar a ocorrência e a frequência de neoplasias metastáticas ou multicêntricas. Fêmeas (71,79%) foram mais afetadas do que machos, com uma idade média de 9,5 anos e mediana de 10 anos. A maior parte dos casos apresentava distribuição multifocal (73,07%), e neoplasias de origem epitelial (50%) foram as mais frequentes. A localização neuroanatômica mais afetada foi o telencéfalo (61,1%). As neoplasias mamárias foram as mais frequentes (47,44%), seguidas por hemangiossarcoma (19,23%), linfoma (10,26%) e melanoma (6,41%). Osteossarcoma, sarcoma histiocítico e carcinoma pulmonar (2,56%) foram neoplasias menos frequentes. Os tipos de neoplasmas mamários mais observados foram o carcinoma anaplásico e o carcinoma micropapilar, nesses dois tipos as lesões eram multifocais e observadas somente na microscopia.(AU)

Evaluation of serum concentrations of cortisol and thyroxine in bitches with early-stage mammary carcinoma / Concentrações séricas de cortisol e tiroxina em cadelas com carcinoma mamário em estádio inicial

In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.(AU)

Em vista do fato de neoplasias serem consideradas doenças crônicas que por meio de citocinas podem interferir na homeostase hormonal, hipotetizou-se que o carcinoma mamário, mesmo nos seus estádios iniciais, fosse capaz de alterar o equilíbrio dos eixos hipotalâmico-hipofisário-tireóideo e hipotalâmico-hipofisário-adrenal. Para tal, foram avaliadas as concentrações séricas de cortisol basal, tiroxina (T4), tiroxina livre (fT4) e tireotrofina (TSH) de 20 fêmeas caninas, inteiras, com diagnóstico histopatológico de carcinoma mamário grau 1 e estadiamento clínico I segundo a classificação da Organização Mundial da Saúde - OMS (T1N0M0). Os animais controle constituíram-se por 10 fêmeas caninas inteiras, em perfeitas condições de higidez, as quais foram pareadas, por idade, com aquelas portadoras de carcinoma mamário. Não foram encontradas diferenças significativas nas concentrações de cortisol basal, TSH, T4 e fT4 das cadelas portadoras de carcinoma mamário em estádio inicial quando comparadas às controles sugerindo que, mesmo considerados malignos, ainda não apresentam a capacidade de alterar as concentrações dos hormônios produzidos pelos eixos hipotalâmico-hipofisário-adrenal e tireóideo.(AU)

MicroRNA and cancer: a focus on mammary tumors in female dogs / MicroRNA e o câncer: um enfoque em tumores mamários de cadelas

ABSTRACT: Mammary tumors are the most frequent tumors reported in female dogs and have great relevance in veterinary oncology; however, little is known about the molecular mechanisms involved in the development of metastasis. An increasing number of human studies have suggested that epigenetic alterations, such as DNA methylation, miRNA, and histone modifications, are the predominant events leading to the metastatic phenotype in tumor cells and participate in regulating oncogenic signals associated with tumor spread. Among these epigenetic alterations, miRNAs have stood out in recent years, presenting a fundamental role in tumorigenesis. There are still few studies evaluating the role of miRNAs in canine mammary tissues. Thus, this paper aims to review the role of miRNAs in cancer with a special focus on canine mammary tumors.

RESUMO: Os tumores mamários caninos são considerados os mais frequentes em cadelas, além de apresentarem grande relevância na oncologia veterinária, porém a doença metastática ainda é um desafio que compreende mecanismos moleculares não totalmente esclarecidos. Um número crescente de estudos na medicina humana tem sugerido que alterações epigenéticas, tais como metilação do DNA e modificação das histonas são eventos predominantes na célula tumoral para aquisição do fenótipo metastático, participando da regulação de sinais oncogênicos associados com a disseminação do tumor. Dentre as alterações epigenéticas, os miRNAs se destacaram nos últimos anos apresentando um papel fundamental na tumorigênese. Ainda existem poucos estudos avaliando o papel dos miRNAs em tecidos mamários caninos. Assim, com este trabalho objetiva-se revisar o papel dos miRNAs no câncer com foco especial nos tumores de mama de cadelas.

A simultaneous occurrence of feline mammary carcinoma and uterine cystic endometrial hyperplasia in a cat

At the time of visiting, the cat was 6-year-old female Siamese cat. The mammary mass was solid and firm and measured 2 × 5 cm2 in greatest diameter. The uterus revealed thick uterine horn and cross sectioned wall. Histopathologically, the mammary mass revealed feline mammary carcinoma. In the uterus, cystic endometrial hyperplasia was observed. Feline leukemia virus positive reaction was detected by polymerase chain reaction. As far as we know, this is the first report of the simultaneous feline mammary carcinoma and uterine endometrial cystic hyperplasia with Feline leukemia virus infection in a cat.

Carcinoma inflamatório de mama ­ Uma abordagem comparada / Inflammatory mammary carcinoma - A comparative approach / Carcinoma inflamatório de mama - Un enfoque comparativo

O Carcinoma Inflamatório de Mama (CIM) é um neoplasma maligno de rápida evolução que apresenta baixa ocorrência tanto em cadelas quanto em mulheres. É pouco relatado pelos médicos veterinários no Brasil, fato que pode ser relacionado à falta de conhecimento da doença associado à necessidade da relação dos achados clínicos com exame histopatológico para o diagnóstico definitivo. Esse neoplasma também acomete a glândula mamária de mulheres, nas quais demonstra características clássicas de inflamação como dor, turgor de pele e aumento de temperatura local. Para diagnóstico definitivo é considerado a presença de êmbolos de células tumorais em canais linfáticos da derme associados aos sinais clínicos de inflamação. Devido ao grau de infiltração local, os sinais de inflamação e a presença de êmbolos em linfáticos, o paciente humano e veterinário apresentam prognóstico desfavorável. O CIM é pouco responsivo à quimioterapia e devido às características de inflamação, não apresenta indicação cirúrgica na maioria dos casos. Devido à agressividade do CIM em mulheres e nas cadelas, do prognóstico desfavorável e das restritas opções terapêuticas essa revisão objetiva descrever os avanços das opções terapêuticas além do tratamento paliativo na literatura atual além de apresentar uma abordagem comparada, considerando a cadela um modelo de estudo para a doença na mulher.

The Inflammatory Mammary Carcinoma (IMC) is a low-occurrence malignant neoplasm with rapid evolution that affects dogs and women. There are few reports of this disease in the Brazilian veterinary literature, which may be related to the lack of knowledge of the disease associated with the need of relating clinical findings to histopathology exams for definitive diagnosis. This neoplasm also affects the mammary glands in women, which demonstrates classical signs of inflammation such as pain, skin turgor and increased local temperature. The diagnosis considers the presence of tumor cell emboli in the lymph vessels in the dermis associated with clinical signs of inflammation. Due to the degree of local infiltration, signs of inflammation and the presence of lymph emboli, both human and veterinary patients have unfavorable prognosis. The IMC is poorly responsive to chemotherapy and due to its inflammation characteristics, in most cases, surgical removal is not recommended. Due to the aggressiveness of the IMC on women and bitches, poor prognosis and limited therapeutic options, this paper aims to describe the advances of therapeutic options beyond palliative care in current literature, as well as presenting a comparative approach considering the bitch as a study model for treating the disease in women.

El carcinoma inflamatorio de mama (CIM) es una neoplasia maligna de evolución rápida que tiene una baja incidencia tanto en perras como en mujeres. Es poco relatado por médicos veterinarios en Brasil, hecho que puede estar relacionado a la falta de conocimiento de la enfermedad, asociada a la necesidad de la relación de los hallazgos clínicos con examen histopatológico para el diagnóstico definitivo. Esta neoplasia también afecta a las glándulas mamarias de mujeres, lo que demuestra características clásicas de inflamación, como dolor, la turgencia de la piel y el aumento de la temperatura local. Para el diagnóstico definitivo se considera la presencia de émbolos de células tumorales en los canales dermis ganglios, asociados con los signos clínicos de inflamación. Debido al grado de infiltración local, los signos de inflamación y la presencia de embolias en el linfático, el paciente humano y veterinario presentan pronóstico desfavorable. El CIM es poco sensible a la quimioterapia y debido a las características de inflamación no presenta indicación quirúrgica en la mayoría de los casos. Debido a la agresividad del CIM en mujeres y perras, del pronóstico desfavorable y de las restrictas opciones terapéuticas, esa investigación tuvo como objetivo revisar el progreso de las opciones terapéuticas además del tratamiento paliativo en la literatura actual, allende presentar un enfoque comparativo, teniendo en cuenta que la perra es un modelo de estudios para la enfermedad en mujeres.

Phytochemical analysis and anticancer capacity of Shemamruthaa, a herbal formulation against DMBA- induced mammary carcinoma in rats

OBJECTIVE@#To investigate the bioactive constituents of Shemamruthaa (SM), a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation (LPO), antioxidant status, citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene (DMBA) induced mammary carcinoma in rat model.@*METHODS@#Adult female Sprague-Dawley rats were used for the study and were divided into four groups. Group I served as control and Group II rats were induced mammary carcinoma by administration of DMBA (25 mg/kg b.w.) orally. The normal and cancer-induced rats (Group III) were treated with SM (400 mg/kg b.w./day) orally by gastric incubation for 14 days. Group IV rats served as SM-treated control animals.@*RESULTS@#Cancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants, citric acid cycle enzymes, electron transport chain enzymes and cytochrome contents in the mammary tissue. Treatment with SM brought back the aforementioned biochemical parameters to near normal.@*CONCLUSIONS@#From the results, it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO, prevention of membrane damage and restoring membrane integrity.

Modulation of lipid peroxidation and antioxidant status upon administration of 'Shemamruthaa' in 7,12-dimethylbenz[a]anthracene induced mammary carcinoma bearing rats

Objective: To investigate the therapeutic efficacy of a Shemamruthaa (SM), (combination of Hibiscus rosasinensis (H. rosasinensis) flowers, fruits of Phyllanthus emblica (P. emblica) and pure honey in definite ratio), against lipid peroxidation (LPO) and antioxidant status in experimentally induced mammary carcinoma rats. Methods: Adult female Sprague-Dawley rats were used for the study and were divided into four groups. Group I control animals received standard pellet diet and water ad libitum. Group II rats were induced with 7,12-dimethyl benz[a]anthracene (DMBA) (25 mg in 1 mL olive oil) by gastric intubation, whereas another set of DMBA-induced rats were treated with SM (400 mg/kg body weight/d) in olive oil orally by gastric intubation for 14 d after 3 months of induction period (group III). Group IV rats served as SM-treated control animals. At the end of the experimental period, the rats were anaesthetised and sacrificed and used for biochemical measures and histology studies. Results: The LPO was increased and antioxidant levels were decreased in the serum, liver and mammary tissues of cancer-induced rats. The administration of SM drug significantly (P<0.05) decreased LPO and reversed the status of antioxidants to near normal level in cancer-bearing animals. Conclusions: The results obtained indicate the additive and synergistic action of constituents’ plants in the SM drug against oxidative damage and its protective role in DMBA induced mammary cancer.

Extracts of red yolk from duck eggs inhibit metastasis of human mammary carcinoma (4T1) cells in mice

The aim of the present study was to investigate the in vivo anti-metastatic activity of the red pigments of red yolk eggs laid by the ducks dieting on Potamogeton cripus L on the mammary carcinoma (4T1). The pigments were extracted with petroleum ether and acetone (2:1, v/v). BALB/c mice were divided into three groups (n=6), fed with the extracts at 150 mg/kg body weight (BW)/day (DEYE-H) or at 50 mg/kg BW/day (DEYE-L) and identical buffer without the extract (control group). The extracts were administered for 34 days. The treatment significantly inhibited the growth of orthotopical 4T1 tumour (DEYE-H vs control, 1:2; DEYE-L vs control, 2:3) and reduced the metastasis of tumour in the lungs (DEYE-H vs control, 4:7; DEYE-L vs control, 5:7), without statistical difference of body weight among the three groups.

Correlação da mamografia com o exame clínico e incidência do câncer de mama na população de Xangri-Lá / Correlation of breast clinical exam with mammography and incidence of breast cancer in the population of Xangri-Lá/RS

Foram publicados na Revista Brasileira de Mastologia dados importantes sobre a população feminina de Xangri-Lá/RS, demonstrando alta incidência de câncer de mama. Objetivos: avaliar as mulheres de Xangri-Lá através do exame clínico das mamas (ECM) e da mamografia (MMX). Estimar a incidência e a prevalência do câncer de mama no período de 2008 e 2009. Métodos: estudo transversal de base populacional, 811 mulheres do município de Xangri-Lá/RS foram incluídas. Categorizamos o ECM e a MMX em alterado e normal. Além disso, a amostra foi dividida em faixas etárias para o cálculo de sensibilidade (S), especificidade (E), prevalência (P) e valores preditivos (VP) do ECM em relação à MMX. Foram calculadas incidência e prevalência do câncer de mama. Resultados: a taxa bruta de incidência de câncer de mama para o ano é de 79,1/100.000 mulheres, e a taxa de prevalência é de 8/1000 mulheres. O ECM e a MMX parecem ser mais acurados no grupo de mulheres com mais de 50 anos. Confirmaram-se 5 casos de câncer de mama, um caso de linfoma e um caso de hiperplasia atípica focal. Discussão: os nossos dados mostraram uma maior S e VP do ECM comparado com a MMX nas mulheres com faixa etária superior a 50 anos. Trata-se de uma população com alta incidência e prevalência de câncer de mama. Conclusões: a incidência bruta anual do câncer de mama mostrou-se alta, porém é o esperado para o Estado. Além disso, trata-se de uma população com alta frequência de fatores de risco

Important data was published in Revista Brasileira de Mastologia demonstrating high incidence of breast cancer in the female population of Xangri-Lá, state of Rio Grande do Sul, Brazil. Aim: to evaluate women from Xangri-Lá by clinical breast examination (CBE) and mammography (MMX), as well as to estimate the incidence and prevalence of breast cancer between 2008 and 2009. Methods: cross-sectional population-based study including 811 women of Xangri-Lá. CBE and MMX were categorized as normal or abnormal and the sample was divided into age groups to evaluate the sensitivity (Se), specificity (Sp), prevalence (P) and predictive values (PV) of CBE in relation to MMX in both groups. Furthermore, breast cancer incidence and prevalence were calculated for the period. Results: breast cancer incidence was 79.1/100,000 and breast cancer prevalence was 8/1000 for this sample. MMX and ECM seem to be more accurate in the group of women over 50 years, probably by modifications in breast anatomy. This study confirmed five cases of breast cancer, a lymphoma case and a case of atypical focal hyperplasia. Discussion: our data showed a higher Se and PV of CBE as compared with MMX in women aged less than 50 years, which is a population with high breast cancer incidence and prevalence. Conclusions: breast cancer annual incidence was high, but this finding is expected for the study area. Moreover, the population under analysis has a high frequency of risk factors

Caracterização anatomopatológica e imunofenótipica de carcinomas de mama em mulheres jovens / Pathological and molecular characterization of breast carcinomas of young women

Objetivos: Analisar características anatomopatológicas e perfil imuno-histoquímico dos carcinomas de mama em mulheres até os 35 anos. Método: Estudo retrospectivo com análise de casos recebidos no período de 1997 a 2007. Foram identificados 909 (6,6%) casos de jovens, dos quais 314 possuíam blocos de parafina disponíveis. Foi selecionado um grupo controle de 81 pacientes acima de 60 anos. Todos os casos foram revisados quanto a características anatomopatológicas. A pesquisa imuno-histoquímica de RE, RP e HER2 foi realizada em 291 casos de mulheres jovens e em 74 acima de 60 anos. Os tumores foram categorizados como luminal (RE e/ou RP positivo), HER2 (RE e RP negativos e HER2 positivo) e triplo-negativo (RE, RP e HER2 negativos). Resultados: O tipo histológico ductal invasivo foi o mais frequente nos dois grupos (95,2% em jovens e 83,90% acima de 60 anos). A frequência do tipo lobular foi menor no grupo jovem (2,5% x 12,3%), embora o subtipo pleomórfico tenha sido mais frequente. Pacientes jovens apresentaram mais frequentemente tumores de alto grau (41,7% x 28,4%) e tendência a tumores circunscritos (8,2% x 7,4%) e com necrose (23,2% x 16,0%). O perfil luminal foi mais frequente nos dois grupos, embora com proporção menor nas jovens (64,9% x 81,1%). Estas apresentaram maior frequência do perfil triplo-negativo (27,1% x 17,6%), mais superexpressão de HER2 (16,5% x 5,4%), e maior frequência do perfil HER2 puro (7,9% x 1,3%). Conclusões: Os resultados apontam para diferenças intrínsecas nos carcinomas em jovens, caracterizadas por perfis morfológico e imuno-histoquímico mais agressivos.

Aims: To analyse pathological features and immunohistochemical profile of breast carcinomas in women 35 years or less. Methods: Retrospective study with analysis of the cases received from 1997 to 2007. We identified 909 (6.6%) cases of breast cancer in young women, 314 of them with available paraffin blocks. A control group of 81 patients above age of 60 was selected. AlI the cases were revised regarding histological features. The immunohistochemical detection of ER, PR and HER2 was carried on 291 cases of young women and 74 in olders. The tumors were categorized as luminal (positive ER and/or PR), HER2 (negative ER and RP, and positive HER2), and triple-negative (negative ER, PR and HER2). Results: The ductal histological type was the most frequent one in the two groups (95.2% in young and 83.9% above 60 years). Infiltrative lobular carcinoma was less frequent in the young group (2.5% x12.3%), although the pleomorphic subtype was more frequent. Young women more often presented with high grade tumors (41.7% x 28.4%) and showed a trend to more circumscribed tumors (8.2% x 7.4%) and necrosis (23.2% x 16.0%). The luminal profile was more frequent in the two groups, although with lower frequency among younger (64.9% x 81.1%). These presented more triple-negative profile (27.1% x 17.6%), more overexpression 01 HER2 (16.5% x 5.4%), as well as the molecular profile HER2 (7.9% x 1.3%). Conclusions: The results point to intrinsic differences in the tumors arising in young women characterized by more aggressive morphological and immunohistochemical profiles.

D2-40, a novel lymphatic endothelial marker: identification of lymphovascular invasion and relationship with axillary metastases in breast cancer

BACKGROUND: Studies of lymphatic vessels were limited by the lack of specific markers. Recently, they have become possible due to the release of new D2-40 antibody, a selective marker for lymphatic endothelium. The aim of our study was to compare neoplastic invasion in lymphatic and blood vessels detected in hematoxylin and eosin (H&E) and immunohistochemistry-stained sections. METHODOLOGY: A total of 123 cases of invasive mammary carcinomas were studied and sorted out into three subgroups according to axillary staging (macrometastasis, micrometastasis and lymph node negative). Lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were initially evaluated in histological H&E and immunohistochemistry-stained sequential sections. Lymphatic and blood vessel invasions were assessed by immunohistochemistry, employing D2-40 and CD31 antibodies, respectively. LVI and BVI were related to size, type, histologic grade of primary tumors, and the presence of metastasis. RESULTS: LVI was detected through H&E staining procedure in 17/123 cases (13.8 percent), and through immunohistochemistry procedure in 35/123 cases (28.5 percent) (kappa = 0.433). BVI was detected through H&E in 5/123 cases (4.1 percent), and through immunohistochemistry in 19/123 cases (15.4 percent) (kappa = 0.198). LVI and BVI were positively related to higher histologic grade of primary tumors (p < 0.05). LVI was also positively related to the presence of macrometastasis. CONCLUSION: The detection of lymphatic and blood vessel invasions through immunohistochemistry employing D2-40 and CD31 was higher than the detection through H&E, and it was related to higher tumor grade and metastasis in axillary lymph nodes.

INTRODUÇÃO: Estudos de vasos linfáticos eram limitados pela ausência de marcadores endoteliais linfáticos específicos. Recentemente, eles se tornaram possíveis após liberação comercial do novo anticorpo D2-40, marcador seletivo para endotélio linfático. O objetivo do nosso estudo foi comparar invasão neoplásica em vasos linfáticos e sanguíneos detectada em secções coradas pela hematoxilina e eosina (HE) e imuno-histoquímica (IIQ). MATERIAIS E MÉTODOS: Foram estudados 123 casos de carcinomas mamários invasores subdivididos em três subgrupos de acordo com o estadiamento axilar: macrometástases (Mac-Met), micrometástases (Mic-Met) e linfonodo negativo (LNN). Invasão de vasos linfáticos (IVL) e de vasos sangüíneos (IVS) foi inicialmente avaliada em secções histológicas coradas pela HE e através da IIQ realizada em cortes seqüenciais. A invasão de vasos linfáticos e sanguíneos foi avaliada pela imuno-histoquímica, empregando-se respectivamente os anticorpos D2-40, e CD31. IVL e IVS foram relacionadas com tamanho tumoral, tipo e grau histológico dos tumores primários e com a presença de metástases. RESULTADOS: IVL foi observada pela HE em 17/123 casos (13,8 por cento) e pela IIQ em 35/123 casos (28,5 por cento) (kappa = 0,433). IVS foi observada pela HE em 5/123 casos (4,1 por cento) e pela IIQ em 19/123 casos (15,4 por cento) (kappa = 0,198). IVL e IVS estavam positivamente relacionadas com maior grau histológico dos tumores primários (p < 0,05). IVL também estava positivamente relacionada com a presença de macrometástases. CONCLUSÃO: A detecção IIQ, respectivamente por D2-40 e CD31, de invasão de vasos linfáticos e sanguíneos foi maior que a detecção feita em cortes corados pela HE e relacionou-se com maior grau tumoral e metástases em linfonodos axilares.

Expression of Human Papillomavirus in Mammary Carcinoma and its Possible Mechanism in Carcinogenesis / 中国病毒学·英文版

To explore the role of Human papillomavirus (HPV) in mammary carcinogenesis, the expression of the HPV-16, iNOS, P53 and hTERT proteins in breast carcinomas and their relationships were investigated. 52 samples of breast cancer and 16 samples of benign breast tumors were assayed using the immunohistochemical SP method for detection of protein expression levels. The expression of HPV-16, iNOS, P53 and hTERT proteins in a mammary carcinoma was 44.2%, 57.7%, 63.5% and 59.6% respectively, which was significantly greater than the corresponding levels in the benign group. The expression of iNOS, P53 and hTERT was correlated with the presence of an HPV-16 infection in a mammary carcinoma (P<0.05). The connection between these events might also involve the iNOS, mutated type P53 and the hTERT protein.

Carcinoma em tecido mamário ectópica: aspectos de imagem (mamografia, ultra-sonografia e ressonância magnética) / Carcinoma in ectopic breast tissue: imaging aspects (mammography, ultrasonography and magnetic resonance imaging)

Nos últimos três anos foram realizadas 30.000 mamografias no Departamento de Diagnóstico por Imagem da Universidade Federal de São Paulo/Escola Paulista de Medicina, sendo que em 0,23% delas foi observado tecido mamário acessório. Relatamos um caso de paciente de 44 anos de idade, feminina, que apresentava nódulo endurecido, aderido ao subcutâneo, em topografia inframamária à direita. À ultra-sonografia observou-se imagem nodular sólida hipoecogênica, com contornos irregulares, medindo 1,4 cm. À ressonância magnética visualizou-se curva de realce tipo II (platô). Após biópsia, foi diagnosticado denocarcinoma mamário. O carcinoma nas mamas acessórias costuma apresentar aspecto histopatológico indiferenciado e disseminação mais precoce, determinando pior prognóstico. Por este motivo, é de fundamental importância sua detecção nos estágios iniciais, permitindo, dessa forma, a instituição precoce do tratamento e possibilitando maiores chances de cura.

Over the last three years 30,000 mammograms were performed in the Department of Diagnostic Imaging of Universidade Federal de São Paulo/Escola Paulista de Medicina. Accessory breast tissue was observed in 0.23% of the individuals. We report a case of a 44-year-old woman presenting a hard nodule adhered to the subcutaneous tissue in right inframammary topography. At ultrasonography, a hypoechogenic solid nodule with irregular contour measuring 1.4 cm was observed. Magnetic resonance imaging showed type II (plateau) dynamic curve. Breast adenocarcinoma was subsequently diagnosed by biopsy. Accessory breast carcinomas generally present with an ill-defined histopathological aspectand early dissemination. Early detection is essential to begin treatment in the initial stages, with better chances of cure.

Effect of Psychological Intervention on Patients with Mammary Carcinoma / 中国康复理论与实践

@#ObjectiveTo investigate the effect of psychological intervention on quality of life (QOL) of patients with mammary carcinoma.Methods64 patients with mammary carcinoma were divided into intervention group (n=36) and control group (n=28), and psychological status and QOL of patients of two groups were analyzed after treatment.ResultsThe psychological status and QOL of intervention group was better than that of control group (P<0.05～0.001).ConclusionThe psychological intervention in full stage being in hospital can improve QOL of patients with mammary carcinoma, and it is clinically significant to improve cure rate and survival rate of patients.

Reversal of Adriamycin Resistance in Human Mammary Cancer Cells by Small Interfering RNA of MDR1 and MDR3 Genes / 华中科技大学学报（医学）（英德文版）

The purpose of this paper is to investigate the reversal effect of small interfering RNA (siRNA) targeting MDR1 and MDR3 genes on the resistance of MCF-7/ADR cells to adriamycin.siRNA plasmid vector targeting MDR1 and MDR3 genes was transfected into MCF-7/ADR cells, and then was stained with Annexin-V FITC (fluorescein isothiocyanate conjugated) to detect the early stage cell apoptosis by flow cytometry (FCM). 50 ％ inhibition concentration (IC50) of adriamycin for MCF-7/ADR cells was determined by MTT method. MDR1 and MDR3 mRNA was assessed by RT-PCR. Treatment of MCF-7/ADR cells with the two kinds of siRNAs resulted in a reversal of adriamycin resistance of MDR to different extents. 1) The apoptosis efficiency of MDR1 and MDR3siRNA vector after transfection was (18.21±1.65) ％ and (9.07±2.16) ％ respectively (P＜0.05), and there was significant differences in the apoptosis efficiency between pSuppressor Neo vector and the MDR 1 siRNA or MDR3 siRNA vector (P＜0.01); 2 ) The reversal effect of MDR 1 siRNA is higher than that of MDR3 siRNA (P＜0.05); 3 ) The expression of MDR1 and MDR3 mRNA can be restrained by pSuppressor Neo MDR1 and MDR3 siRNA respectively, and the reduction in the mRNA level was in a time-dependent manner (P＜0.01). MDR1 and MDR3 gene silencing can enhance intracellular adriamycin accumulation in MCF-7/ADR cells, improve sensitivity of MCF-7/ADR cells to adriamycin, and induce cell apoptosis. The reversal effect of adriamycin resistance by siRNA of MDRlwas more effective than that of MDR3.

An experimental study on the effect of somatostatin in antagonizing the maladjustment of sexual hormones homeostasis induced by tamoxifen / 重庆医科大学学报

Objective:To investigate the effect of somatostatin (SST) analog octreotide (OCT) in antagonizing the maladjustment of sexual hormones homeostasis induced by tamoxifen(TAM) in rat.Methods:Eight weeks after DMBA(a single dose 100mg/kg body weight by subcutaneous injection) application,the female Wistar rats were randomized to control and treatment groups.Rats in treatment groups underwent TAM(1mg/kg 5 times weekly for 14 weeks by subcutaneous injection),OCT(0.1mg/kg bid for 14 weeks by subcutaneous injection),or the combination of both.The levels of sexual hormones (estradiol,progesterone,prolactin,follicle stimulating hormone,luteinizing hormone) were assessed by enzyme immunoassay(EIA).Results:The levels of estradiol and progesterone in serum were remarkably higher in TAM group(21.69pg/ml,6.14ng/ml) than in control group(16.92pg/ml,4.13ng/ml) respectively(P