Analysis of KIR gene frequencies and HLA class I genotypes in breast cancer and control group.

Breast cancer is the main cause of cancer-related death among women, with a 0.5% increase in incidence per year. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA alleles in patients with breast cancer and healthy controls. Two hundred thirty patients with breast cancer and 272 healthy controls were typed for HLA class I and KIR genes by PCR-SSO. When both groups were compared, the presence of inhibitory KIR2DL2 receptors was significantly higher in breast cancer patients than in healthy controls. No significant differences were found for HLA-C2 and HLA-Bw4. However, a higher frequency of HLA-C1 in breast cancer patients was observed. These findings suggest a potential role for the KIR gene system in breast cancer. Further studies to confirm this observation are warranted.

Prevalence of 185delAG and 5382insC mutations in BRCA1, and 6174delT in BRCA2 in women of Ashkenazi Jewish origin in southern Brazil.

Certain mutations in BRCA1 and BRCA2 genes are frequent in the Ashkenazi Jewish population. Several factors contribute to this increased frequency, including consanguineous marriages and an event known as a "bottleneck", which occurred in the past and caused a drastic reduction in the genetic variability of this population. Several studies were performed over the years in an attempt to elucidate the role of BRCA1 and BRCA2 genes in susceptibility to breast cancer. The aim of this study was to estimate the carrier frequency of certain common mutations in the BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) genes in an Ashkenazi Jewish population from Porto Alegre, Brazil. Molecular analyses were done by PCR followed by RFLP (ACRS). The carrier frequencies for BRCA1 185delAG and 5382insC were 0.78 and 0 respectively, and 0.4 for the BRCA2 6174deT mutation. These findings are similar to those of some prior studies but differ from others, possibly due to excluding individuals with a personal or family history of cancer. Our sample was drawn from the community group and included individuals with or without a family or personal history of cancer. Furthermore, increased dispersion among Ashkenazi subpopulations may be the result of strong genetic drift and/or admixture. It is therefore necessary to consider the effects of local admixture on the mismatch distributions of various Jewish populations.

Injeção intraoperatória de dextran-500-99m_tecnécio para identificação do linfonodo sentinela em câncer de mama / Intraoperative injection of technetium-99m-dextran 500 for the identification of sentinel lymph node in breast cancer

OBJETIVO: avaliar a eficácia da injeção intraoperatória para identificação do LS em câncer de mama com o uso do Dextran 500-99m-tecnécio (Tc) e analisar o tempo para marcação do linfonodo sentinela (LS) axilar. MÉTODOS: estudo prospectivo realizado entre abril de 2008 e junho de 2009 que incluiu 74 biópsias de LS em pacientes com câncer de mama em estádios T1N0 e T2N0. Após a indução anestésica, injetou-se de 0,5 a 1,5 mCi (18 a 55 MBq) de Dextran 500-99m-Tc filtrado 0,22 µm num volume de 5 mL de acordo com a técnica de injeção subareolar para a biópsia do LS. Após a marcação com o radiofármaco injetou-se 2 mL de azul patente. O tempo entre a injeção e a marcação na região axilar, a contagem com o probe do LS in vivo, ex vivo, background e o número de LS identificados foram documentados. Os dados foram analisados por meio da estatística descritiva pelo programa SPSS, versão 18. RESULTADOS: identificamos o LS em 100 por cento dos casos. A taxa de identificação com o probe foi de 98 por cento (73/74 casos). Um caso (1,35 por cento) estava marcado apenas com o azul. A dose média do radiofármaco aplicada foi 0,97 mCi±0,22. O tempo para marcação na região axilar, após a injeção subareolar, foi de 10,7 minutos (±5,7 min. ). Foram identificados, em média, 1,66 linfonodos marcados com o radioisotopo. CONCLUSÃO: o procedimento para identificação do LS com injeção intraoperatória do radiofármaco é oncologicamente seguro, apresentando conforto ao paciente e agilidade à equipe cirúrgica.

PURPOSE: to determine the efficacy of intraoperative injection of Dextran-500-99m-technetium (Tc) for the identification of the sentinel lymph node (SLN) in breast cancer and analyze time to label the SLN in the axillary region. METHODS: a prospective study between April 2008 and June 2009, which included 74 sentinel lymph node biopsies (SLNB) in patients with breast cancer in stages T1N0 and T2N0. After induction of anesthesia, 0.5 to 1.5 mCi of Dextran-500-99m-Tc filtered 0.22 µm in a volume of 5 mL was injected intraoperative using the subareolar technique for SLNB. After labeling with the radioisotope, 2 mL of patent blue was injected. The time elapsed between injection and the axillary hot spot, the in vivo and ex vivo counts of the hottest nodes, the background count, and the number of SLN identified were documented. Data were analyzed using descriptive statistics with SPSS program, version 18. RESULTS: we identified the SLN in 100 percent of cases. The rate of SLN identification with the probe was 98 percent (73/74 cases). In one case (1.35 percent) the SLN was labeled only with the blue dye. The mean dose of radioisotope injected was 0.97±0.22 mCi. The average time to label the SLN was 10.7 minutes (±5.7 min). We identified on average of 1.66 SLN labeled with the radioisotope. CONCLUSION: the procedure for SLN identification with an intraoperative injection of the radioisotope is oncologically safe and comfortable for the patient, providing agility to the surgical team.

[Intraoperative injection of technetium-99m-dextran 500 for the identification of sentinel lymph node in breast cancer]. / Injeção intraoperatória de dextran-500-99m_tecnécio para identificação do linfonodo sentinela em câncer de mama.

PURPOSE: to determine the efficacy of intraoperative injection of Dextran-500-99m-technetium (Tc) for the identification of the sentinel lymph node (SLN) in breast cancer and analyze time to label the SLN in the axillary region. METHODS: a prospective study between April 2008 and June 2009, which included 74 sentinel lymph node biopsies (SLNB) in patients with breast cancer in stages T1N0 and T2N0. After induction of anesthesia, 0.5 to 1.5 mCi of Dextran-500-99m-Tc filtered 0.22 µm in a volume of 5 mL was injected intraoperative using the subareolar technique for SLNB. After labeling with the radioisotope, 2 mL of patent blue was injected. The time elapsed between injection and the axillary hot spot, the in vivo and ex vivo counts of the hottest nodes, the background count, and the number of SLN identified were documented. Data were analyzed using descriptive statistics with SPSS program, version 18. RESULTS: we identified the SLN in 100% of cases. The rate of SLN identification with the probe was 98% (73/74 cases). In one case (1.35%) the SLN was labeled only with the blue dye. The mean dose of radioisotope injected was 0.97 ± 0.22 mCi. The average time to label the SLN was 10.7 minutes (± 5.7 min). We identified on average of 1.66 SLN labeled with the radioisotope. CONCLUSION: the procedure for SLN identification with an intraoperative injection of the radioisotope is oncologically safe and comfortable for the patient, providing agility to the surgical team.

A normativa do Hospital de Clínicas de Porto Alegre para o armazenamento e utilização de materiais biológicos humanos e informações associadas em pesquisa: uma proposta interdisciplinar / The Hospital de Clínicas de Porto Alegre normative for the storage and use of human biological materials and their associated information in research: an interdisciplinary approach

Este artigo apresenta a justificativa e o processo de elaboração do marco normativo do Hospital de Clínicas de Porto Alegre (HCPA) para o armazenamento e utilização de materiais biológicos humanos e suas informações associadas em atividades de pesquisa. Um grupo de trabalho multiprofissional se reuniu e discutiu todos os aspectos referentes a esta questão que envolve as atividades de biobanco e de biorrepositórios. Como produto deste trabalho é apresentada a Normativa Institucional.

This article presents the rationale and framework for developing the Hospital de Clinicas de Porto Alegre (HCPA) normative for storage and use of human biological material and their associated information on research activities. A multidisciplinary task force was established and all issues related to biobanks and biorepositories activities in periodic meetings were discussed; the final result is presented as an Institutional Normative.

Depression and perceptions of quality of life of breast cancer survivors and their male partners.

PURPOSE/OBJECTIVES: To assess differences in ways women with breast cancer evaluate their own quality of life (QOL) compared to perceptions of their partners and to identify factors that influence dissimilarities in QOL perceptions. DESIGN: Cross-sectional study. SETTING: Breast unit in southern Brazil. SAMPLE: 73 women with stage I-III breast cancer and their partners. Most participants were middle-aged, with partners of long-term cohabitation. METHODS: QOL was evaluated with the World Health Organization Quality of Life-Brief Form (WHOQOL-BREF), Beck Depression Inventory, and WHOQOL-BREF adapted for a third person. MAIN RESEARCH VARIABLES: Demographic and clinical features, QOL, partners' perceptions, and depression. FINDINGS: No differences were found between the perceptions of QOL in different domains between the patients and their partners. Depression in women seemed to be the only variable that interfered in a consistent manner with the congruity of the QOL assessments made by patients and their partners. CONCLUSIONS: Partners of women with breast cancer may be viewed as reliable surrogates to assess patients' QOL. IMPLICATIONS FOR NURSING: Partners' judgments of patients' QOL may be important in some circumstances, particularly when patients are not able to answer questions about their own QOL because of cognitive or functional limitations. Nurses must be aware that partners are the most frequent informal caregivers and should be included in the entire treatment process.

Biobanco do Hospital de Clínicas de Porto Alegre: aspectos técnicos, éticos, jurídicos e sociais / Hospital de Clínicas de Porto Alegre biobank: technical, ethical, legal and social issues

As atividades de pesquisa em saúde cada vez mais necessitam do armazenamento de materiais biológicos em biorepositórios e em biobancos. O estabelecimento de políticas institucionais para lidar com aspectos técnicos, éticos, legais e sociais é imprescindível para garantir a sua adequação. O Hospital de Clínicas de Porto Alegre está com um projeto de desenvolvimento em execução para propiciar que estas atividades sejam harmônicas e integradas.

Health research increasingly requires the storage of biological samples in biorepositories and in biobanks. The establishment of institutional policies to deal with technical, ethical, legal and social issues is essential to ensure the adequacy of these activities. Hospital Clínicas de Porto Alegre has a development project to bring harmony and integration to these activities.

Analysis of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast carcinoma.

Breast cancer is the most common neoplasia as well as the main cause of cancer-related death among women, experiencing a 0.5% increase in incidence per year. The disease results from a series of mutations in the DNA development and repair genes. Approximately 50% of human carcinomas present mutations in the TP53 gene. Polymorphisms of TP53 include codon 72 containing either arginine (CGC) or proline (CCC). Such polymorphisms may be involved in the susceptibility and predisposition to cancer, presenting a widely variable ethnic and geographic distribution. The arginine homozygous genotype seems to be a significant risk factor for breast cancer. The purpose of this study was to determine the frequency of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast cancer from southern Brazil, where this type of cancer has a high incidence, as well as its association with breast carcinoma and clinicopathological characteristics. Seventy-six patients suffering from invasive ductal breast cancer and 80 controls were analyzed, and samples were evaluated by PCR followed by restriction enzyme digestion. No statistical differences in terms of the genotype frequency (P=0.707) or the arginine and proline allele frequencies (P=0.469) involving codon 72 were found in patients compared to controls. Thus, statistical analysis did not suggest any association between the R72P polymorphism of the TP53 gene and invasive ductal carcinoma in the population studied. Additionally, no significant association with the clinicopathological characteristics presented by the breast carcinoma patients was found.

Tumor size as a surrogate end point for the detection of early breast cancer: a 30-year (1972-2002), single-center experience in southern Brazil.

The 30-year experience in improving detection of breast cancer in the Breast Unit of the Hospital de Clínicas, Federal University of Rio Grande do Sul, Brazil (1972-2002) is reported. We retrospectively analyzed the behavior of surrogate parameters of early breast cancer detection, such as the mean tumor diameter at diagnosis, clinical staging, as well as the percentage of breast conservative surgery along this period of three decades. From 2,103 identified women, 1,607 women met our criteria for study entry and had follow-up information, constituting our study cohort. Statistical tests were two-sided and considered significant at p < 0.05. There was a decrease of about 0.8 cm in the median tumor diameter over this 30-year period. The incidence of early-stage tumors increased progressively over time, and the percentage of patients presenting with stage I breast cancer doubled in 30 years. The Halsted procedure that represented 11.5% of surgeries in the 1970s is a very rare procedure nowadays (<1% of cases). Modified radical mastectomy was the procedure applied in about 50% of women with invasive breast cancer during these 30 years of observation. Notably, breast conservative surgery increased from 17.3% in the 1970s to 43.2% in the 2000s, while the decrease in tumor size and clinical staging was accompanied by an increased number of breast conservative surgical procedures. In geographic areas where coordinated preventive efforts are not thoroughly available, analysis of subsets of the patient population using tumor size as a surrogate represents an indirect way to observe long-term effects of prevention. The present study shows that tumor size is a surrogate for populations from developing countries too and gives scientific support for the design of continuous comprehensive programs of breast cancer prevention in this setting.

Chromosome analysis in 31 cases of benign and malignant breast tumors: a study in Brazil.

Cultures of 31 breast tumors, being 20 carcinomas and 11 benign lesions, were cytogenetically analysed. Clonal chromosome aberrations were detected in 16 carcinomas and in 4 benign lesions. Nine carcinomas and 2 benign lesions had multiple cytogenetically unrelated and related clones, whereas a single abnormal clone was observed in 7 carcinomas and in 2 benign lesions. Polyploid clones were found in 7 carcinomas and in 2 benign lesions. The presence of clonal chromosome aberrations and polyploid cells was not associated with the clinicopathologic parameters tested. Carcinomas had more clonal changes than benign lesions (p = 0.031), showing that cytogenetic features are of diagnostic value and that different chromosome anomalies might have different pathogenetic and prognostic significance.

Aconselhamento genético no câncer de mama / Genetic counselling in breast cancer

A descoberta dos genes BRCA1 e BRCA2, em 1994, e o posterior desenvolvimento dos testes genéticos fizeram surgir uma nova área de interesse dentro da Mastologia:o aconselhamento genético (AG). Apresentamos a nossa experiência na organizaçäo, no funcionamento e nos resultados iniciais do primeiro ano do Ambulatório de AG do nosso Serviço. Demonstrou-se que o risco de desenvolver câncer de mama percebido pelas pacientes é muito maior que o risco esperado para a idade e os fatores de risco aos quais estäo expostas, revelando a importância do AG no rebaixamento do nível de ansiedade. Verificou-se, também, que uma vez esclarecidas a respeito das indicaçöes e limitaçöes dos testes genéticos para identificaçäo de mutaçöes associadas à gênese do câncer de mama, a maioria das pacientes perde o interesse por ele. Avaliado o risco, propomos a nossa rotina de conduta baseada em diferentes faixas de magnitude de risco relativo: leve, moderado e severo. Na presente amostra, a totalidade das pacientes optou pelo seguimento rigoroso, näo tendo ocorrido nenhum caso de escolha de quimioprevençäo ou mastectomia profilática

Indivíduos férteis e inférteis frente aos tratamentos para a fertilidade

As novas técnicas de reprodução assistida têm proporcionado a inúmeros casais a realização do sonho de se tornarem pais e mães. Estas inovações tecnológicas têm, por outro lado, desencadeado a formulação de questionamentos de caráter psicossocial importantes e, ainda não consensuais, no que se refere às suas limitações e aos seus potenciais benefícios. Assim, as pessoas têm tido acesso a constantes, e muitas vezes contraditórias informações, advindas de divulgações da comunidade científica e de publicações opiniáticas da comunidade leiga através dos meios de comunicação de massa. O objetivo deste trabalho foi identificar como são representados, por indivíduos férteis e inférteis, os tratamentos disponíveis para infertilidade. Através da análise de variância multivariada, pôde-se observar algumas diferenças estatisticamente significativas entre grupos (férteis e inférteis) e entre sexos. Estas diferenças, no entanto, não foram suficientes para modificar a representação geral sobre cada um dos tratamentos. Os resultados permitiram a elaboração de um modelo de construto cognitivo dicotomizado, tanto para indivíduos férteis como para inférteis, no qual observa-se em um extremo os tratamentos que envolvem a participação de um terceiro não-médico doação de sêmen e 'barriga de aluguel' (envolvendo, concomitantemente a doação temporária de útero e a doação de óvulos) e, no outro, os métodos que não envolvem estas doações (AU)