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INTRODUCTION: Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. METHODS: Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. RESULTS: CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. CONCLUSIONS: PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
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Adenocarcinoma , Antígeno B7-H1 , Antígenos HLA-G , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Pessoa de Meia-Idade , Idoso , Microambiente Tumoral/imunologia , Antígeno B7-H1/metabolismo , Antígenos HLA-G/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Prognóstico , Linfócitos T CD8-Positivos/imunologia , Adulto , Linfócitos T Reguladores/imunologia , Idoso de 80 Anos ou mais , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologiaRESUMO
Programmed death ligand 1 (PD-L1) has been investigated in various types of cancer; however, the role of PD-L1 expression in breast cancer remains controversial. We performed a systematic review and meta-analysis to assess the association of PD-L1 expression with clinicopathological variables, overall survival (OS), and disease-free survival (DFS) in invasive breast cancer. A total of 965 articles were included from CINAHL, Embase, PubMed, and Scopus databases. Of these, 22 studies encompassing 6468 cases of invasive breast cancer were included in the systematic review, and 15 articles were included in the meta-analysis. PD-L1 expression was associated with age ≥ 50 years, lymph node status-negative, progesterone receptor-negative, Ki67 ≥ 20%, and human epidermal growth factor receptor 2 (HER2)-negative. PD-L1 positivity was associated with worse OS (hazard ratio, HR, 2.39; 95% confidence interval, CI, 1.26-3.52; p =< 0.000); however, there was no significant improvement in DFS (HR 0.17; 95% CI -0.12-0.46; p =< 0.252). PD-L1 positivity was significantly associated with the clinicopathological characteristics of favorable and unfavorable prognoses. However, the final clinical outcome was associated with lower OS and had no significant association with DFS.
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Objetivo: Determinar a prevalência de doença de Paget da mama (DPM) entre os casos de carcinomas ductais diagnosticados em um centro universitário, entre 2003 e 2007, descrever as características clínicas e analisar a sobrevida desses casos. Métodos: Estudo de coorte retrospectiva, por meio da revisão de prontuários médicos. Foi realizada análise de frequência para todas as variáveis e utilizada curva de Kaplan-Meier para a representação da sobrevida global. Resultados: De 278 casos de carcinomas ductais de mama, houve 14 casos de DPM, determinando prevalência de 5,0%. Um caso foi excluído da análise por apresentar dados incompletos. A média de idade ao diagnóstico foi de 57,1 (±11,2) anos. Dos casos analisados, 11 (84,6%) apresentavam tumor palpável, e 9 (69,3%), lesão do complexo aréolo-papilar (CAP). Apenas um caso não foi submetido à mastectomia, por óbito durante quimioterapia neoadjuvante. Radioterapia foi realizada em 6 casos (46,2%), quimioterapia, em 11 casos (84,6%), e endocrinoterapia, em 6 casos (46,2%). A imunoistoquímica identificou 5 casos (38,5%) com expressão de receptores hormonais e 12 casos (92,3%) com superexpressão de HER2. A sobrevida global das pacientes foi de 61,5 (±13,4) meses e não houve recidiva local após um tempo médio de seguimento de 75,8 meses. Conclusão: Observou-se prevalência de DPM associada a carcinomas invasores com estádio clínico avançado, o que possivelmente ocasionou sobrevida global inferior à observada em estudos prévios para a região.
Objective: To determine the prevalence of Paget's disease of the breast (PD) among cases of ductal carcinomas diagnosed in a university hospital between 2003 and 2007; describe clinical characteristics and analyze the survival of these cases. Methods: Retrospective cohort study, by reviewing medical records. Frequency analysis was performed for all variables and used Kaplan-Meier curve for the representation of overall survival. Results: In 278 cases of breast ductal carcinoma, 14 cases were PD determining prevalence of 5.0%. A case was excluded from analysis because of incomplete data. The mean age at diagnosis was 57.1 (±11.2) years. Of the cases analyzed, 11 (84.6%) had palpable tumor and 9 (69.3%) presented lesion of the nipple-areola complex. Only one case was not submitted to mastectomy because she died during neoadjuvant chemotherapy. Radiotherapy was performed in six cases (46.2%); chemotherapy in eleven cases (84.6%); endocrinoterapia in six cases (46.2%). Immunohistochemistry identified five cases (38.5%) with expression of hormone receptors and twelve patients (92.3%) with overexpression of HER2. The overall survival of patients was 61.5 (±13.4) months, and there was no local recurrence after a mean follow-up of 75.8 months. Conclusion: There was a prevalence of Paget's disease of the breast associated with invasive carcinomas with advanced clinical stages; which possibly resulted in overall survival rate lower than that observed in other studies for the region.
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It has recently been proposed to include an immunohistochemical marker of cell proliferation, Ki-67, as an element with which to classify the molecular subtypes of breast cancer. The objective of this study was to evaluate the effect of the introduction of the Ki-67 marker on the molecular classification of breast cancer by immunohistochemistry. This study was performed on 234 cases of invasive ductal carcinoma of the breast submitted to two immunohistochemical classification panels, one including Ki-67 and the other not. The data obtained with the two classifications were correlated with well-established prognostic factors such as histologic grade, the number of lymph nodes affected and tumor size. The molecular classification without Ki-67 identified: 136 cases of luminal A (58.1%), 19 cases of luminal B (8.1%), 27 cases of human epidermal growth-factor receptor 2 overexpressing (11.5%), 27 cases of basal-like (11.5%), and 25 cases of nonbasal-like triple-negative tumors (10.7%). When Ki-67 was included, this situation changed significantly, with the following cases being identified: 72 cases of luminal A (30.8%) and 83 cases of luminal B tumors (35.5%), resulting in a Kappa score of 0.216. Evaluation of correlations between the luminal A and luminal B tumor subtypes and the selected prognostic factors showed a statistically significant difference only when Ki-67 was included and only with respect to histologic grade (p < 0.001). The new classification with Ki-67 significantly altered the prevalence of the luminal A and luminal B subtypes and improved correlation with the histologic grade.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Carcinoma/classificação , Carcinoma/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Gradação de Tumores , Estadiamento de NeoplasiasRESUMO
Adequate management of phyllodes tumors of the breast (PTB) remains a challenge because of the difficulty in correctly establishing preoperative diagnosis. The aim of this study was to evaluate the usefulness of Ki-67, CD10, CD34, p53, CD117, and of the number of mast cells in the differential diagnosis of benign PTB and cellular fibroadenomas (CFs) as well as in the grading of PTB. Fifty-one primary PTB and 14 CFs were examined by immunohistochemistry.When evaluating CD117 expression, higher epithelial expression was present in CF as well as an increased number of mast cells in benign PTB. Stromal expression of Ki-67, CD10, CD34, and p53 were relevant to PTB grading, of which the first 3 showed significance in the distinction of benign and borderline PTB, as well as between benign and malignant PTB. P53 was relevant only for the discrimination between benign and malign PTB. None of the markers showed significance in distinguishing between borderline and malign PTB.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Fibroadenoma/diagnóstico , Mastócitos/patologia , Tumor Filoide/diagnóstico , Adolescente , Adulto , Idoso , Antígenos CD34/análise , Antígenos CD34/biossíntese , Neoplasias da Mama/classificação , Diagnóstico Diferencial , Feminino , Fibroadenoma/classificação , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/biossíntese , Pessoa de Meia-Idade , Neprilisina/análise , Neprilisina/biossíntese , Tumor Filoide/classificação , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/biossíntese , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese , Adulto JovemRESUMO
Chlamydia trachomatis é uma bactéria transmitida sexualmente e uma frequente causa de doença inflamatória pélvica (DIP) que, com sua evolução, pode levar à gravidez ectópica ou a fator de infertilidade túbaria (TFI). Hipóteses sugerem que reações imunes à proteína de choque térmico 60 (HPS60) de Chlamydia trachomatis induz à DIP e à consequente infertilidade. A revisão sistemática foi conduzida utilizando artigos científicos das bases de dados MEDLINE, PubMed e Scopus, com estudos que associavam o aumento do TFI à presença de anticorpos contra HPS60 em mulheres portadoras da bactéria. Foram incluídos 12 estudos. As evidências de 11 estudos caso-controle sugerem a confirmação da associação do TFI com maior produção de anticorpos contra HPS60 de Chlamydia trachomatis. Inversamente ao resultado, foi encontrado um estudo do tipo ensaio clínico controlado randomizado em que os anticorpos contra HPS60 da Chlamydia não foram significamente associados a sequelas por doença inflamatória pélvica. Nossos achados confirmam uma associação entre TFI e anticorpos para HSP60 da Chlamydia trachomatis, mas enfatizamos a necessidade de mais estudos com ensaio clínico controlado e randomizado.
Chlamydia trachomatis is a sexually transmitted bacteria and a common cause of pelvic inflammatory disease (PID); its evolution can lead to ectopic pregnancy or tubal infertility factor (TFI). Hypotheses suggest that immune reactions to heat shock protein 60 (HPS60) of Chlamydia trachomatis induces DIP and, thus, infertility. A systematic review was conducted of scientific articles using MEDLINE, PubMed and Scopus, with studies that linked the increase in the TFI HPS60 presence of antibodies in women with the bacterium. We included 12 studies. Evidence from 11 case-control studies suggest confirmation of the TFI association with increased production of antibodies against HPS60 Chlamydia trachomatis. In contrast to the result, we found a type study randomized controlled trial in which the antibodies of Chlamydia HPS60 were not significantly associated with sequelae of pelvic inflammatory disease. Our findings confirm an association between TFI and antibodies to HSP60 of Chlamydia trachomatis, but emphasize the need for more studies with randomized controlled trial.
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Humanos , Feminino , Gravidez , Chlamydia trachomatis/imunologia , Chlamydia trachomatis/patogenicidade , Infecções por Chlamydia/complicações , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/sangue , /imunologia , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/etiologia , Tubas Uterinas , Gravidez Ectópica/etiologia , Infertilidade Feminina/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
O câncer de mama apresenta alta heterogeneidade clínica, morfológica e biológica, fato esse justificado pela existência de diversas formas moleculares. Diferentes perfis de expressão gênica foram caracterizados, possibilitando a identificação de subtipos moleculares distintos, com fatores prognósticos e alvos terapêuticos específicos. Esta revisão foi conduzida utilizando artigos científicos das bases de dados MEDLINE, SciELO, LILACS e PubMed e teve como objetivo discutir os subtipos moleculares do câncer de mama e suas principais características. O subtipo luminal A apresenta, com relação aos demais, o melhor prognóstico. Na sua maioria, são tumores histologicamente de baixo grau e apresentam resposta inferior à quimioterapia, enquanto, tumores luminais B apresentam maior proliferação e são, muitas vezes, de alto grau histológico. O subtipo superexpressão do receptor tipo 2 do fator de crescimento epidérmico humano (HER2), sem a terapia adjuvante sistêmica, tem menor sobrevida livre de doença e elevada taxa de recorrência, porém se beneficia de terapias alvoespecíficas. O subtipo basaloide demonstra prognóstico mais reservado, associado à menor sobrevida livre de doença e à menor sobrevida global. A anatomia patológica e o teste de imunoistoquímica, através da classificação tumoral, são de fundamental relevância na abordagem terapêutica do carcinoma mamário. Para a atual classificação molecular por imunoistoquímica, recomenda-se a adoção do painel de fatores preditivos receptor de estrogênio (RE), receptor de progesterona (RP) e HER2 para todos os casos, adicionando-se outros marcadores, como o receptor tipo 1 do fator de crescimento epidérmico (EGFR), a citoceratina 5 e o Ki-67
Breast cancer has highly heterogeneous clinical, morphological and biological features, a fact that is justified by the existence of several molecular forms. Different gene expression profiles were characterized, enabling the identification of different molecular subtypes with specific prognostic factors and therapeutic targets. This review was conducted using scientific articles of the databases MEDLINE, SciELO, LILACS and PubMed, and aimed to discuss the molecular subtypes of breast cancer and their main characteristics. The luminal A subtype, when compared with the others, features the best prognosis. Most tumors are histologically low grade and have less response to chemotherapy, while luminal B tumors have high cell proliferation rate and are most often high grade. The enriched subtype to receptor 2 human epidermal growth factor (HER2), without adjuvant systemic therapy, has a lower disease-free survival and higher recurrence rate, but it benefits from target-specific therapies. The basal-like subtype pattern shows poor prognosis associated with lower disease-free survival and shorter overall survival. The pathology and immunohistochemistry test, by tumor classification, are of fundamental importance in the therapeutic management of breast cancer. For the current molecular classification by immunohistochemistry, the adoption of the panel of the predictive factors estrogen receptors (ER), receptors progesterone (PR) and HER2 is recommended for all cases of breast cancer, adding other markers such as epidermal growth factor receptor type 1 (EGFR), the cytokeratin 5 and the Ki-67