Immunohistochemistry expression of human leukocyte antigen-E in thyroid tumors

Células tumorais variantes utilizam-se de diferentes estratégias para evadirem-se do sistema imunológico, tais como a modificação da expressão das moléculas de HLA de classe I. A HLA-E é uma molécula não clássica do sistema HLA considerada ligante de receptores de células Natural Killers (NK) A interação do HLA-E com receptores inibitórios CD94/NKG2A inativa a potente função lítica das células NK favorecendo as células tumorais. Nos últimos anos, com a disponibilidade de novas ferramentas diagnosticas, a incidência de neoplasias da tireoide cresceu gradativamente em diversos países. As neoplasias de tireoide são os tumores endócrinos mais frequentes na casuística mundial com prevalência em mulheres, porém no sexo masculino predominam as formas mais agressivas. Por apresentarem alta heterogeneidade fenotípica, abordar a interação do sistema imunológico diante das neoplasias tireóideas é uma importante ferramenta para explorar o processo de imunovigilância e imunoedição e, consequentemente, o processo de progressão dos tumores da tireoide. Neste estudo, utilizando a técnica de imunoistoquímica foi verificada a expressão da HLA-E em 122 biópsias de neoplasias tireóideas e 21 biopsias de bócio representando as doenças não neoplásicas Ainda a expressão da HLA-E foi correlacionada com a porcentagem de células NK do microambiente tumoral. Assim, resultados significantes foram observados entre lesões neoplásicas e não neoplásicas, porém não foram encontradas diferenças significantes entre neoplasias benigna (adenoma folicular) e maligna (carcinoma diferenciado). A HLA-E também não mostrou correlação com as células NK do infiltrado linfocitário. Portanto nossos dados sugarem que o aumento da HLA-E pode estar associado com a instalação de neoplasias tireóideas, seja de caráter benigno ou malignoTumor cell variants use different strategies to evade the immune system such as modification of the expression of class I HLA molecules. HLA-E is a nonclassical HLA class I molecule considered ligand of receptors of the natural killer cells (NK). The interaction of HLA-E with CD94/NKG2A inhibitory receptons inactivates the potent Iytic function of NK cells favoring the tumor cells. In recent years, with the availability of new diagnostic tools, the incidence of thyroid cancer has increased gradually in various countries. Thyroid neoplasms are the most common endocrine tumors in the worldwide casuistry with a prevalence in women, but in males the most aggressive types predominate. Due to their high phenotypic heterogeneity, to approach the interaction of the immune system in the face of thyroid cancer is an important tool to explore the process of immunosurveillance and immunoedition, and consequently the process of thyroid tumors progression. In this study, using the immunohistochemistry technique it was verified the expression of HLA-E in 122 biopsies of thyroid neoplams and 21 biopsies of goiter representing the nonneoplastic lesions Furthermore, the expression of HLA-E was correlated with the percentage of NK cells in the tumor microenvironment. Thus, significant results were observed between non-neoplastic and neoplastic lesions, but there were no significant differences between benign neoplasms (follicular adenoma) and malignant (differentiated carcinoma). The HLA-E also showed no correlation with NK cells of the Iymphocytic infiltrate Therefore our data suggest that the increase of HLA-E may be associated with the installation of thyroid neoplasms, either of benign or malignant featur

Immunohistochemistry expression of human leukocyte antigen-E in thyroid tumors

Células tumorais variantes utilizam-se de diferentes estratégias para evadirem-se do sistema imunológico, tais como a modificação da expressão das moléculas de HLA de classe I. A HLA-E é uma molécula não clássica do sistema HLA considerada ligante de receptores de células Natural Killers (NK) A interação do HLA-E com receptores inibitórios CD94/NKG2A inativa a potente função lítica das células NK favorecendo as células tumorais. Nos últimos anos, com a disponibilidade de novas ferramentas diagnosticas, a incidência de neoplasias da tireoide cresceu gradativamente em diversos países. As neoplasias de tireoide são os tumores endócrinos mais frequentes na casuística mundial com prevalência em mulheres, porém no sexo masculino predominam as formas mais agressivas. Por apresentarem alta heterogeneidade fenotípica, abordar a interação do sistema imunológico diante das neoplasias tireóideas é uma importante ferramenta para explorar o processo de imunovigilância e imunoedição e, consequentemente, o processo de progressão dos tumores da tireoide. Neste estudo, utilizando a técnica de imunoistoquímica foi verificada a expressão da HLA-E em 122 biópsias de neoplasias tireóideas e 21 biopsias de bócio representando as doenças não neoplásicas Ainda a expressão da HLA-E foi correlacionada com a porcentagem de células NK do microambiente tumoral. Assim, resultados significantes foram observados entre lesões neoplásicas e não neoplásicas, porém não foram encontradas diferenças significantes entre neoplasias benigna (adenoma folicular) e maligna (carcinoma diferenciado). A HLA-E também não mostrou correlação com as células NK do infiltrado linfocitário. Portanto nossos dados sugarem que o aumento da HLA-E pode estar associado com a instalação de neoplasias tireóideas, seja de caráter benigno ou malignoTumor cell variants use different strategies to evade the immune system such as modification of the expression of class I HLA molecules. HLA-E is a nonclassical HLA class I molecule considered ligand of receptors of the natural killer cells (NK). The interaction of HLA-E with CD94/NKG2A inhibitory receptons inactivates the potent Iytic function of NK cells favoring the tumor cells. In recent years, with the availability of new diagnostic tools, the incidence of thyroid cancer has increased gradually in various countries. Thyroid neoplasms are the most common endocrine tumors in the worldwide casuistry with a prevalence in women, but in males the most aggressive types predominate. Due to their high phenotypic heterogeneity, to approach the interaction of the immune system in the face of thyroid cancer is an important tool to explore the process of immunosurveillance and immunoedition, and consequently the process of thyroid tumors progression. In this study, using the immunohistochemistry technique it was verified the expression of HLA-E in 122 biopsies of thyroid neoplams and 21 biopsies of goiter representing the nonneoplastic lesions Furthermore, the expression of HLA-E was correlated with the percentage of NK cells in the tumor microenvironment. Thus, significant results were observed between non-neoplastic and neoplastic lesions, but there were no significant differences between benign neoplasms (follicular adenoma) and malignant (differentiated carcinoma). The HLA-E also showed no correlation with NK cells of the Iymphocytic infiltrate Therefore our data suggest that the increase of HLA-E may be associated with the installation of thyroid neoplasms, either of benign or malignant featur

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering

Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)

Cervical cancer remains persistently the second most common malignancies among women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the estimate is for 18,430 new cases in 2011. Several types of molecular markers have been studied in carcinogenesis including proteins associated with apoptosis such as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and invasive squamous cell carcinomas (SCCs) of the uterine cervix and to verify a possible association with HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG-1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1 expression levels were significantly different between LSILs and HSILs (p = 0,014) and between LSILs and SCCs (p = 0,014). In regards to PARP-1 expression, we found significant differences between the expression levels in HSILs and SCCs (p = 0,022). No association was found between BAG-1 expression and the presence of HPV. However, a significant association was found between PARP-1 expression and HPV positivity in the HSILs group (p = 0,021). In conclusion our research suggests that BAG-1 expression could contribute to the differentiation between LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between HSIL HPV-related and SCC. Further studies are needed to clarify the molecular aspects of the relationship between PARP-1 expression and HPV infection, with potential applications for cervical cancer prediction.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2008/06461-1