GRP78 levels, regional fat distribution and endometrial cáncer / Niveles de GRP78, distribución regional del tejido adiposo y cáncer endometrial

Background: The association of obesity with endometrial cancer is supported by the presence of endoplasmic reticulum (ER) stress in the adipocyte. Glucose-regulated protein 78 (GRP78) is a marker for ER stress. This protein is a central regulator of ER stress due to its major anti-apoptotic role. It plays an important role in tumor development, progression and chemoresistance. Aim: To look for an association between android and gynoid obesity, plasma GRP78 levels and endometrial cancer. Material and methods: Forty four patients with endometrial cancer aged 72 ± 6 years and 44 healthy women aged 55 ± 9 years were studied. Android and gynoid fat distribution were determined by dual X-ray absorptiometry and plasma GRP78 levels were measured. Results: GRP78 plasma levels were significantly higher in patients with endometrial cancer as compared to the control group. Android fat distribution had a positive correlation with plasma GRP78 levels (p<0.01). Gynoid fat had a negative correlation with plasma GRP78 levels (p<0.01). Conclusions: GRP78 levels are associated with the distribution of adipose tissue and are higher in patients with endometrial cancer.

Antecedentes: La asociación de obesidad con cáncer endometrial puede depender de la presencia de estrés del retículo endoplásmico (RE) en el adipocito. La proteína 78 regulada por glucosa (GRP78) es un marcador de estrés del RE. Esta proteína regula el estrés de RE gracias a su rol antiaopoptótico. Ella juega un rol en el desarrollo, progresión y quimio-resistencia de tumores. Objetivo: Buscar una asociación entre obesidad androide o ginoide, niveles plasmáticos de GRP78 y cáncer endometrial. Material y métodos: Se estudiaron 44 mujeres con cáncer endometrial de 72 ± 6 años and 44 mujeres sanas de 55 ± 9 años. La distribución androide o ginoide de la grasa fue determinada por densitometría radiológica de doble fotón (DEXA) y se midieron los niveles plasmáticos de GRP78. Resultados: Los niveles de GRP78 fueron significativamente más altos en mujeres con cáncer endometrial. Se observó una correlación positiva entre la distribución de grasa androide y los niveles de GRP78 (p< 0.01). Se observó una correlación negativa entre distribución de grasa ginoide y niveles de GRP78. Conclusiones: Los niveles de GRP78 se correlacionan con la distribución del tejido adiposo y son mayores en mujeres con cáncer endometrial.

Assessment of Mean Vessel Density and Angiogenesis in Endometrial Carcinomas.

Objective: To evaluate the role of angiogenesis in tumor growth by the assessment of mean vessel density and to quantify angiogenesis as an important variable in endometrial cancers. Material and Methods: 53 cases of endometrial malignancies (epithelial tumors-36 cases and metastatic tumors-17 cases), were analysed for histological types, grades and features like depth of invasion and vascular invasion. Microvessel counts were performed by examining the microvessels thoroughly in terms of count, morphology and density after staining the tissues by hematoxylin & eosin stain, reticulin and immunostain (Antifactor VIII Ag). Results: On H&E stain - Microvessel density (MVD) in endometrial malignancy ranged from 3.0 - 13.5 and mean MVD was 8.78. On Reticulin stain - MVD ranged from 3.5 - 15.2 and mean MVD was 9.76. Antifactor VIII sections showed very small microvessels or even single endothelial cells with the highest total counts and the MVD ranged from 6.5- 16.8 with Mean MVD of 11.7. The counts increased with the grade of the tumor in the absence of necrosis or haemorrhage. MVD counts also increased with the stage, being 8.12 in Stage I disease, 8.65 in Stage II and 10.8 in stage III disease. Atypical hyperplasia was found to be associated with epithelial tumors in 8 cases, making it a significant finding. Conclusion: Role of angiogenesis assumes greater significance with increasing severity of lesions, higher grade and stage of the tumor and seems to have an important diagnostic and prognostic significance.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasiaor adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Resultados epidemiológicos e experimentais apontam para o envolvimento dos radicais derivados do oxigênio na patogênese das moléstias ginecológicas, assim como no desenvolvimento do câncer. O objetivo do presente estudo foi o de examinar as alterações nas atividades e níveis de Cu/Zn superóxido dismutase (CuZnSOD) e hidroperóxidos lipídicos (LOOH)no sangue e tecido endometrial de pacientes diagnosticados com mioma uterino, pólipo endometrial, hiperplasia simplex, hiperplasia complex e adenocarcinoma do endométrio. Os resultados de nosso estudo mostraram atividades de SOD diminuídas e nível de SOD proteína inalterado no sangue de todos os pacientes examinados em comparação a indivíduos saudáveis. Diminuição de ambos, atividade de SOD e nível protéico, foram encontrados no endométrio de pacientes com hiperplasia simplex, hiperplasia complex e adenocarcinoma em comparação às mulheres com pólipos e/ou mioma. O nível de LOOH estava elevado em ambos os tecidos de pacientes com hyperplasia e adenocarcinoma em comparação a indivíduos saudáveis ou pacientes com diagnóstico benigno. Nossos resultados sugerem que um decréscimo na atividade e nível protéico de SOD, assim como um incremento no nível de LOOH, em pacientes com desordens ginecológicas, tornam esses pacientes mais susceptíveis ao dano oxidativo causado pelas espécies reativas de oxigênio (ROS). Um desequilíbrio na formação de ROS e no nível de SOD pode ser importante na patogênese e/ou perpetuação do dano tecidual em pacientes ginecológicos. Desde que existe evidência de que SOD pode ser um alvo para terapia de câncer, nossos resultados fornecem uma base para futura pesquisa e opções para aplicações clínicas.

Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium

Oxidative stress is considered to be involved in pathogenesis of many disorders of the female genital tract. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of uterine diseases in order to evaluate the extent of oxidative stress in blood of such patients. Blood samples of healthy subjects and gynecological patients were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides. The results show that alterations of measured parameters vary with the enzyme type and diagnosis. However, both reduction in antioxidants and elevation of lipid peroxidation were observed in general. Lipid hydroperoxides level was negatively correlated to superoxide dismutase and glutathione peroxidase activities, as well as positively correlated to catalase activity. In addition, the lipid hydroperoxides/ glutathione peroxidase ratio was found to be increased, according to the type of uterine disease. The obtained results show that perturbation of antioxidant status is more pronounced in blood of patients with premalignant (hyperplastic) and malignant (adenocarcinoma) lesions, compared to those with benign uterine changes such as polypus and myoma.

Esteróides sexuais e gonadotrofinas em mulheres com e sem carcinoma de endométrio: um estudo clínico comparativo / Endogenous sexual steroids and gonadotrophins in women with or without endometrial carcinoma: a comparative clinical study

Objetivo: analisar os níveis dos esteróides sexuais endógenos e gonadotrofinas em mulheres com e sem câncer de endométrio. Métodos: foi realizado estudo clínico-comparativo com 20 mulheres na pós-menopausa com câncer de endométrio e 20 mulheres na pós-menopausa, sem câncer de endométrio. A idade, o tempo de menopausa e o índice de massa corpórea foram utilizados como variáveis de emparelhamento. Os níveis plasmáticos dos esteróides sexuais endógenos froam medidos por métodos de radioimunoensaio e imunoenzimático. Para análise estatística utilizamos o teste "t" de Student. Resultados: os níveis de androstenediona (A), testosterona total (t) e testosterona livre (TL) foram mais elevados nas mulheres com câncer de endométrio e os níveis de hormônio luteinizante (LH) foram significativamente menores nessas mulheres. Também observados que a razão (E1/A) mostrou valores significativamente menores no grupo de mulheres com câncer, ao passo que a razão E2/E1) não apresentou diferenças nos dois grupos. Conclusões: destacamos a potencialidade dos esteróides sexuais e gonadotrofinas na gênese do adenocarcinoma de endométrio em mulheres na pós-menopausa.