RESUMEN
Endometrial cancer is the most common malignancy of the female genital tract, and the incidence and mortality rates from this disease are increasing. Although endometrial carcinoma has been regarded as a tissue-specific disease mediated by female sex steroid pathways, considerable evidence implicates a role for an inflammatory response in the development and propagation of endometrial cancer. We hypothesized that if specific patterns of cytokine expression were found to be predictive of adverse outcome, then selective receptor targeting may be a therapeutic option. This study was therefore undertaken to determine the relationship between cytokine production in primary cell culture and clinical outcome in endometrial adenocarcinoma. Fresh endometrial tissues were fractionated into epithelial and stromal fractions and cultured. After 6-7 days, supernatants were collected and cells enumerated. Batched aliquots were assayed using ELISA kits specific for CSF-1, GMCSF, G-CSF, TNF-α, IL-6, IL-8, and VEGF. Data were compared using ANOVA, Fisher's exact, and log rank tests. Increased epithelial VEGF production was observed more often in tumors with Type 2 variants (p = 0.039) and when GPR30 receptor expression was high (p = 0.038). Although increased stromal VEGF production was detected more often in grade 3 endometrioid tumors (p = 0.050), when EGFR expression was high (p = 0.003), and/or when ER/PR expression was low (p = 0.048), VEGF production did not correlated with overall survival (OS). Increased epithelial CSF-1 and TNF-α production, respectively, were observed more often in tumors with deep myometrial invasion (p = 0.014) and advanced stage (p = 0.018). Increased CSF-1 (89.5% vs. 42.9%, p = 0.032), TNF-α (88.9% vs. 42.9%, p = 0.032, and IL-6 (92.3% vs. 61.5%, p = 0.052) also correlated with low OS. In Cox multivariate models, CSF-1 was an independent predictor of low survival when stratified by grade (p = 0.046) and histology (p = 0.050), and TNF-α, when stratified by histology (p = 0.037). In this study, high CSF-1, TNF-α, and IL-6 production rates identified patients at greatest risk for death, and may signify patients likely to benefit from receptor-specific therapy.
Asunto(s)
Citocinas/metabolismo , Neoplasias Endometriales/metabolismo , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Persona de Mediana Edad , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVES: Hyperglycosylated human chorionic gonadotrophin (hCG) is an hCG variant with extra-large O-linked oligosaccharides, produced by phenotypically invasive cytotrophoblast cells in choriocarcinoma and pregnancy. It is the principal form of hCG produced in the first weeks of gestation. We investigated the importance of hyperglycosylated hCG in pregnancy testing and its detection by current hCG tests. DESIGN AND METHODS: We measured the concentration of hyperglycosylated hCG and total hCG in 512 pregnancies throughout gestation. We assessed and compared the abilities of 14 commonly used commercial laboratory hCG tests and 18 home pregnancy tests to detect regular and hyperglycosylated hCG. RESULTS: Hyperglycosylated hCG is the principal source of hCG-related immunoreactivity in early pregnancy. In the week following missing menses, hyperglycosylated hCG measurements may be more sensitive than regular hCG measurements in detecting pregnancy. Of 14 commercial laboratory hCG tests, 3 appropriately detected hyperglycosylated hCG standard. Of 18 different home pregnancy products 11 poorly or very poorly detected this key antigen. CONCLUSIONS: Hyperglycosylated hCG may be the key molecule in the detection of early pregnancy. However, the majority of tests poorly detected or failed to detect this key antigen. New pregnancy tests are needed that either solely detect hyperglycosylated hCG or equally detect regular hCG and hyperglycosylated hCG.
Asunto(s)
Gonadotropina Coriónica/orina , Pruebas Inmunológicas de Embarazo/métodos , Trofoblastos/metabolismo , Antígenos/orina , Línea Celular Tumoral , Femenino , Glicosilación , Humanos , Embarazo , Sensibilidad y Especificidad , Trofoblastos/inmunologíaRESUMEN
OBJECTIVE: The purpose of this study was to compare gestational trophoblastic disease incidence rates with the use of population-based data. STUDY DESIGN: All incident cases between 1973 and 1997 and live birth, pregnancy, and women at risk were tabulated with the use of data that were derived from the New Mexico Tumor Registry and Vital Records and Health Statistics Annual Reports. Statistical methods included trends analyses, odds ratios, and Poisson regression. RESULTS: Of 939 total cases, 312 non-Hispanic white women, 399 Hispanic white women, 201 American Indian women, and 27 other women were affected. Age-adjusted incidence rates were significantly higher for American Indian women (11.16%) compared with non-Hispanic (3.57%) or Hispanic white women (5.32%); the probability value was <.001. When live birth (1:438 women) and pregnancy (1:486 women) denominators were considered, American Indian women alone were at increased risk, and the ratio increased by 56% over 25 years. American Indian women were also at increased risk for partial mole (relative risk, 4.03; 95% CI, 2.57-6.31), invasive mole (relative risk, 26.7; 95% CI, 7.81-93.14), and choriocarcinoma (relative risk, 6.29; 95% CI, 1.81-22.66) variants. CONCLUSION: American Indians are at increased risk relative to the other predominant ethnic groups in New Mexico. Age-adjusted standardization provided a reproducible measurement that may be applicable across other registries.