RESUMO

BACKGROUND: The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence. RESULTS: MMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (-) in stroma displayed a significant reduction of survival. CONCLUSIONS: The presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.

Assuntos

Carcinoma Epitelial do Ovário/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Ovarianas/patologia , Receptores Androgênicos/metabolismo , Adulto , Carcinoma Epitelial do Ovário/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Prognóstico , Estudos Retrospectivos , Células Estromais/metabolismo , Células Estromais/patologia , Análise de Sobrevida

RESUMO

BACKGROUND: Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. RESULTS: The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95 % CI 1.08-4.84, P = 0.032. CONCLUSIONS: Clinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients.

Assuntos

Biomarcadores Tumorais , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem

RESUMO

Contenido: 1.Introducción. 2.Consideraciones preliminares. 3.Conceptos y definiciones básicas del control de tránsito. 4.Elementos de capacidad vial. 5.Ciclo, reparto, fases y coordinación de semáforos. 6.Análisis y evaluación del actual sistema. 7.Aplicación del proyecto. 8.Conclusiones. 9.Bibliografía.