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Resumen
Existen diferentes metodologías para el estudio de la angiogénesis tumoral, destacando el cálculo de la densidad de microvasos (MVD), técnicas inmunohistoquímicas o moleculares de expresión del factor de crecimiento del endotelio vascular (VEGF) en células tumorales y medición de valores de VEGF enlíquidos tumorales, séricos y ascitis. Aparecen diferencias significativas de MVD, inmunoexpresión VEGF y expresión ARNm-VEGF entre tumores epiteliales ováricos benignos y malignos. En los carcinomas ováricos, se encuentran elevados valores séricos y en ascitis (pg/ml) de VEGF, así como de otros factores angiogénicos, respecto a los controles.
Los valores de MVD, expresión VEGF o concentraciones séricas de VEGF no se correlacionan con los estadios (FIGO) y subtipos histológicos de tumores epiteliales ováricos malignos, interesante circunstancia clínica, al ser el estadio de la enfermedad un clásico factor pronóstico. No existe relación significativa entre MVD y grados histológicos, sin embargo, los tumores G3presentan mayores porcentajes de expresión VEGF y valores séricos de VEGF, comparados con tumores G1-G2.
La mayoría de las publicaciones analizadas realizan variables dicotomizaciones de la MVD que dificultan la comparación de resultados, aunque los tumores ováricos con alta densidad de microvasos aportan peores tasas de supervivencias globales. Si aparece fuerte expresión inmunohistológica VEGF tumoral o aumento de niveles séricos de VEGF, se muestran como variables significativas en la mayoría de los análisis de multivariables, tanto para tasas de supervivencias globales como para supervivencias libres de enfermedad en mujeres portadoras de tumores epiteliales ováricos malignos.
La incipiente terapia antiangiogénica se dirige, en tumores ováricos con alta actividad angiogénica, hacia pequeños focos de células en emigración y proliferación capilar para que éstas sean más vulnerables a la acción de las terapéuticas adyuvantes, pero hasta la fecha, es incierta su eficacia clínica.
Summary
There are several methodologies for the study of tumoral angiogenesis, specially the microvessel density count (MVD), inmunhistochemical analysis of VEGF, VEGF molecular expression on tumours cells and measurement of VEGF levels in tumours fluids and serum levels. There are significatives differences on MVD, VEGF immunostaining and VEGF mRNA expression between benign and malignant epithelial ovarian neoplasms. In ovarian carcinoma, there can be found high VEGF serum and ascites levels (pg/ml), as well as several others angiogenic factors, comparing to controls.
MDV, VEGF expression or VEGF serum levels, are not correlatet with FIGO stages and histological subtypes of epithelial ovarian neoplasms. There is not a significant relation between MVD and histological grades, but tumours have higher percentages ofG VEGF expression and VEGF serum levels compared to G tumours.
Most analyzed publications make several differentMVD and comparate them, which make the comparison of results very difficult. High MVD sometimes make for a worse disease-free and overall survival probability, specially if there is high VEGF expression or high VEGF serum levels because of them being prognostic factors in Cox regression multivariate analysis.
Today’s antiangiogenic therapy is directed, in high angiogenic activity ovarian tumours, towards small cells in emigration and proliferation, so that they become more vulnerables to adjuvant therapies, although their clinical efficiency is still uncertain.
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