Tumores neuroendocrinos de páncreas, Evaluación genética
El síndrome más frecuente que involucra tumores neuroendocrinos de páncreas es el MEN-1. Este está presente en 20 a 25 % de los pacientes con gastrinomas, en 4 % de aquellos con insulinomas y en menos de 3 % en otros tumores neuroendocrinos de páncreas. Casi todos los pacientes con MEN-1 tienen múltiples focos de tumores no funcionales y asintomáticos. Otros, son el síndrome MEN-4 (gen CDKN1) 75,76 y la enfermedad de von Hippel-Lindau (gen VHL) 77. Recientemente, se han caracterizado la deficiencia en el gen MUTYH que se asocia con predisposición a cáncer de colon, cáncer gástrico y otros no gastrointestinales 78, y la mutación de CHEK2, que se asocia con carcinoma de mama y de próstata 79.
Conclusiones
En la actualidad, se cuenta con múltiples biomarcadores para el abordaje inicial y el seguimiento de los tumores neuroendocrinos, y en los gastroenteropancréaticos se tiene la mayor evidencia al respecto. No existe un biomarcador perfecto debido a la complejidad y la heterogeneidad de los tumores neuroendocrinos. Dependemos de la evaluación clínica, radiológica y de la experienciamédica asociada al recurso disponible.
Los biomarcadores séricos y urinarios son difíciles de medir y tienen importante variabilidad preanalítica y analítica. Sin embargo, en los tumores neuroendocrinos funcionales, los biomarcadores séricos tienen mayor rendimiento y son necesarios para establecer el diagnóstico. Un solo estudio, por sí mismo, no brinda la suficiente información diagnóstica, predictiva ni pronóstica. La cromogranina A está sobrevalorada en la práctica clínica y es necesario estandarizarla para nuestra población y conocer muy bien los falsos positivos.
Disponemos de múltiples estudios genéticos, sin embargo, muchos estudios de mutaciones genéticas en tejido y en sangre, no tienen estudios de validación pronóstica ni confirmatoria en los tumores neuroendocrinos de páncreas. Los miRNA han sido evaluados en forma exploratoria y no hay estudios confirmatorios. Las alteraciones epigenéticas han sido evaluadas en pequeños estudios y les falta validación prospectiva. La evaluación multianalítica tiene el potencial de mayor sensibilidad y especificidad en la evaluación inicial y seguimiento, pero requiere revalidación en múltiples circunstancias. Por ahora, se deben practicar estudios genéticos si hay sospecha de síndrome herodofamiliar, sea por el antecedente familiar o por la sintomatología del paciente.
En resumen, una buena historia clínica aunada al conocimiento de la patología, con el uso rutinario del índice Ki-67 y del conteo mitótico, nos ayuda a definir las mejores herramientas para el abordaje del paciente con tumores neuroendocrinos de páncreas y planear el mejor tratamiento y seguimiento.Referencias
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