MOLECULAR APPROACHES TO NEUROENDOCRINE PATHOLOGY

Prognosis of many tumour types is influenced by the degree of neuroend ocrine differentiation. Neuroendocrine tumours produce bioactive pepti des and amines that can have major disruptive effects on physiology. I n the past, investigation of neuroendocrine pathology has relied upon traditional histological staining methods and morphological analysis a t light and electron microscopic level. While these methods are still invaluable, the use of immunocytochemical techniques has revolutionise d the diagnosis and understanding of neuroendocrine tumours, allowing precise identification of tumour types by means of antibodies to gener al neuroendocrine markers and tumour-specific antigens. However, the h istogenesis/oncogenesis of neuroendocrine neoplasia cannot be understo od by characterising the tumour products alone. Molecular technology h as made possible investigation of gene expression by in situ hybridisa tion, electrophoresis and Northern or Southern blotting, and highly sp ecific and sensitive techniques such as the polymerase chain reaction. Where gene expression and gene product storage are poorly correlated, molecular pathology provides vital information to aid diagnosis. Unde rstanding of genetic factors involved in the familial neuroendocrine s yndromes such as multiple neuroendocrine neoplasia (MEN) has improved. Oncogenes, tumour-suppressor genes and transcription factors have bee n identified. The factors controlling cell proliferation, growth and p rogression of tumours can be investigated at molecular level. Expressi on of amidating enzymes along with bioactive products including growth factors raises the question of whether tumour growth can be controlle d or prevented by inhibition of amidating enzymes that activate the gr owth factors.