Molecular approaches to neuroendocrine pathology

Prognosis of many tumour types is influenced by the degree of neuroendocrine differentiation. Neuroendocrine tumours produce bioactive peptides and amines that can have major disruptive effects on physiology. In the past, investigation of neuroendocrine pathology has relied upon traditional histological staining methods and morphological analysis at light and electron microscopic level. While these methods are still invaluable, the use of immunocytochemical techniques has revolutionised the diagnosis and understanding of neuroendocrine tumours, allowing precise identification of tumour types by means of antibodies to general neuroendocrine markers and tumour-specific antigens. However, the histogenesis/oncogenesis of neuroendocrine neoplasia cannot be understood by characterising the tumour products alone. Molecular technology has made possible investigation of gene expression by in situ hybridisation, electrophoresis and Northern or Southern blotting, and highly specific 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. Understanding of genetic factors involved in the familial neuroendocrine syndromes such as multiple neuroendocrine neoplasia (MEN) has improved. Oncogenes, tumour-suppressor genes and transcription factors have been identified. The factors controlling cell proliferation, growth and progression of tumours can be investigated at molecular level. Expression of amidating enzymes along with bioactive products including growth factors raises the question of whether tumour growth can be controlled or prevented by inhibition of amidating enzymes that activate the growth factors.