Neoplasms with neuroendocrine differentiation: implications of molecular pathology.
Anatomically widespread groups of extra-neural cells produce a spectrum of hormonal oligopeptides and monoamines comparable to those found in the central nervous system. Such cells express the capacity to cleave bioactive oligopeptides from polyprotein precursors, and the designation "neuroendocrine cells" has been widely adopted. Extra-neural cellular proliferations which exhibit the phenotypic manifestations of a neuroendocrine terminal differentiation also occur in a broad topographic distribution. Traditional tumor classifications reflected the wholistic concept of a "diffuse neuroendocrine system" in pathology. Newer results, however, including monoclonal antibody and in situ nucleic acid hybridization studies demonstrate that a variety of otherwise unrelated neoplasms can express the capacity to synthesize "ectopic" monoamines or hormonal oligopeptides. The molecular biological mechanisms which stimulate such cellular proliferations and regulate neuroendocrine expressions must be more diverse and complex than previously supposed. Critical alterations may involve multiple somatic mutations, abnormal gene transpositions or microenvironmental factors which could condition polyprotein gene transcription or post-transcriptional regulation. Accordingly, convergent patterns of neuroendocrine terminal differentiation in proliferative lesions and familial tumor complexes need not be pathogenetically homogenous. Molecular pathologic techniques now offer the potential to individualize diagnostic categories, and ultimately will facilitate more accurate clinical assessments of genetic risks, biologic progression, and therapeutic trials.
Grimley
P M
PM
Department of Pathology, F. Edward Herbert Medical School, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Albores-Saavedra
J
J
D000911:Antibodies, Monoclonal; D006801:Humans; D009369:Neoplasms / Q000145:classification / Q000209:etiology / Q000473:pathology*; D009490:Neurosecretory Systems; D009693:Nucleic Acid Hybridization
D000911:Antibodies, Monoclonal