Clinical Information

Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Enolase exists in the form of several tissue-specific isoenzymes, consisting of homo or heterodimers of 3 different monomer-isoforms (alpha, beta, and gamma). Neuron-specific enolase (NSE) is a 78 kDa gamma-homodimer and represents the dominant enolase-isoenzyme found in neuronal and neuroendocrine tissues. Its levels in other tissues, except erythrocytes, are negligible. The biological half-life of NSE in body fluids is approximately 24 hours.

Due to this organ-specificity, concentrations of NSE in serum or, more commonly, cerebrospinal fluid (CSF) are often elevated in diseases that result in relative rapid (hours/days to weeks rather than months to years) neuronal destruction. Measurement of NSE in serum or CSF can therefore assist in the differential diagnosis of a variety of neuron-destructive and neurodegenerative disorders. The most common application is in the differential diagnosis of dementias, where elevated CSF concentrations support the diagnosis of rapidly progressive dementias, such as Creutzfeldt-Jacob Disease. NSE may also have utility as a prognostic marker in neuronal injury. For example, there is increasing evidence that elevated serum NSE levels correlate with a poor outcome in coma, particularly when caused by hypoxic insult.

Neuron-specific enolase is frequently overexpressed by neural crest-derived tumors. Up to 70% of patients with small cell lung carcinoma (SCLC) have elevated serum NSE concentrations at diagnosis. Approximately 90% of patients with advanced SCLC will have serum levels above the healthy reference range. Other neuroendocrine tumors with frequent expression of NSE include carcinoids (up to 66% of cases), islet cell tumors (typically <40% of cases), and neuroblastoma (exact frequency of NSE expression unknown). NSE levels in NSE-secreting neoplasms correlate with tumor mass and tumor metabolic activity. High levels have, therefore, some negative prognostic value. Falling or rising levels are often correlated with tumor shrinkage or recurrence, respectively.