NSE measurements are utilized in monitoring therapy and progress in patients with tumor diseases, particularly small cell bronchial carcinoma and neuroblastoma.
The glycolytic enzyme enolase (2‑phospho‑D‑glycerate hydrolase, EC 4.2.1.11, molecular weight approximately 80 kDa) occurs in a variety of dimeric isoforms comprising three immunologically different subunits termed α, β, and γ. The α‑subunit of enolase occurs in numerous types of tissue in mammals, whereas the β‑subunit is found mainly in the heart and in striated musculature. The enolase isoforms αγ and γγ, which are referred to as neuron-specific enolase (NSE) or γ‑enolase, are primarily detectable in high concentrations in neurons and neuro-endocrine cells as well as in tumors originating from them.
Bronchial carcinoma: NSE is described as the marker of first choice in the monitoring of small cell bronchial carcinoma, whereas CYFRA 21‑1 is superior to NSE for non-small cell bronchial carcinoma.
Elevated NSE concentrations are found in 60‑81 % of cases of small cell bronchial carcinoma.
For NSE there is no correlation to the site of metastasis or to cerebal metastasis, but there is good correlation to the clinical stage, i.e. the extent of the disease.
In response to chemotherapy there is a temporary rise in the NSE level 24‑72 hours after the first therapy cycle as a result of cytolysis of the tumor cells. This is followed within a week or by the end of the first therapy cycle by a rapid fall in the serum values (which were elevated prior to therapy). By contrast, non-responders to therapy display levels which are constantly elevated or fail to fall into the reference range. During remission, 80‑96 % of the patients have normal values. Rising NSE values are found in cases of relapse. The rise occurs in some cases with a latent period of 1‑4 months, is often exponential (with a doubling time of 10‑94 days) and correlates with the survival period. NSE is useful as a single prognostic factor and activity marker during the monitoring of therapy and the course of the disease in small cell bronchial carcinoma: diagnostic sensitivity 93 %, positive predictive value 92 %.
Neuroblastoma: NSE serum values above 30 ng/mL are found in 62 % of the affected children. The medians rise in accordance with the stage of the disease. There is a significant correlation between the magnitude or frequency of pathological NSE values and the stage of disease; there is an inverse correlation with illness-free survival.
Apudoma: In 34 % of the cases elevated NSE values (> 12.5 ng/mL) are found in serum.
Seminoma: 68‑73 % of the patients have a clinically significant NSE elevation. There is a utilizable correlation with the clinical course of the disease.
Other tumors: Non-pulmonary malignant diseases show values above 25 ng/mL in 22 % of the cases (carcinomas in all stages). Brain tumors such as glioma, meningioma, neurofibroma, and neurinoma are only occasionally accompanied by elevated serum NSE values. In primary brain tumors or brain metastasis and in malignant melanoma and phaeochromocytoma, elevated NSE values can occur in the CSF (cerebrospinal fluid). Increased NSE concentrations have been reported for 14 % of organ-restricted and 46 % of metastasizing renal carcinomas, with a correlation to the grade as an independent prognosis factor.
Benign disease: Elevated serum NSE concentrations (> 12 ng/mL) have been found in patients with benign pulmonary diseases and cerebral diseases. Elevated values, mainly in the liquor, have been found in cerebrovascular meningitis, disseminated encephalitis, spinocerebellar degeneration, cerebral ischemia, cerebral infarction, intracerebral hematoma, subarachnoid hemorrhage, head injuries, inflammatory brain diseases, organic epilepsy, schizophrenia, and Jakob‑Creutzfeld disease.